Pubblicazioni Dr Mario Preti - Studio ginecologico Torino

1. J Low Genit Tract Dis. 2021 Jan 1;25(1):57-70. doi: 10.1097/LGT.0000000000000572.

Diagnostic Criteria for Differentiated Vulvar Intraepithelial Neoplasia and Vulvar Aberrant Maturation.

Heller DS(1), Day T(2), Allbritton JI(3), Scurry J, Radici G(4), Welch K(5), Preti M(4); ISSVD Difficult Pathologic Diagnoses Committee.

Author information:

(1)Rutgers-New Jersey Medical School, Newark, NJ.

(2)Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia.

(3)University of Maryland School of Medicine, Baltimore, MD.

(4)University of Torino, Torino, Italy.

(5)University of Michigan, Ann Arbor, MI.

OBJECTIVE: The aim of the study was to describe the features required for diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN) and vulvar aberrant maturation (VAM).

MATERIALS AND METHODS: The International Society of the Study of Vulvovaginal Diseases tasked the difficult pathologic diagnoses committee to develop consensus recommendations for clinicopathologic diagnosis of vulvar lichen planus, lichen sclerosus, and dVIN. The dVIN subgroup reviewed the literature and formulated diagnostic criteria that were reviewed by the committee and then approved by the International Society of the Study of Vulvovaginal Diseases membership.

RESULTS: Differentiated vulvar intraepithelial neoplasia is the immediate precursor of human papillomavirus (HPV)-independent vulvar squamous cell carcinoma and shows a spectrum of clinical and microscopic appearances, some overlapping with HPV-related neoplasia. The histopathologic definition of dVIN is basal atypia combined with negative or nonblock-positive p16 and basal overexpressed, aberrant negative, or wild-type p53. The most common pattern of dVIN is keratinizing with acanthosis, aberrant rete ridge pattern, and premature maturation. The morphologic spectrum of keratinizing dVIN includes hypertrophic, atrophic, acantholytic, and subtle forms. A few dVIN cases are nonkeratinizing, with basaloid cells replacing more than 60% of epithelium. Vulvar aberrant maturation is an umbrella term for lesions with aberrant maturation that arise out of lichenoid dermatitis and lack the basal atypia required for dVIN.

CONCLUSIONS: Evaluation of women at risk for dVIN and VAM requires a collaborative approach by clinicians and pathologists experienced in vulvar disorders. Close surveillance of women with lichen sclerosus and use of these recommendations may assist in prevention of HPV-independent squamous cell carcinoma through detection and treatment of dVIN and VAM.

DOI: 10.1097/LGT.0000000000000572

PMCID: PMC7748053

PMID: 33105449

Conflict of interest statement: The authors have declared they have no conflicts of interest.

2. BMC Cancer. 2020 Oct 7;20(1):972. doi: 10.1186/s12885-020-07452-6.

Risk of HPV-related extra-cervical cancers in women treated for cervical intraepithelial neoplasia.

Preti M(1), Rosso S(2), Micheletti L(1), Libero C(1), Sobrato I(2), Giordano L(3), Busso P(2), Gallio N(4), Cosma S(1), Bevilacqua F(1), Benedetto C(1).

Author information:

(1)Department of Surgical Sciences University of Torino, Via Ventimiglia 3, 10126, Torino, Italy.

(2)Piedmont Cancer Registry – CPO, Torino, Italy.

(3)Cancer Prevention Center of Piedmont, Torino, Italy.

(4)Department of Surgical Sciences University of Torino, Via Ventimiglia 3, 10126, Torino, Italy. niccolo.gallio@edu.unito.it.

BACKGROUND: The aim was to estimate the risk of subsequent extra-cervical Human Papillomavirus (HPV) related cancer in patients surgically treated for high grade cervical intraepithelial neoplasia (CIN 2-3). This is the first study in Italy investigating the occurrence of extra-cervical tumors in this cohort of patients.

METHODS: 3184 patients surgically treated for CIN2-3 since 1992 at the Department of Surgical Sciences of University of Torino were considered. The risk of HPV-related cancer was calculated as Standardized Incidence Ratio (SIR), using as expected values tumour age specific incidence of resident population.

RESULTS: 173 second primary cancer (SCPs) were identified. SIR to develop cancer after treatment for CIN2-3 was 2.2 (CI 95% 1.89-2.50). Among these occurrences, 10 are in HPV related sites: 1 anus (SIR = 1.8; 0.04-10.0), 3 vagina (SIR = 12.4; 2.56-36.3), 1 vulva (SIR = 1.7; 0.04-9.59), 5 oropharynx (SIR = 8.5; 2.76-19.8). Significant risk has been also recorded for pulmonary (SIR = 3.1; 0.70-5.27) and bladder (SIR = 4.05; 1.10-10.56), with smoking as possible cofactor. We also found increased risk for breast (SIR = 2.4; 2.07-2.84) and ovarian cancers (SIR = 2.1; 1.13-3.49), probably due to an higher adherence to spontaneous and programmed screening programs.

CONCLUSIONS: Our study supports the hypothesis of an increased risk of HPV-related tumours for CIN treated patients, mostly for CIN3. It is conceivable the need of early diagnosis for these cancers in this higher-risk populations.

DOI: 10.1186/s12885-020-07452-6

PMCID: PMC7542855

PMID: 33028248

Conflict of interest statement: The authors declare that they have no competing interests.

3. J Low Genit Tract Dis. 2020 Oct;24(4):387-391. doi: 10.1097/LGT.0000000000000559.

Management of Vulvar Cancer Precursors: A Survey of the International Society for the Study of Vulvovaginal Disease.

Green N(1), Adedipe T, Dmytryshyn J, Preti M, Selk A.

Author information:

(1)1Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada 2Hull University Teaching Hospital NHS Trust, Hull, United Kingdom 3Department of Surgical Sciences, University of Torino, Torino, Italy 4Department of Gynecology, Women’s College Hospital, Toronto, Ontario, Canada.

OBJECTIVE: The aim of the study was to determine how experts treat vulvar high-grade squamous intraepithelial neoplasia (VHSIL) and differentiated vulvar intraepithelial neoplasia (dVIN).

METHOD: A 26-question survey was designed through a literature review, reviewed by the Survey Committee of the International Society for the Study of Vulvovaginal Disease (ISSVD), and distributed to all ISSVD members via e-mail in January 2019.

RESULTS: Overall, 90 of 441 physician members consented to participate and 78 of 90 were eligible to complete the survey. Most respondents were gynecologists (77%), followed by dermatologists (12%). Forty-five percent responded that their pathology was being reported using the 2015 ISSVD terminology of vulvar squamous intraepithelial lesions. The most common first-line treatments were as follows: unifocal VHSIL-excision (65%), multifocal VHSIL-imiquimod 5% (45%), VHSIL in a hair-bearing area-excision (69%), and clitoral disease-imiquimod 5% (47%). In the recurrent VHSIL, excision was favored (28%), followed by imiquimod 5% (26%) and laser (19%). Differentiated vulvar intraepithelial neoplasia was most often first treated with excision (82%), and more patients were referred to gynecologic oncology. Most patients were seen in follow-up at 3 months (range: 1 week-6 months). Sixty-seven respondents provided 26 different ways to follow treated patients, which were most commonly every 6 months for 2 years and then yearly (25%), followed by every 6 months indefinitely (18%).

CONCLUSIONS: Treatment of VHSIL and dVIN varies among vulvar experts with excision being the most common treatment, except in multifocal VHSIL where imiquimod is commonly used. There is wide variation in how patients are followed after treatment.

DOI: 10.1097/LGT.0000000000000559

PMID: 32986387

4. Eur Rev Med Pharmacol Sci. 2020 Aug;24(16):8510-8528. doi: 10.26355/eurrev_202008_22648.

Extending Human Papillomavirus (HPV) vaccination beyond female adolescents and after treatment for high grade CIN: the Italian HPV Study Group (IHSG) review and position paper.

Origoni M(1), Cristoforoni P, Mariani L, Costa S, Preti M, Sandri MT, Preti EP, Ghelardi A, Perino A.

Author information:

(1)Department of Gynecology and Obstetrics, Vita Salute San Raffaele University School of Medicine, Milan, Italy. antonio.perino@unipa.it.

Human PapillomaVirus (HPV) vaccination has been introduced in recent years in clinical practice as the most effective primary prevention strategy for cervical cancer and HPV-induced lesions, either pre-malignant or benign. Since its introduction, HPV vaccination has been progressively demonstrated as extremely effective in preventing extra-genital and male diseases also; furthermore, non only adolescents but adult subjects have been investigated and reported as positively responding to vaccine immunostimulation. More recently, effectiveness of post-treatment vaccine administration has been preliminarily investigated with very promising results in terms of decreased recurrences. On this basis, we report an Italian-focused picture of the state of the art and take a position in favour of the extension of HPV vaccination to male adolescents, to older age groups and to already treated subjects.

DOI: 10.26355/eurrev_202008_22648

PMID: 32894557

5. J Gynecol Obstet Hum Reprod. 2020 Aug 17;50(3):101890. doi: 10.1016/j.jogoh.2020.101890. Online ahead of print.

Clarification about vulvar cancer precursor lesions.

Vieira-Baptista P(1), Stockdale CK(2), Preti M(3), Heller D(4), Bornstein J(5).

Author information:

(1)Hospital Lusíadas Porto, Porto, Portugal; Lower Genital Tract Unit, Centro

Hospitalar de São João, Porto, Portugal; LAP, Unilabs, Porto, Portugal. Electronic address: pedrovieirabaptist@gmail.com.

(2)Department of Obstetrics and Gynecology, University of Iowa Carver College of Medicine, Iowa City, IA, USA. Electronic address: colleen-stockdale@uiowa.edu.

(3)Department of Surgical Sciences, University of Turin, Turin, Italy. Electronic address: mario.preti@unito.it.

(4)Department of Pathology, Rutgers-New Jersey Medical School, Newark, NJ, USA. Electronic address: hellerds@njms.rutgers.edu.

(5)Obstetrics and Gynecology Department, Galilee Medical Center, Nahriya, Israel; Azrieli Faculty of Medicine, Bar Ilan University, Ramat Gan, Israel. Electronic address: mdjacob@gmail.com.

DOI: 10.1016/j.jogoh.2020.101890

PMID: 32818663

6. Cancers (Basel). 2020 Aug 4;12(8):2156. doi: 10.3390/cancers12082156.

Brain Metastases from Ovarian Cancer: Current Evidence in Diagnosis, Treatment, and Prognosis.

Borella F(1), Bertero L(2), Morrone A(2), Gambella A(2), Bovetti M(1)(3), Cosma S(1)(3), Carosso A(1), Katsaros D(1)(3), Gemmiti S(1)(3), Preti M(1)(3), Valabrega G(4)(5), Scotto G(4)(5), Cassoni P(2), Benedetto C(1)(3).

Author information:

(1)Department of Surgical Sciences, University of Turin, 10126 Turin, Italy.

(2)Pathology Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy.

(3)Obstetrics and Gynecology Unit 1, Sant’ Anna Hospital, University of Turin, 10126 Turin, Italy.

(4)Candiolo Cancer Institute, FPO-IRCCS, Strada Provinciale 142 Km 3.95, Candiolo, 10060 Torino, Italy.

(5)Department of Oncology, University of Turin, Candiolo, 10060 Torino, Italy.

With this review, we provide the state of the art concerning brain metastases (BMs) from ovarian cancer (OC), a rare condition. Clinical, pathological, and molecular features, treatment options, and future perspectives are comprehensively discussed. Overall, a diagnosis of high-grade serous OC and an advanced disease stage are common features among patients who develop brain metastases. BRCA1 and BRCA2 gene mutations, as well as the expression of androgen receptors in the primary tumor, are emerging risk and prognostic factors which could allow one to identify categories of patients at greater risk of BMs, who could benefit from a tailored follow-up. Based on present data, a multidisciplinary approach combining surgery, radiotherapy, and chemotherapy seem to be the best approach for patients with good performance status, although the median overall survival (<1 year) remains largely disappointing. Hopefully, novel therapeutic avenues are being explored, like PARP inhibitors and immunotherapy, based on our improved knowledge regarding tumor biology, but further investigation is warranted.

DOI: 10.3390/cancers12082156

PMCID: PMC7464214

PMID: 32759682

Conflict of interest statement: G. Valabrega has received personal fees from Roche, AstraZeneca, Tesaro, PharmaMar and Amgen. The remaining authors have no conflicts of interest to declare.

7. J Med Virol. 2020 Jul 7:10.1002/jmv.26267. doi: 10.1002/jmv.26267. Online ahead of print.

The “scar” of a pandemic: Cumulative incidence of COVID-19 during the first trimester of pregnancy.

Cosma S(1), Borella F(1), Carosso A(1), Sciarrone A(2), Cusato J(3), Corcione S(4)(5), Mengozzi G(6), Preti M(1), Katsaros D(1), Di Perri G(7), Benedetto C(1).

Author information:

(1)Gynecology and Obstetrics 1, Department of Surgical Sciences, School of Health and Science, University of Turin, Turin, Italy.

(2)Obstetrics-Gynecological Ultrasound and Prenatal Diagnosis Unit, Department of Obstetrics and Gynecology, School of Health and Science, Turin, Italy.

(3)Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, Turin, Italy.

(4)Division of Infectious Diseases, Department of Medical Sciences, School of Health and Science, University of Turin, Turin, Italy.

(5)Division of Geographic Medicine and Infectious Diseases, Tufts School of Medicine, Boston, Massachusetts.

(6)Department of Public Health and Pediatric Sciences, Diagnostic Hemostasis Laboratories, School of Health and Science, Turin, Italy.

(7)Unit of Infectious Diseases, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, Turin, Italy.

Congenitally- or perinatally-acquired viral infections can be harmful to the fetus but data are limited about prevalence and outcomes of coronavirus disease 2019 (COVID-19) disease during the first trimester of pregnancy. We report epidemiologic data from a study investigating a cohort of women who became pregnant just before or during the COVID-19 pandemic. We recruited 138 consecutive pregnant women attending for first trimester screening (11-13 weeks of gestation) at Sant’Anna Hospital, Turin, Piedmont, Italy, during the plateau and the falling phase of the COVID-19 epidemic curve. Patients were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin M/immunoglobulin G antibody levels and SARS-CoV-2 detection in sera and nasopharyngeal swab samples. COVID-19 cumulative incidence during the first trimester was of 10.1% with high prevalence of asymptomatic patients (42.8%). Similar to the course of the disease in non pregnant adults, 80% to 90% of infections were not severe.The prevalence of reported symptoms was four-fold higher in SARS-CoV-2 positive patients (57%) than in those negative (13%) (P < .001), suggesting that direct self-testing should open doors to confirmatory testing for COVID-19. Our findings support the need for COVID-19 screening in early pregnancy in epidemic areas to plan materno-fetal health surveillance programs.

DOI: 10.1002/jmv.26267

PMCID: PMC7361535

PMID: 32633869

8. Gynecol Oncol. 2020 Jun;157(3):656-663. doi: 10.1016/j.ygyno.2020.03.013. Epub 2020 Apr 7.

Incidence trends of vulvar squamous cell carcinoma in Italy from 1990 to 2015.

Mancini S(1), Bucchi L(1), Baldacchini F(1), Giuliani O(1), Ravaioli A(2), Vattiato R(1), Preti M(3), Tumino R(4), Ferretti S(5), Biggeri A(6), Brustolin A(7), Boschetti L(8), Caiazzo AL(9), Caldarella A(10), Cesaraccio R(11), Cirilli C(12), Citarella A(13), Filiberti RA(14), Fusco M(15), Galasso R(16), Gatti L(17), Lotti FL(18), Magoni M(19), Mangone L(20), Masanotti G(21), Mazzoleni G(22), Mazzucco W(23), Melcarne A(24), Michiara M(25), Pesce P(26), Piffer S(27), Pinto A(28), Rognoni M(29), Rosso S(30), Rugge M(31), Sampietro G(32), Scalzi S(33), Scuderi T(34), Tagliabue G(35), Tisano F(36), Toffolutti F(37), Vitarelli S(38), Falcini F(39); AIRTUM Working Group.

Author information:

(1)Romagna Cancer Registry, Romagna Cancer Institute, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Forlì, Italy.

(2)Romagna Cancer Registry, Romagna Cancer Institute, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Forlì, Italy. Electronic address: alessandra.ravaioli@irst.emr.it.

(3)Department of Obstetrics and Gynaecology, University of Torino, Torino, Italy.

(4)Cancer Registry and Histopathology Department, Provincial Health Authority (ASP), Ragusa, Italy.

(5)University of Ferrara, Local Health Authority, Ferrara, Italy.

(6)Department of Statistics, Computer Science, Applications G. Parenti, University of Florence, Florence, Italy.

(7)Unit of Epidemiology and Cancer Registry, Local Health Authority, Viterbo, Italy.

(8)Pavia Cancer Registry, Public Health Agency of Pavia, Pavia, Italy.

(9)Cancer Registry of Local Health Authority Salerno, Salerno, Italy.

(10)Tuscany Cancer Registry, Clinical and Descriptive Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy.

(11)Sassari Cancer Registry, Azienda Regionale per la Tutela della Salute – ATS, Sassari, Italy.

(12)Modena Cancer Registry, Public Health Department, Local Health Authority, Modena, Italy.

(13)Cancer Registry, Department of Prevention, Unit of Epidemiology, Local Health Authority, Benevento, Italy.

(14)Liguria Cancer Registry, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

(15)Napoli 3 Sud Cancer Registry, Napoli, Italy.

(16)Unit of Regional Cancer Registry, Clinical Epidemiology and Biostatistics, IRCCS-CROB, Basilicata, Rionero in Vulture, Italy.

(17)Mantova Cancer Registry, Epidemiology Unit, Agenzia di Tutela della Salute (ATS) della Val Padana, Mantova, Italy.

(18)Brindisi Cancer Registry, Local Health Authority, Brindisi, Italy.

(19)Cancer Registry of Brescia Province, Epidemiology Unit, Brescia Health Protection Agency, Brescia, Italy.

(20)Epidemiology Unit, Azienda Unità Sanitaria Locale – IRCCS di Reggio Emilia, Via Amendola 2, 42122 Reggio Emilia, Italy.

(21)Section of Public Health and RTUP Register, Department of Experimental Medicine, University of Perugia, Perugia, Italy.

(22)South-Tyrol Tumor Registry, Bolzano, Italy.

(23)Department of Health Promotion, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy.

(24)Lecce Province Cancer Registry, Lecce, Italy.

(25)Parma Cancer Registry, Medical Oncology Unit, University Hospital of Parma, Parma, Italy.

(26)Catania, Messina, and Enna Cancer Registry, Catania, Italy.

(27)Trento Province Cancer Registry, Unit of Clinical Epidemiology, Trento, Italy.

(28)Barletta, Andria, Trani Cancer Registry, BAT Province, Barletta, Italy.

(29)Epidemiology Unit, Cancer Registry of ATS Brianza, Health Protection Agency, Monza, Italy.

(30)Piedmont Cancer Registry, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy.

(31)Veneto Tumour Registry, Azienda Zero, University of Padova-DIMED, Padova, Italy.

(32)Bergamo Cancer Registry, ATS Bergamo, Bergamo, Italy.

(33)Catanzaro ASP Cancer Registry, Catanzaro, Italy.

(34)Trapani and Agrigento Cancer Registry, Trapani, Italy.

(35)Lombardy Cancer Registry-Varese Province, Cancer Registry Unit, Department of Research, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.

(36)Cancer Registry of the Province of Siracusa, Siracusa, Italy.

(37)Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.

(38)Macerata Province Cancer Registry, University of Camerino, Camerino, Italy.

(39)Romagna Cancer Registry, Romagna Cancer Institute, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Forlì, Italy; Cancer Prevention Unit, Local Health Authority, Forlì, Italy.

OBJECTIVE: The incidence of vulvar squamous cell carcinoma has increased for decades in most Western countries – a trend virtually restricted to women aged <50 or 60 years. In southern Europe, conversely, the trends have been insufficiently studied. This article reports a study from Italy.

METHOD: Thirty-eight local cancer registries, currently covering 15,274,070 women, equivalent to 49.2% of the Italian national female population, participated. Invasive cancers registered between 1990 and 2015 with an International Classification of Diseases for Oncology, 3rd revision, topography code C51 and morphology codes compatible with vulvar squamous cell carcinoma (n = 6294) were eligible. Incidence trends were analysed using joinpoint regression models, with calculation of the estimated annual percent change (EAPC), and age-period-cohort models.

RESULTS: Total incidence showed a regular and significant decreasing trend (EAPC, -0.96; 95% confidence interval (CI), -1.43 to -0.48). This was entirely accounted for by women aged ≥60 years (EAPC, -1.34; 95% CI, -1.86 to -0.81). For younger women, the EAPC between 1990 and 2012 was 1.20 (95% CI, 0.34 to 2.06) with a non-significant acceleration thereafter. This pattern did not vary substantially in a sensitivity analysis for the effect of geographic area and duration of the registry. The age-period-cohort analysis revealed a risk decrease in cohorts born between 1905 and 1940 and a new increase in cohorts born since 1945.

CONCLUSIONS: The decreasing trend observed among older women and the resulting decrease in total rate are at variance with reports from most Western countries. Age-period-cohort analysis confirmed a decreasing trend for earliest birth cohorts and an opposite one for recent ones.

DOI: 10.1016/j.ygyno.2020.03.013

PMID: 32273199

Conflict of interest statement: Declaration of competing interest The authors have no competing interest.

9. Infect Agent Cancer. 2020 Apr 1;15:20. doi: 10.1186/s13027-020-00286-8. eCollection 2020.

Role of human papillomavirus infection in the etiology of vulvar cancer in Italian women.

Preti M(1), Rotondo JC(2)(3), Holzinger D(4), Micheletti L(1), Gallio N(1), McKay-Chopin S(2), Carreira C(2), Privitera SS(5), Watanabe R(2), Ridder R(6)(7), Pawlita M(4), Benedetto C(1), Tommasino M(2), Gheit T(2).

Author information:

(1)1Department of Surgical Sciences, University of Turin, Turin, Italy.

(2)2International Agency for Research on Cancer, Lyon, France.

(3)3Department of Morphology, Surgery and Experimental Medicine; Section of Pathology, Oncology and Experimental Biology; Laboratories of Cell Biology and Molecular Genetics, University of Ferrara, Ferrara, Italy.

(4)4Infections and Cancer Epidemiology, Infections and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.

(5)5Department of Oncology, Città della Salute e della Scienza, University of Turin, Turin, Italy.

(6)Roche mtm laboratories, Mannheim, Germany.

(7)7Ventana Medical Systems Inc., Tucson, AZ USA.

BACKGROUND: Vulvar squamous cell carcinoma (VSCC) is a rare malignancy of the female genital tract. We aimed to determine the mucosal high-risk human papillomavirus (HPV)-attributable fraction of VSCCs from Italian women using multiple markers of viral infections.

METHODS: VSCCs and 8 metastatic lymph node samples from 107 Italian women were analyzed by a highly type-specific multiplex genotyping assay for the presence of DNA from 119 different HPVs. Tissues were further analyzed for HPV RNA and for upregulation of the cellular protein p16INK4a.

RESULTS: The rate of mucosal HPV-related tumors defined by viral DNA and RNA positivity was low (7.8%). HPV16 was the most prevalent, followed by 53, 56, and 58. Only five (4.9%) p16INK4a-positive tumors were also positive for both viral DNA and RNA. One (14.3%) metastatic lymph node sample was positive for all three markers. DNA of cutaneous HPVs was detected in only two VSCCs, i.e. genus beta types 5 and 110.

CONCLUSION: A small proportion of Italian VSCCs is putatively HPV-related, i.e. positive for both viral DNA and RNA of the same type, thus reinforcing the importance of HPV vaccination. Moreover, this study suggests that a direct role of HPV from genus beta and gamma in vulvar carcinogenesis is unlikely.

DOI: 10.1186/s13027-020-00286-8

PMCID: PMC7110671

PMID: 32266002

Conflict of interest statement: Competing interestsR. Ridder is an employee of Roche. All other authors report no conflict of interest.

10. J Low Genit Tract Dis. 2020 Jul;24(3):334-335. doi: 10.1097/LGT.0000000000000533.

International Society for the Study of Vulvovaginal Disease 2019 Presidential Address.

Preti M(1).

Author information:

(1)Department of Surgical Sciences University of Torino, Torino, Italy.

DOI: 10.1097/LGT.0000000000000533

PMID: 32205762

11. J Low Genit Tract Dis. 2020 Jul;24(3):332-333. doi: 10.1097/LGT.0000000000000513.

The International Classification of Diseases, 11th Revision: A Step-Back for Women With Vulvodynia?

Radici G(1), Preti M(1), Vieira-Baptista P(2)(3)(4), Stockdale CK(5), Bornstein J(6).

Author information:

(1)Department of Surgical Sciences, University of Torino, Torino, Italy.

(2)Hospital Lusíadas Porto, Porto, Portugal.

(3)LAP – Laboratório de Anatomia Patológica, Porto, Portugal.

(4)Lower Genital Tract Unit, Gynecology Department, Centro Hospitalar de São João, Porto, Portugal.

(5)Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA.

(6)Department of Obstetrics and Gynecology, Galilee Medical Center and Azrieli Faculty of Medicine, Bar Ilan University, Nahariya, Israel.

OBJECTIVE: The aim of the study was to compare the International Classification of Diseases, 11th revision, (ICD-11) with current terminology of vulvodynia, approved by a broad-based consensus of the International Society for the Study of Vulvovaginal Disease (ISSVD), the International Society for the Study of Women Sexual Health (ISSWSH), and the International Pelvic Pain Society (IPPS).

METHODS: The diagnostic criteria and descriptions of vulvodynia as well as the definition and classification of chronic pain in ICD-11 were reviewed and compared with the Consensus Terminology and Classification of Persistent Vulvar Pain and Vulvodynia, endorsed in 2015 by the ISSVD, ISSWSH, and IPPS.

RESULTS: Diagnostic criteria and descriptors of vulvodynia in the ICD-11 are outdated. Moreover, vulvodynia is not identified among chronic pain diagnoses, despite fulfilling the diagnostic criteria of chronic primary pain. Specifically, vulvodynia is a vulvar pain of at least 3-month duration, which is associated with significant emotional distress and functional disability, and is not better accounted for by another specific condition.

CONCLUSIONS: The ICD-11 is not aligned with current vulvodynia diagnostic criteria and terminology, approved by the ISSVD, ISSWSH, and IPPS. Collaboration among the International Association for the Study of Pain Task Force on Classification of Chronic Pain, ICD team, ISSVD, ISSWSH, and IPPS is needed to harmonize terminologies, codes, and clinical approach regarding vulvar pain and vulvodynia classification.

DOI: 10.1097/LGT.0000000000000513

PMID: 32068619

12. J Low Genit Tract Dis. 2020 Jan;24(1):62-68. doi: 10.1097/LGT.0000000000000501.

The International Society for the Study of Vulvovaginal Disease Surgical Oncological Procedure Definitions Committee “Surgical Terminology for Vulvar Cancer Treatment”.

Micheletti L(1), Haefner H(2), Zalewski K(3)(4), MacLean A(5), Gomez Cherey F(6), Pereira C(7), Sluga C(8), Solé-Sedeno JM(9), Vargas-Hernandez VM(10), Preti M(1).

Author information:

(1)Department of Obstetrics and Gynaecology, University of Torino, Torino, Italy.

(2)Department of Obstetrics and Gynecology, Michigan Medicine, Ann Arbor, MI.

(3)Department of Gynecologic Oncology, Holycross Cancer Center, Kielce, Poland.

(4)Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Institute – Oncology Center, Warsaw, Poland.

(5)Retired from University of London, London.

(6)Hospital de Clinicas “Jose de San Martin” Buenos Aires University, Buenos Aires, Argentina.

(7)Centro Materno Infantil do Norte, Centro Hospitalar Universitario do Porto, Oporto, Portugal.

(8)Department of Gynecology, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.

(9)Department of Obstetrics and Gynaecology, Universitat Autònoma de Barcelona, Hospital del Mar, Barcelona, Spain.

(10)Department of Gynecology, Clinica de Salud Femenina, Ciudad de Mexico, Mexico.

OBJECTIVES: The International Society for the Study of Vulvovaginal Disease (ISSVD) Surgical Oncological Procedure Definitions Committee propose a consistent terminology based on well-defined and reproducible anatomic landmarks that can be used by all who are involved in care of patients with vulvar conditions.

MATERIALS AND METHODS: The fundamental principles behind the new terminology contained descriptions of the area extension and depth of the surgical procedure.

RESULTS: Vulvar Surgical Topographic Anatomy LandmarksExtension. The internal border of the vulva is the hymenal ring. The genitocrural folds are the external lateral borders.The vertical line through the clitoris and the anus defines lateral portions of the vulva.The horizontal line from the upper border of the hymenal ring defines anterior and posterior portion of the vulva.Depth. The floor of the vulva is represented by the median perineal fascia or perineal membrane of the urogenital diaphragm.A. Vulvectomy1. Extension: partial/total vulvectomy. Removal of part/entire vulvar/perineal integument independent of the depth.2. Depth: superficial/deep. Removal of the most superficial layer/removal of the vulvar tissue to the superficial aponeurosis of the urogenital diaphragm and/or pubic periosteum.B. Inguinofemoral lymphadenectomy1. Superficial inguinofemoral lymphadenectomy. Removal of the nodes located beside the inguinal ligament and along the great saphenous vein.2. Deep femoral lymphadenectomy. Removal of the nodes below the cribriform lamina and medial to the femoral vein.

CONCLUSIONS: This terminology helps avoid confusion and promote better understanding and exchange of experiences among gynecologic oncologists involved in vulvar carcinoma care.

DOI: 10.1097/LGT.0000000000000501

PMID: 31860578 [Indexed for MEDLINE]

13. J Low Genit Tract Dis. 2020 Jan;24(1):61. doi: 10.1097/LGT.0000000000000503.

Upcoming Position Papers From the International Society for the Study of Vulvovaginal Disease.

Foster DC(1), Stockdale CK(2), Preti M(3).

Author information:

(1)Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, NY.

(2)Department Obstetrics & Gynecology, University of Iowa Healthcare, Iowa City, IA.

(3)Department of Surgical Sciences, University of Torino, Torino, Italy.

DOI: 10.1097/LGT.0000000000000503

PMID: 31860577

14. Neurourol Urodyn. 2020 Jan;39(1):473-476. doi: 10.1002/nau.24229. Epub 2019 Nov 25.

Response letter to comments related to “The clinical role of LASER for vulvar and vaginal treatments in gynecology and female urology: An ICS/ISSVD best practice consensus document”.

Digesu GA(1), Vieira-Baptista P(2)(3), Tailor V(1), Stockdale C(4), Preti M(5).

Author information:

(1)Department of Urogynaecology, Imperial College Healthcare, London, UK.

(2)Department of Obstetrics and Gynecology, Hospital Lusíadas Porto, Porto, Portugal.

(3)Lower Genital Tract Unit, Centro Hospitalar de São João, Porto, Portugal.

(4)Department of Obstetrics and Gynecology, University of Iowa, Iowa City, Iowa.

(5)Department of Obstetrics and Gynecology, University of Torino, Torino, Italy.

Comment in

Neurourol Urodyn. 2020 Mar;39(3):1026-1027.

Comment on

Neurourol Urodyn. 2019 Nov;38(8):2383-2384.

Neurourol Urodyn. 2019 Sep;38(7):2010-2011.

DOI: 10.1002/nau.24229

PMID: 31765486 [Indexed for MEDLINE]

15. Minerva Ginecol. 2019 Dec;71(6):442-459. doi: 10.23736/S0026-4784.19.04443-5. Epub 2019 Nov 13.

[HPV vaccination: not only female adolescents and not only prophylactic. Review and position paper of the Italian HPV Study Group (IHSG)].

[Article in Italian]

Origoni M(1), Cristoforoni P(2), Mariani L(3), Costa S(4), Preti M(5), Sandri MT(6), Preti EP(7), Ghelardi A(8), Perino A(9); Italian HPV Study Group (IHSG).

Author information:

(1)Dipartimento di Ginecologia e Ostetricia, Università Vita Salute San Raffaele, Milano, Italia – massimo.origoni@hsr.it.

(2)Clinica Villa Montallegro, Genova, Italia.

(3)Istituto Regina Elena, Roma, Italia.

(4)Centro Demetra ARTeBiOS, Lugo, Ravenna, Italia.

(5)Dipartimento di Ginecologia e Ostetricia, Università di Torino, Torino, Italia.

(6)Istituto Clinico Humanitas, Milano, Italia.

(7)Istituto Europeo di Oncologia (IEO), Milano, Italia.

(8)ASL Toscana Nord Ovest, Massa Carrara, Italia.

(9)Dipartimento di Ginecologia e Ostetricia, Università di Palermo, Palermo, Italia.

HPV vaccination has been introduced in clinical practice in recent years and represents the most effective strategy of primary prevention of cervical carcinoma and of female genital preneoplastic conditions. One of the major issues of the subject is represented by vaccination coverage of the target population. Since its introduction, HPV vaccine efficacy has been progressively demonstrated also towards extragenital HPV-correlated conditions and in males too. Moreover, even subjects of older age groups or subjects who already had HPV infections have been demonstrated to received benefits from vaccination, due to improvements of their immunological response. Recently, vaccine efficacy has also been investigated in terms of adjuvant administration after treatments of preneoplastic or benign conditions of the female lower genital tract caused by HPVs; preliminary results indicate an interesting and promising field of application. On this basis, in this article an analysis of the state of the art has been performed, with specific regard to the Italian scenario and with the focus of future perspectives of implementation of the HPV vaccination policy. From the available evidences, the Italian HPV Study Group recommends the extension of systematic HPV vaccination to males too, to adult subjects and also after conservative treatment of genital HPV correlated conditions.

DOI: 10.23736/S0026-4784.19.04443-5

PMID: 31741364 [Indexed for MEDLINE]

16. Eur J Contracept Reprod Health Care. 2019 Oct;24(5):337-346. doi: 10.1080/13625187.2019.1643835. Epub 2019 Jul 31.

Systematic review and meta-analysis of the effects of treatment modalities for vestibulodynia in women.

Pérez-López FR(1)(2), Bueno-Notivol J(3), Hernandez AV(4)(5), Vieira-Baptista P(6)(7), Preti M(8), Bornstein J(9).

Author information:

(1)Department of Obstetrics and Gynecology, University of Zaragoza Faculty of Medicine , Zaragoza , Spain.

(2)Red de Investigacion de Ginecologia, Obstetricia y Reproduccion, Instituto Aragonés de Investigaciones Sanitarias , Zaragoza , Spain.

(3)Department of Psychiatry, Hospital Miguel Servet , Zaragoza , Spain.

(4)Hartford Hospital Evidence-Based Practice Center, University of Connecticut , Hartford , CT , USA.

(5)Vicerrectorado de Investigación, Universidad San Ignacio de Loyola (USIL) , Lima , Peru.

(6)Department of Obstetrics and Gynecology, Hospital Lusíadas Porto , Porto , Portugal.

(7)Lower Genital Tract Unit, Centro Hospitalar de São João , Porto , Portugal.

(8)Department of Obstetrics and Gynecology, University of Torino , Torino , Italy.

(9)Department of Obstetrics and Gynecology, Galilee Medical Center, Nahariya and Azrieli Faculty of Medicine, Bar Ilan University , Safed , Israel.

Objective: To quantify the effects of available treatments of vestibulodynia. Methods: Systematic review of randomised controlled trials (RCTs) in six search engines until December 2018, comparing any intervention vs. placebo or sham in women with vestibulodynia. Primary outcome was dyspareunia assessed with visual analogue (VAS) or numeric rating (NRS) scales. Secondary outcomes were daily vestibular symptoms (DVS), McGill Pain Questionnaire (MPQ) and Index of Sexual Satisfaction (ISS). Effects were described as mean differences (MDs) with their 95% confidence intervals (CIs). Traditional and frequentist network meta-analyses (NMA) were performed using random effect models. Results: Four RCTs (n = 275) were included evaluating vaginal cream of conjugated oestrogens, oral desipramine with or without topical lidocaine, topical lidocaine, laser therapy and transcranial direct current. In traditional MA, interventions did not reduce dyspareunia (MD = 0.08; 95%CI = -0.49 to 0.64), DVS (MD = -0.04; 95%CI = -0.31 to 0.24; 4 interventions), or MPQ (MD = -0.17; 95%CI = -2.16 to 1.81; 4 interventions). ISS was significantly improved (MD = -5.14; 95%CI = -9.52 to -0.75). In NMA, oral desipramine with or without lidocaine significantly improved ISS vs. other treatments. Conclusions: Several existing interventions were not associated with improvements in vestibulodynia. There only was improvement of sexual function with oral desipramine with or without lidocaine.

DOI: 10.1080/13625187.2019.1643835

PMID: 31364893 [Indexed for MEDLINE]

17. Pain. 2019 Jul;160(7):1680-1681. doi: 10.1097/j.pain.0000000000001559.

Vulvodynia: a neglected chronic pain diagnosis.

Bornstein J(1), Preti M(2), Radici G(2), Stockdale CK(3), Vieira-Baptista P(4).

Author information:

(1)Department of Obstetrics and Gynecology, Galilee Medical Center and Azrieli Faculty of Medicine, Bar Ilan University, Nahariya, Israel.

(2)Department of Obstetrics and Gynecology, University of Torino, Torino, Italy.

(3)Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA.

(4)Hospital Lusíadas Porto and Unidade de Tracto Genital Inferior, Serviço de Ginecologia e Obstetrícia, Centro Hospitalar de São João, Porto, Portugal.

Comment in

Pain. 2019 Jul;160(7):1681-1683.

Comment on

Pain. 2019 Jan;160(1):19-27.

DOI: 10.1097/j.pain.0000000000001559

PMID: 31219952 [Indexed for MEDLINE]

18. J Low Genit Tract Dis. 2019 Apr;23(2):151-160. doi: 10.1097/LGT.0000000000000462.

The Clinical Role of LASER for Vulvar and Vaginal Treatments in Gynecology and Female Urology: An ICS/ISSVD Best Practice Consensus Document.

Preti M(1), Vieira-Baptista P(2)(3), Digesu GA(4), Bretschneider CE(5), Damaser M(5)(6)(7), Demirkesen O(8), Heller DS(9), Mangir N(10)(11), Marchitelli C(12), Mourad S(13), Moyal-Barracco M(14), Peremateu S(12), Tailor V(4), Tarcan T(15), De EJB(16), Stockdale CK(17).

Author information:

(1)Department of Obstetrics and Gynecology, University of Torino, Torino, Italy.

(2)Hospital Lusíadas Porto.

(3)Lower Genital Tract Unit, Centro Hospitalar de São João, Porto, Portugal.

(4)Imperial College Healthcare, Department of Urogynaecology, London, UK.

(5)Center for Urogynecology and Pelvic Reconstructive Surgery, Obstetrics, Gynecology and Women’s Health Institute, Cleveland Clinic.

(6)Glickman Urological and Kidney Institute and Department of Biomedical Engineering Lerner Research Institute, Cleveland Clinic.

(7)Advanced Platform Technology Center Louis Stokes Cleveland VA Medical Center, Cleveland, OH.

(8)Istanbul University Cerrahpaşa Faculty of Medicine, Department of Urology, Istanbul, Turkey.

(9)Department of Pathology & Laboratory Medicine, Rutgers-New Jersey Medical School, Newark, NJ.

(10)Kroto Research Institute, Department of Material Science and Engineering, University of Sheffield.

(11)Royal Hallamshire Hospital, Department of Urology, Sheffield, UK.

(12)Department of Gynecology, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.

(13)Ain Shams University, Department of Urology, Cairo, Egypt.

(14)Department of Dermatology, Hôpital Tarnier-Cochin, Paris, France.

(15)Marmara University School of Medicine, Department of Urology, Istanbul, Turkey.

(16)Department of Urology, Massachusetts General Hospital-Harvard Medical School Boston, MA.

(17)Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA.

Comment in

J Urol. 2019 Nov;202(5):871-872.

In this best practice document, we propose recommendations for the use of LASER for gynecologic and urologic conditions such as vulvovaginal atrophy, urinary incontinence, vulvodynia, and lichen sclerosus based on a thorough literature review. Most of the available studies are limited by their design; for example, they lack a control group, patients are not randomized, follow-up is short term, series are small, LASER is not compared with standard treatments, and most studies are industry sponsored. Because of these limitations, the level of evidence for the use of LASER in the treatment of these conditions remains low and does not allow for definitive recommendations for its use in routine clinical practice. Histological evidence is commonly reported as proof of tissue regeneration after LASER treatment. However, the histological changes noted can also be consistent with reparative changes after a thermal injury rather than necessarily representing regeneration or restoration of function. The use of LASER in women with vulvodynia or lichen sclerosus should not be recommended in routine clinical practice. There is no biological plausibility or safety data on its use on this population of women. The available clinical studies do not present convincing data regarding the efficacy of LASER for the treatment of vaginal atrophy or urinary incontinence. Also, although short-term complications seem to be uncommon, data concerning long-term outcomes are lacking. Therefore, at this point, LASER is not recommended for routine treatment of the aforementioned conditions unless part of well-designed clinical trials or with special arrangements for clinical governance, consent, and audit.

DOI: 10.1097/LGT.0000000000000462

PMCID: PMC6462818

PMID: 30789385 [Indexed for MEDLINE]

Conflict of interest statement: No conflicts of interest to declare

19. J Low Genit Tract Dis. 2019 Apr;23(2):161-163. doi: 10.1097/LGT.0000000000000461.

Descriptors of Vulvodynia: A Multisocietal Definition Consensus (International Society for the Study of Vulvovaginal Disease, the International Society for the Study of Women Sexual Health, and the International Pelvic Pain Society).

Bornstein J(1), Preti M(2), Simon JA(3), As-Sanie S(4), Stockdale CK(5), Stein A(6), Parish SJ(7), Radici G(2), Vieira-Baptista P(8), Pukall C(9), Moyal-Barracco M(10), Goldstein A(11); International Society for the Study of Vulvovaginal Disease (ISSVD), the International Society for the Study of Womenʼs Sexual Health (ISSWSH), and the International Pelvic Pain Society (IPPS).

Author information:

(1)Department of Obstetrics and Gynecology, Galilee Medical Center and Azrieli Faculty of Medicine, Bar Ilan University, Nahariya, Israel.

(2)Department of Obstetrics and Gynecology, University of Torino, Torino, Italy.

(3)IntimMedicine Specialists and Department of Obstetrics and Gynecology, George Washington University, Washington, DC.

(4)Consultative Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI.

(5)Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA.

(6)Beyond Basics Physical Therapy Midtown, New York, NY.

(7)Departments of Clinical Psychiatry and Medicine, Weill Cornell Medical College, New York Presbyterian Hospital/Westchester Division, New York, NY.

(8)Hospital Lusíadas Porto and Unidade de Tracto Genital Inferior, Serviço de Ginecologia e Obstetrícia, Centro Hospitalar de São João, Porto, Portugal.

(9)Department of Psychology, Queen’s University, Kingston, Ontario, Canada.

(10)Tarnier-Cochin Hospital, Department of Dermatology, Paris, France.

(11)Department of Obstetrics and Gynecology, The George Washington University School of Medicine and Health Sciences and the Center for Vulvovaginal Disorders, Washington, DC.

OBJECTIVES: Three scientific societies, the International Society for the Study of Vulvovaginal Disease (ISSVD), the International Society for the Study of Women Sexual Health (ISSWSH), and the International Pelvic Pain Society (IPPS) developed the “2015 ISSVD, ISSWSH, and IPPS Consensus Terminology and Classification of Persistent Vulvar Pain and Vulvodynia” (referred to as the “2015 consensus terminology”).The terminology included 11 descriptors of vulvodynia. However, the definitions of the descriptors were not included in the 2015 consensus terminology publications. The objective of this article was to provide these definitions.

MATERIALS AND METHODS: The ISSVD led a discussion on the definitions for the 11 vulvodynia descriptors, with participation from the ISSWSH and IPPS. The definitions were created through a consensus process.

RESULTS: The definitions are described and the rationale for their choice is elucidated.

CONCLUSIONS: The definitions of vulvodynia descriptors were determined by a multistaged process of discussion among health care providers with expertise in the pathophysiology, evaluation, and treatment of vulvodynia. The definitions were approved by the ISSVD, ISSWSH, and IPPS. It is recommended that these definitions of vulvodynia descriptors as well as the 2015 consensus terminology be used for the classification of vulvodynia.

DOI: 10.1097/LGT.0000000000000461

PMID: 30768446 [Indexed for MEDLINE]

20. Neurourol Urodyn. 2019 Mar;38(3):1009-1023. doi: 10.1002/nau.23931. Epub 2019 Feb 11.

The clinical role of LASER for vulvar and vaginal treatments in gynecology and female urology: An ICS/ISSVD best practice consensus document.

Author information:

(1)Department of Obstetrics and Gynecology, University of Torino, Torino, Italy.

(2)Hospital Lusíadas Porto, Porto, Portugal.

(3)Lower Genital Tract Unit, Centro Hospitalar de São João, Porto, Portugal.

(4)Department of Urogynaecology, Imperial College Healthcare, London, UK.

(5)Center for Urogynecology and Pelvic Reconstructive Surgery, Obstetrics, Gynecology and Women’s Health Institute, Cleveland Clinic, Cleveland, Ohio.

(6)Glickman Urological and Kidney Institute and Department of Biomedical Engineering Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.

(7)Advanced Platform Technology Center, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio.

(8)Faculty of Medicine, Department of Urology, Istanbul University Cerrahpaşa, Istanbul, Turkey.

(9)Department of Pathology and Laboratory Medicine, Rutgers-New Jersey Medical School, Newark, New Jersey.

(10)Kroto Research Institute, Department of Material Science and Engineering, University of Sheffield, Sheffield, UK.

(11)Department of Urology, Royal Hallamshire Hospital, Sheffield, UK.

(12)Department of Gynecology, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.

(13)Department of Urology, Massachusetts General Hospital-Harvard Medical School Boston, Boston, Massachusetts.

(14)Department of Dermatology, Hôpital Tarnier-Cochin, Paris, France.

(15)Department of Urology, Ain Shams University, Cairo, Egypt.

(16)Department of Urology, Marmara University School of Medicine, Istanbul, Turkey.

(17)Department of Obstetrics and Gynecology, University of Iowa, Iowa City, Iowa.

Erratum in

Neurourol Urodyn. 2020 Mar;39(3):1028.

Comment in

Neurourol Urodyn. 2019 Nov;38(8):2383-2384.

Neurourol Urodyn. 2019 Sep;38(7):2010-2011.

Int Braz J Urol. 2020 May-Jun;46(3):469-470.

BACKGROUND: The clinical role of LASER for vulvar and vaginal treatments in gynecology and female urology is controversial.

AIMS: In this best practice document, we propose recommendations for the use of LASER for gynecologic and urologic conditions such as vulvovaginal atrophy, urinary incontinence, vulvodynia, and lichen sclerosus based on a thorough literature review.

MATERIALS & METHODS: This project was developed between January and September 2018. The development of this document followed the ICS White Paper Standard Operating Procedures.

RESULTS: Most of the available studies are limited by their design; for example they lack a control group, patients are not randomized, follow up is short term, series are small, LASER is not compared with standard treatments, and studies are industry sponsored. Due to these limitations, the level of evidence for the use of LASER in the treatment of these conditions remains low and does not allow for definitive recommendations for its use in routine clinical practice. Histological evidence is commonly reported as proof of tissue regeneration following LASER treatment. However, the histological changes noted can also be consistent with reparative changes after a thermal injury rather than necessarily representing regeneration or restoration of function. The use of LASER in women with vulvodynia or lichen sclerosus should not be recommended in routine clinical practice. There is no biological plausibility or safety data on its use on this population of women.

DISCUSSION: The available clinical studies do not present convincing data regarding the efficacy of LASER for the treatment of vaginal atrophy or urinary incontinence. Also, while short-term complications seem to be uncommon, data concerning long-term outcomes are lacking.

CONCLUSION: At this point, LASER is not recommended for routine treatment of the aforementioned conditions unless part of well-designed clinical trials or with special arrangements for clinical governance, consent, and audit.

DOI: 10.1002/nau.23931

PMID: 30742321 [Indexed for MEDLINE]

21. Neurourol Urodyn. 2019 Mar;38(3):1005-1008. doi: 10.1002/nau.23927. Epub 2019 Jan 29.

The energy based devices for vaginal “rejuvenation,” urinary incontinence, vaginal cosmetic procedures, and other vulvo-vaginal disorders: An international multidisciplinary expert panel opinion.

Digesu GA(1), Tailor V(1), Preti M(2), Vieira-Baptista P(3)(4), Tarcan T(5), Stockdale C(6), Mourad S(7).

Author information:

(1)Imperial College Healthcare, Department of Urogynaecology, London, UK.

(2)Department of Obstetrics and Gynecology, University of Torino, Torino, Italy.

(3)Hospital Lusíadas Porto, Porto, Portugal.

(4)Lower Genital Tract Unit, Centro Hospitalar de São João, Porto, Portugal.

(5)Marmara University School of Medicine, Department of Urology, Istanbul, Turkey.

(6)Department of Obstetrics and Gynecology, University of Iowa, Iowa City, Iowa.

(7)Ain Shams University, Department of Urology, Cairo, Egypt.

AIMS: Energy-based devices using radiofrequency and laser technologies have gained popularity as therapies for vaginal atrophy, urinary incontinence, and vaginal prolapse. They have been promoted by cosmetic and aesthetic industries for vaginal “laxity” and vaginal “rejuvenation,” both of which are undefined conditions and terms. This article aims to review the current available literature and its quality on this emerging technology.

METHODS: An international panel of gynaecologists, urogynaecologists, and urologists undertook a review of the available published literature, identifying articles, guidance, and society statements on the use vaginal energy-based devices.

RESULTS: There is currently no formal guidance for the use of vaginal energy based therapies. No randomized controlled trials have been published. No comparative studies to existing treatment has been carried out. Studies suggest that vaginal laser can be used in the treatment of vaginal prolapse or “vaginal laxity” and stress urinary incontinence with no quality evidence supporting the use of the therapy for vaginal atrophy or lichen sclerosis.

CONCLUSIONS: This international group propose that whilst there remains a paucity of good quality data describing the safety, benefits, and appropriate use of vaginal radiofrequency or laser treatments in gynaecology and urogynaecology, a consensus best practice document by an established scientific community needs to be developed.

DOI: 10.1002/nau.23927

PMID: 30697814 [Indexed for MEDLINE]

22. J Low Genit Tract Dis. 2019 Jan;23(1):39-42. doi: 10.1097/LGT.0000000000000441.

Onclarity Human Papillomavirus Extended Genotyping in the Management of Cervical Intraepithelial Neoplasia 2+ Lesions.

Bottari F(1), Iacobone AD(2), Boveri S(3), Preti EP(2), Franchi D(2), Mariani L(4), Preti M(5), Landoni F(6), Passerini R(1), Sandri MT(7).

Author information:

(1)Division of Laboratory Medicine, European Institute of Oncology IRCCS, Milan, Italy.

(2)Preventive Gynecology Unit, European Institute of Oncology IRCCS, Milan, Italy.

(3)Scientific Directorate, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.

(4)HPV-Unit, Regina Elena National Cancer Institute, Rome, Italy.

(5)Department of Obstetrics and Gynecology, University of Torino, Turin, Italy.

(6)Gynecologic Oncology Unit, Department of Obstetrics and Gynecology, ASST-Monza, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.

(7)Clinical Analysis Laboratory, Humanitas Research Hospital, Rozzano, Milan, Italy.

OBJECTIVE: Many methods are available today for human papillomavirus (HPV) testing; they differ for technology, targets, and information on the genotypes detected. In this study, we evaluated the performance of the Onclarity HPV assay in detection and follow-up of cervical preneoplastic lesions.

MATERIALS AND METHODS: One hundred sixty-seven women referred to the European Institute of Oncology, Milan, for treatment of cervical lesions were enrolled. We investigated the utility of Onclarity extended genotyping HPV test in the management of cervical intraepithelial neoplasia (CIN) 2+ preneoplastic lesion.

RESULTS: At baseline, the concordance was 92% (150/163) between Onclarity and Hybrid Capture 2 (HC2) and 93% (142/152) between Onclarity and linear array, respectively. At follow-up, the concordance between Onclarity and HC2 was 80%. Seven women relapsed: 6 had persistence of the same genotypes and 1 patient tested negative not only with Onclarity but also with HC2 for the presence of a low-risk genotype in the sample.

CONCLUSIONS: This study showed that the evaluation of the HPV genotype persistence may represent a valid option to monitor patients treated for CIN 2+ lesions, because relapses were detected only in patients with persistence of the same genotype detected at baseline.

DOI: 10.1097/LGT.0000000000000441

PMID: 30371554 [Indexed for MEDLINE]

23. Case Rep Womens Health. 2018 Sep 12;20:e00079. doi: 10.1016/j.crwh.2018.e00079. eCollection 2018 Oct.

Vulvodynia: A disease commonly hidden in plain sight.

Vieira-Baptista P(1)(2), Lima-Silva J(2), Pérez-López FR(3), Preti M(4), Bornstein J(5).

Author information:

(1)Hospital Lusíadas Porto, Portugal.

(2)Unidade de Tracto Genital Inferior, Serviço de Ginecologia e Obstetrícia, Centro Hospitalar de São João, Porto, Portugal.

(3)Department of Obstetrics and Gynecology, University of Zaragoza, Faculty of Medicine, Lozano-Blesa University Hospital, Zaragoza, Spain.

(4)Department of Obstetrics and Gynecology, University of Torino, Torino, Italy.

(5)Department of Obstetrics and Gynecology, Galilee Medical Center, Nahariya and Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel.

•Vulvodynia affects at least 6% of women, and can be found at any age and in all ethnic groups.•The diagnosis is one of exclusion but is very often missed.•Women with vulvodynia are frequently misdiagnosed as having vaginismus.•Failure to make the diagnosis often leads to irrelevant or deleterious examinations and treatments.

DOI: 10.1016/j.crwh.2018.e00079

PMCID: PMC6142188

PMID: 30245974

24. J Gynecol Oncol. 2018 Sep;29(5):e61. doi: 10.3802/jgo.2018.29.e61. Epub 2018 Apr 13.

Prognostic impact of reduced tumor-free margin distance on long-term survival in FIGO stage IB/II vulvar squamous cell carcinoma.

Micheletti L(1), Preti M(2), Cintolesi V(2), Corvetto E(3), Privitera S(4), Palmese E(2), Benedetto C(2).

Author information:

(1)Department of Obstetrics and Gynecology, Sant’Anna Hospital, University of Torino, Turin, Italy. michelettileonardo@gmail.com.

(2)Department of Obstetrics and Gynecology, Sant’Anna Hospital, University of Torino, Turin, Italy.

(3)Department of Surgical Sciences, Institute of Obstetrics and Gynecology, University of Cagliari, Cagliari, Italy.

(4)Department of Pathology and Cytology of Female Cancer, Childhood Cancer, and Rare Cancers, AOU Città della Salute e della Scienza, Turin, Italy.

OBJECTIVE: We aimed to identify the minimum tumor-free margin distance conferring long-term oncological safety in patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IB/II vulvar squamous cell carcinoma (VSCC).

METHODS: This was a retrospective cohort study in patients with stage IB/II VSCC treated at a single institution in Turin, Italy. The main aim was to identify the minimum tumor-free margin distance that confers oncological safety in early-stage VSCC. Patients were divided in groups according to tumor-free histological margin distance to compare survival outcomes. Overall survival (OS), disease-specific survival (DSS), and recurrence rate (RR) were estimated by the Kaplan-Meier method for the newly proposed and the currently recommended 8 mm margin cut-off. Log-rank test was used to compare survival between groups.

RESULTS: One hundred and fourteen patients met the study criteria. Median age was 68 years and median follow-up was 80 months. The minimum margin distance that conferred long-term oncological safety was 5 mm. OS, DSS were significantly lower in the <5 mm group when compared with the ≥5 mm group (p=0.002 and p=0.033, respectively) although no difference in RR was observed between groups. Analysis at the 8-mm cut-off indicated there is no difference in OS, DSS, or RR between groups.

CONCLUSION: FIGO stage IB/II VSCC patients’ prognosis is affected by margin distance. Long-term survival is significantly reduced in patients with tumor-free margins <5 mm, even in the absence of lymph node metastasis. Thus, these patients should be offered further surgical or adjuvant treatment.

DOI: 10.3802/jgo.2018.29.e61

PMCID: PMC6078886

PMID: 30022627 [Indexed for MEDLINE]

Conflict of interest statement: No potential conflict of interest relevant to this article was reported.

25. Menopause. 2018 Oct;25(10):1166-1167. doi: 10.1097/GME.0000000000001165.

To the Editor.

Vieira-Baptista P(1), Damaser M, Digesu A, Marchitelli C, Preti M, Stockdale C.

Author information:

(1)Unidade de Tracto Genital Inferior, Serviço de Ginecologia e Obstetrícia, Centro Hospitalar de São João and Hospital Lusíadas Porto, Portugal Glickman Urological and Kidney Institute and Department of Biomedical Engineering Lerner Research Institute Cleveland Clinic Cleveland, OH Advanced Platform Technology Center Louis Stokes Cleveland VA Medical Center Cleveland, OH Department of Urogynaecology, St. Mary’s Hospital, Imperial College Healthcare NHS Trust, London, England Department of Vulvar Diseases and Vulvovaginal Infections, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina Department of Obstetrics and Gynecology, University of Torino, Torino, Italy Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA.

Comment in

Menopause. 2018 Oct;25(10):1167-1168.

Comment on

Menopause. 2018 May;25(5):571-573.

DOI: 10.1097/GME.0000000000001165

PMID: 29975288 [Indexed for MEDLINE]

26. J Low Genit Tract Dis. 2018 Jul;22(3):264-265. doi: 10.1097/LGT.0000000000000398.

Vulvar Lichen Planus: A Risk Factor for Vulvar High-Grade Squamous Intraepithelial Lesion Recurrence?

Preti M(1), Micheletti L, Privitera S, Radici G, Gallio N, Benedetto C, Bucchi L.

Author information:

(1)Department of Obstetrics and Gynecology, University of Torino, Torino, Italy mario.preti@unito.it; Department of Obstetrics and Gynecology, University of Torino, Torino, Italy; Department of Pathology, and Cytology of Female Cancer, Childhood Cancer and Rare Cancers, AOU Città della Salute e della Scienza, Torino, Italy Department of Obstetrics and Gynecology, University of Torino, Torino, Italy Romagna Cancer Registry,Romagna Cancer Institute, Meldola, Forlì, Italy.

DOI: 10.1097/LGT.0000000000000398

PMID: 29933292 [Indexed for MEDLINE]

27. J Gynecol Oncol. 2017 Jul;28(4):e27. doi: 10.3802/jgo.2017.28.e27.

Risk factors for unrecognized invasive carcinoma in patients with vulvar high-grade squamous intraepithelial lesion at vulvoscopy-directed biopsy.

Preti M(1), Bucchi L(2), Ghiringhello B(3), Privitera S(3), Frau V(4), Corvetto E(4), Benedetto C(4), Micheletti L(4).

Author information:

(1)Department of Obstetrics and Gynecology, University of Torino, Torino, Italy. mpreti@cittadellasalute.to.it.

(2)Romagna Cancer Registry, Romagna Cancer Institute (IRST) IRCCS, Meldola, Forlì, Italy.

(3)Department of Pathology and Cytology of Female Cancer, Childhood Cancer, and Rare Cancers, AOU Città della Salute e della Scienza, Torino, Italy.

(4)Department of Obstetrics and Gynecology, University of Torino, Torino, Italy.

OBJECTIVE: To evaluate the prevalence and risk factors for unrecognized invasive carcinoma in a series of patients undergoing surgical excision after an office biopsy of vulvar high-grade squamous intraepithelial lesion (VHSIL).

METHODS: Two hundred and sixteen consecutive patients treated in a tertiary-level referral center for vulvar disease in north-western Italy were recruited. Patients’ records were reviewed by trained personnel. Factors showing a statistically significant (p<0.05) association with detection of stromal invasion at excisional surgery in univariate analysis were further examined in a backward stepwise multiple logistic regression model.

RESULTS: The median patient age was 50 years (range, 19-88). More than 25% patients with VHSIL at biopsy had associated cervical/vaginal intraepithelial neoplasia, and more than 35% had a multifocal lesion. Invasive carcinoma was detected in surgical specimens from 24 patients (11%). The depth of stromal invasion varied between 0.1 mm and 3.0 mm with a median of 0.5 mm. In multivariate analysis, the risk of invasive carcinoma detection was greater for patients in the highest tertile of age (p=0.008), for patients with a lesion ≥20 mm in size (p=0.013) and with clitoral involvement (p<0.001), and for patients presenting with a nodular lesion (p=0.078).

CONCLUSION: Our study suggests that patient age, lesion size, clitoral involvement and nodular appearance in patients with VHSIL at vulvoscopy-directed biopsy are independently associated with the risk of unrecognized invasive carcinoma.

DOI: 10.3802/jgo.2017.28.e27

PMCID: PMC5447137

PMID: 28541626 [Indexed for MEDLINE]

Conflict of interest statement: No potential conflict of interest relevant to this article was reported.

28. Int J Gynaecol Obstet. 2017 Mar;136(3):258-265. doi: 10.1002/ijgo.12075. Epub 2017 Jan 14.

Overview of the benefits and potential issues of the nonavalent HPV vaccine.

Mariani L(1), Preti M(2), Cristoforoni P(3), Stigliano CM(4), Perino A(5).

Author information:

(1)Regina Elena National Cancer Institute, HPV-Unit, Gynecologic Oncology, Rome, Italy.

(2)Department of Obstetrics and Gynecology, University of Torino, Turin, Italy.

(3)Villa Montallegro, Genoa, Italy.

(4)Unità Ospedaliera Complessa Ginecologia Preventiva, Azienda Sanitaria Provinciale di Cosenza, Castrovillari, Italy.

(5)Obstetrics and Gynecology, Ospedali Riuniti Villa Sofia Cervello, University of Palermo, Palermo, Italy.

HPV-related diseases affect anogenital and oropharyngeal regions, heavily affecting the psychosexual dimension of both male and female individuals. HPV vaccination programs based on a bivalent or quadrivalent vaccine have opened broad perspectives for primary prevention. A nonavalent HPV vaccine (9vHPV), covering nine genotypes (HPV6, HPV11, HPV16, HPV18, HPV31, HPV33, HPV45, HPV52, and HPV58), might provide further improvement in terms of direct protection. In the present report, efficacy and safety data from 9vHPV vaccine development programs are examined. Efficacy data come from a pivotal trial, which was conducted among women aged 16-26 years randomly assigned to receive either the 9vHPV or the quadrivalent HPV (4vHPV) vaccine. The 9vHPV vaccine was shown to have potential benefits as compared with 4vHPV, increasing the overall estimated rate of prevention to 90% for cervical cancer and up to 80% for precancerous cervical lesions. For all other HPV-related pre-invasive and invasive lesions, 9vHPV showed potentially greater disease reduction, depending on the anatomic region examined. Thus, the 9vHPV vaccine shows clinical potential for the prevention of HPV-related diseases in both sexes. Future adoption of 9vHPV will depend on factors including market price, cost-effectiveness data, use of a two-dose schedule, and safety and efficacy monitoring in real-life programs.

DOI: 10.1002/ijgo.12075

PMID: 28087890 [Indexed for MEDLINE]

29. Minerva Ginecol. 2016 Oct;68(5):620-1.

Nonavalent HPV vaccine (HPV-9): analysis of pre-registration data.

Mariani L(1), Cristoforoni P, Perino A, Stigliano CM, Preti M.

Author information:

(1)HPV Unit, Department of Gynecologic Oncology, Regina Elena National Cancer Institute, Rome, Italy – luciorm@libero.it.

PMID: 27430201 [Indexed for MEDLINE]

30. Obstet Gynecol. 2016 Feb;127(2):264-8. doi: 10.1097/AOG.0000000000001285.

The 2015 International Society for the Study of Vulvovaginal Disease (ISSVD) Terminology of Vulvar Squamous Intraepithelial Lesions.

Bornstein J(1), Bogliatto F, Haefner HK, Stockdale CK, Preti M, Bohl TG, Reutter J; ISSVD Terminology Committee.

Collaborators: Bornstein J, Bogliatto F, Bohl TG, Coady D, Haefner HK, Preti M, Reutter J, Selva-Nayagam P, Stockdale CK, Van-Beurden M.

Author information:

(1)Departments of Obstetrics and Gynecology, Galilee Medical Center and Bar-Ilan University Faculty of Medicine, Nahariya, Israel, Chivasso Civic Hospital, Chivasso, and University of Turin, Turin, Italy, University of Michigan Health System, Ann Arbor, Michigan, and University of Iowa, Iowa City, Iowa; Jean Hailes Medical Center for Women, Monash, Australia; and Piedmont Pathology Associates, Hickory, North Carolina.

OBJECTIVES: The impact of terminology for vulvar intraepithelial lesions has been significant over the years, because it has affected diagnosis, treatment, and research. The introduction of the Lower Anogenital Squamous Terminology (LAST) in 2012 raised 2 concerns in relation to vulvar lesions: firstly, the absence of reference to “differentiated vulvar intraepithelial neoplasia” (differentiated VIN) could lead to its being overlooked by health care providers, despite its malignant potential. Secondly, including the term “low-grade squamous intraepithelial lesion” (LSIL) in LAST recreated the potential for overdiagnosis and overtreatment for benign, self-limiting lesions.

MATERIALS AND METHODS: The International Society for the Study of Vulvovaginal Disease (ISSVD) assigned the terminology committee the task of developing a terminology to take these issues into consideration. The committee reviewed the development of terminology for vulvar SILs with the previous 2 concerns in mind and reviewed several new terminology options.

RESULTS: The final version accepted by the ISSVD contains the following: 1) Low-grade SIL of the vulva or vulvar LSIL, encompassing flat condyloma or human papillomavirus effect. 2) High-grade SIL or vulvar HSIL (which was termed “vulvar intraepithelial neoplasia usual type” in the 2004 ISSVD terminology). 3) Vulvar intraepithelial neoplasia, differentiated type.

CONCLUSION: The advantage of the new terminology is that it includes all types of vulvar SILs, it provides a solution to the concerns in relation to the application of LAST to vulvar lesion, and it is in accordance with the World Health Organization classification as well as the LAST, creating unity among clinicians and pathologists.

DOI: 10.1097/AOG.0000000000001285

PMID: 26942352 [Indexed for MEDLINE]

31. J Low Genit Tract Dis. 2016 Apr;20(2):180-3. doi: 10.1097/LGT.0000000000000186.

Vulvar Lichen Sclerosus and Neoplastic Transformation: A Retrospective Study of 976 Cases.

Micheletti L(1), Preti M, Radici G, Boveri S, Di Pumpo O, Privitera SS, Ghiringhello B, Benedetto C.

Author information:

(1)1Department of Gynecology and Obstetrics, University of Torino, Torino; 2Preventive Gynecology Unit, European Institute of Oncology, Milan; and 3Pathology Unit, S. Anna Hospital of Torino, Torino, Italy.

OBJECTIVE: The aim of the study was to estimate the neoplastic potential of vulvar lichen sclerosus (VLS).

MATERIALS AND METHODS: This was a retrospective study of 976 women with VLS. We recorded age at diagnosis of VLS, length of follow-up, and type of neoplasia, categorized as the following: (1) vulvar intraepithelial neoplasia (VIN), further subdivided in differentiated VIN (dVIN) and high-grade squamous intraepithelial lesion; (2) superficially invasive squamous cell carcinoma; and (3) frankly invasive squamous cell carcinoma. Neoplasia incidence risk, neoplasia incidence rate, and cumulative probability of progression to neoplasia according to the Kaplan-Meier method were estimated. Log-rank test was used to compare the progression-free survival curves by age at diagnosis of VLS.

RESULTS: The mean age at diagnosis of VLS was 60 (median = 60; range = 8-91) years. The mean length of follow-up was 52 (median = 21; range = 1-331) months. The following 34 patients developed a neoplasia: 8 VIN (4 dVIN, 4 high-grade squamous intraepithelial lesions), 6 keratinizing superficially invasive squamous cell carcinoma (5 with adjacent dVIN), and 20 keratinizing invasive squamous cell carcinoma (1 with adjacent dVIN). The neoplasia incidence risk was 3.5%. The neoplasia incidence rate was 8.1 per 1,000 person-years. The cumulative probability of progression to neoplasia increased from 1.2% at 24 months to 36.8% at 300 months. The median progression-free survival was significantly shorter in older women (≥70 years) when compared with that in younger women (p = .003).

CONCLUSIONS: Vulvar lichen sclerosus has a nonnegligible risk of neoplastic transformation and requires a careful and lifelong follow-up in all patients, particularly in elderly women. Early clinical and histological detection of preinvasive lesions is essential to reduce the risk of vulvar cancer.

DOI: 10.1097/LGT.0000000000000186

PMID: 26882123 [Indexed for MEDLINE]

32. J Cancer. 2016 Jan 1;7(1):107-14. doi: 10.7150/jca.13503. eCollection 2016.

HPV-Testing in Follow-up of Patients Treated for CIN2+ Lesions.

Mariani L(1), Sandri MT(2), Preti M(3), Origoni M(4), Costa S(5), Cristoforoni P(6), Bottari F(2), Sideri M(1).

Author information:

(1)1. HPV-UNIT, Regina Elena National Cancer Institute of Rome, Italy.

(2)2. Division of Laboratory Medicine, European Institute of Oncology, Milan, Italy.

(3)3. Department of Obstetrics and Gynecology – University of Turin, Italy.

(4)4. Obstetrics and Gynecology Unit, Vita-Salute San Raffaele University and IRCCS San Raffaele Hospital, Milan, Italy.

(5)5. MF Toniolo Hospital, Bologna, Italy.

(6)6. Villa Montallegro, Genoa, Italy.

Persistent positivity of HPV-DNA testing is considered a prognostic index of recurrent disease in patients treated for CIN2+. HPV detection, and particularly genotyping, has an adequate high rate of sensitivity and specificity (along with an optimal reproducibility), for accurately predicting treatment failure, allowing for an intensified monitoring activity. Conversely, women with a negative HPV-test 6 months after therapy have a very low risk for residual/recurrent disease, which leads to a more individualized follow-up schedule, allowing for a gradual return to the normal screening scheme. HPV testing should be routinely included (with or without cytology) in post-treatment follow-up of CIN2+ patients for early detection of recurrence and cancer progression. HPV genotyping methods, as a biological indicator of persistent disease, could be more suitable for a predictive role and risk stratification (particularly in the case of HPV 16/18 persistence) than pooled HPV-based testing. However, it is necessary to be aware of the performance of the system, adhering to strict standardization of the process and quality assurance criteria.

DOI: 10.7150/jca.13503

PMCID: PMC4679387

PMID: 26722366

Conflict of interest statement: Competing Interests: The authors have declared that no competing interest exists.

33. J Low Genit Tract Dis. 2016 Jan;20(1):11-4. doi: 10.1097/LGT.0000000000000169.

The 2015 International Society for the Study of Vulvovaginal Disease (ISSVD) Terminology of Vulvar Squamous Intraepithelial Lesions.

Bornstein J(1), Bogliatto F, Haefner HK, Stockdale CK, Preti M, Bohl TG, Reutter J; ISSVD Terminology Committee.

Collaborators: Bornstein J, Bogliatto F, Bohl TG, Coady D, Haefner HK, Preti M, Reutter J, Selva-Nayagam P, Stockdale CK, Van-Beurden M.

Author information:

(1)From the 1Department of Obstetrics and Gynecology, Galilee Medical Center and Bar-Ilan University Faculty of Medicine, Nahariya, Israel; 2Department of Obstetrics and Gynecology, Chivasso Civic Hospital, Chivasso, Turin, Italy; 3Department of Obstetrics and Gynecology, University of Michigan Health System, Ann Arbor, MI; 4Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA; 5Department of Obstetrics and Gynecology, University of Turin, Turin, Italy; 6Jean Hailes Medical Center for Women, Monash, Australia; and 7Piedmont Pathology Associates, Hickory, NC.

RESULTS: The final version accepted by the ISSVD contains the following:•Low-grade SIL of the vulva or vulvar LSIL, encompassing flat condyloma or human papillomavirus effect.•High-grade SIL or vulvar HSIL (which was termed “vulvar intraepithelial neoplasia usual type” in the 2004 ISSVD terminology).•Vulvar intraepithelial neoplasia, differentiated type.

CONCLUSIONS: The advantage of the new terminology is that it includes all types of vulvar SILs, it provides a solution to the concerns in relation to the application of LAST to vulvar lesion, and it is in accordance with the World Health Organization classification as well as the LAST, creating unity among clinicians and pathologists.

DOI: 10.1097/LGT.0000000000000169

PMID: 26704327 [Indexed for MEDLINE]

34. Ecancermedicalscience. 2015 Apr 29;9:533. doi: 10.3332/ecancer.2015.533. eCollection 2015.

E6/E7 mRNA testing for human papilloma virus-induced high-grade cervical intraepithelial disease (CIN2/CIN3): a promising perspective.

Origoni M(1), Cristoforoni P(2), Carminati G(1), Stefani C(1), Costa S(3), Sandri MT(4), Mariani L(5), Preti M(6).

Author information:

(1)Department of Gynaecology & Obstetrics, Vita Salute San Raffaele University, School of Medicine, Milano 20132, Italy.

(2)Polo Oncologico Villa Montallegro, Genova 16145, Italy.

(3)M.F. Toniolo Hospital, Bologna 40141, Italy.

(4)Division of Laboratory Medicine, European Institute of Oncology, Milano 20141, Italy.

(5)HPV-UNIT, Regina Elena National Cancer Institute, Roma 00144, Italy.

(6)Unit of Preventive Gynaecology, European Institute of Oncology, Milano 20141, Italy.

Since the introduction of biomolecular testing for the identification of high-risk human papillomavirus DNA (hrHPV-DNA) in cervical cancer preventive strategies, many interesting aspects have emerged in this field; firstly, HPV-DNA testing has been demonstrated to have better sensitivity than conventional cytology in several settings: screening, triage of ASC-US and in follow-up after treatment. Despite this, some limitations of these new technologies have also been underlined: the major issue is the low specificity of the tests, which cannot discriminate between regressive and progressive infections. Thus, recent research has moved the attention towards novel markers of progression that could more precisely detect cases at real risk of cancer development. In view of the fact that progression to cancer is dependable of the E6/E7 proteins integration and transforming action, the overexpression of E6/E7 transcripts has been seen as a valuable marker of this risk. This review aims to summarise the literature data on this topic and to provide a clear view of the emerging perspectives.

DOI: 10.3332/ecancer.2015.533

PMCID: PMC4435751

PMID: 26015802

35. Ecancermedicalscience. 2015 Apr 29;9:531. doi: 10.3332/ecancer.2015.531. eCollection 2015.

VIN usual type-from the past to the future.

Preti M(1), Igidbashian S(2), Costa S(3), Cristoforoni P(4), Mariani L(5), Origoni M(6), Sandri MT(7), Boveri S(2), Spolti N(2), Spinaci L(2), Sanvito F(2), Preti EP(2), Falasca A(2), Radici G(2), Micheletti L(8).

Author information:

(1)Preventive Gynecology Unit, European Institute of Oncology, Milano 20100, Italy ; The Italian HPV Study Group (IHSG).

(2)Preventive Gynecology Unit, European Institute of Oncology, Milano 20100, Italy.

(3)M.F. Toniolo Hospital, Bologna 40100, Italy ; The Italian HPV Study Group (IHSG).

(4)Villa Montallegro, Genova 16100, Italy ; The Italian HPV Study Group (IHSG).

(5)HPV-Unit Gynecologic Oncology, Regina Elena National Cancer Institute of Rome, Rome 00100, Italy ; The Italian HPV Study Group (IHSG).

(6)Department of Obstetrics and Gynecology, Vita Salute San Raffaele University School of Medicine, Milano 20100, Italy ; The Italian HPV Study Group (IHSG).

(7)Division of Laboratory Medicine, European Institute of Oncology, Milano 20100, Italy ; The Italian HPV Study Group (IHSG).

(8)Department of Obstetrics and Gynecology, University of Torino, Torino 10100, Italy.

Usual vulvar intraepithelial neoplasia (uVIN) is the most common VIN type, generally related to a human papillomavirus (HPV) infection, predominantly type 16. The incidence of uVIN has been increasing over the last decades, and a bimodal peak is observed at the age of 40-44 and over 55 years. Almost 40% of patients with uVIN have a past, concomitant or future HPV-associated lesion of the lower genital tract. HPV-related malignancies are associated with a persistent HPV infection. The host immune response is of crucial importance in determining clearance or persistence of both HPV infections and HPV-related VIN. About 60% of the patients present with symptoms. Clinical features of uVIN vary in site, number, size, shape, colour, and thickness of lesions. Multicentric disease is often present. Most uVIN lesions are positive at immunohistochemistry to p16(ink4a) and p14(arf), but negative to p53. Irrespective of surgical treatment used, uVIN recurrence rates are high. Positive margins do not predict the development of invasive disease and the need to re-excide the tissue around the scare remains to be demonstrated. Therefore, considering the low progression rate of uVIN and psycosexual sequelae, treatments should be as conservative as possible. Medical treatments available are mainly based on immunotherapy to induce normalisation of immune cell count in uVIN. None are approved by the food and drug administration (FDA) for the treatment of uVIN. If medical treatment is performed, adequate biopsies are required to reduce the risk of unrecognised invasive disease. Some studies suggest that failure to respond to immunotherapy might be related to a local immunosuppressive microenvironment, but knowledge of the uVIN microenvironment is limited. Moreover, our knowledge of the potential mechanisms involved in the escape of HPV-induced lesions from the immune system has many gaps. HPV vaccines have been demonstrated to be effective in preventing uVIN, with 94.9% efficacy in the HPV-naive population, while studies on therapeutic vaccines are limited. The low incidence of VIN requires large multicentre studies to determine the best way to manage affected patients and to investigate the immunological characteristics of the ‘vulvar microenviroment’ which leads to the persistence of HPV.

DOI: 10.3332/ecancer.2015.531

PMCID: PMC4431399

PMID: 25987900

36. Ecancermedicalscience. 2015 Apr 29;9:528. doi: 10.3332/ecancer.2015.528. eCollection 2015.

Performance of HPV DNA testing in the follow-up after treatment of high-grade cervical lesions, adenocarcinoma in situ (AIS) and microinvasive carcinoma.

Costa S(1), Venturoli S(2), Origoni M(3), Preti M(4), Mariani L(5), Cristoforoni P(6), Sandri MT(4).

Author information:

(1)Obstetrics & Gynaecology Unit, Policlinico S Orsola-Malpighi University Hospital, Bologna, Italy Present address: MF Toniolo Hospital, via Toscana, 42, Bologna 40138, Italy ; The Italian HPV Study Group (IHSG).

(2)Unit of Microbiology, Department of Diagnostic Medicine and Prevention, S Orsola-Malpighi Hospital, University of Bologna, Bologna 40138, Italy.

(3)Department of Obstetrics & Gynaecology, School of Medicine, Vita-Salute San Raffaele University, Milano 20132, Italy ; The Italian HPV Study Group (IHSG).

(4)Preventive Gynaecology Unit, European Institute of Oncology, Milano 20141, Italy ; The Italian HPV Study Group (IHSG).

(5)HPV Unit, Gynaecologic Oncology, Regina Elena National Cancer Institute of Rome, Rome 00144, Italy ; The Italian HPV Study Group (IHSG).

(6)National Institute on Cancer Research (IST), Genova 16132, Italy ; The Italian HPV Study Group (IHSG).

BACKGROUND: Over the last two decades it has become clear that distinct types of human papillomavirus (HPV), the so-called high-risk types (hrHPV), are the major cause of cervical cancer. The hrHPV-DNA testing has shown excellent performance in several clinical applications from screening to the follow-up of conservatively treated patients.

METHODS: We conducted a systematic review of the recent literature on the performance of HPV DNA testing in follow-up after treatment of high-grade cervical lesions, adenocarcinoma in situ, and microinvasive carcinoma compared to Pap smear cytology.

RESULTS: Observational studies have demonstrated that the high risk hrHPV-DNA test is significantly more sensitive (95%) compared to follow-up cytology(70%) in detecting post-treatment squamous intraepithelial high-grade lesions. Moreover, in patients treated conservatively for cervical adenocarcinoma in situ, the hrHPV-DNA test is the most significant independent predictor of recurrent disease or progression to invasive cancer, and the combination of viral DNA testing and cytology reaches 90% sensitivity in detecting persistent lesions at the first follow-up visit and 100% at the second follow-up visit. The cause of microinvasive squamous cervical carcinoma is increasingly treated with conservative therapies in order to preserve fertility, and an effective strategy allowing early detection of residual or progressive disease has become more and more important in post-treatment follow-up. Primary results seem to indicate that the median time for viral clearance is relatively longer compared with patients treated for CIN and suggest a prolonged surveillance for these patients. However, the potential clinical value of HPV-DNA testing in this clinical setting needs to be confirmed by further observations.

CONCLUSIONS: The excellent sensitivity, negative predictive value, and optimal reproducibility of the hrHPV DNA testing, currently is considered a powerful tool in the clinicians’ hands to better manage post-treatment follow-up either in cervical squamous lesion or in situ adenocarcinoma.

DOI: 10.3332/ecancer.2015.528

PMCID: PMC4431402

PMID: 25987897

37. Best Pract Res Clin Obstet Gynaecol. 2014 Oct;28(7):1074-87. doi: 10.1016/j.bpobgyn.2014.07.011. Epub 2014 Jul 22.

Surgery of the vulva in vulvar cancer.

Micheletti L(1), Preti M(2).

Author information:

(1)Department of Gynaecology and Obstetrics, University of Torino, Ospedale S. Anna, Via Ventimiglia 3, 10126 Torino, Italy. Electronic address: l.micheletti@libero.it.

(2)Department of Gynaecology and Obstetrics, University of Torino, Ospedale S. Anna, Via Ventimiglia 3, 10126 Torino, Italy. Electronic address: Mario.preti@tin.it.

The standard radical mutilating surgery for the treatment of invasive vulval carcinoma is, today, being replaced by a conservative and individualised approach. Surgical conservative modifications that are currently considered

safe, regarding vulval lesion, are separate skin vulval-groin incisions, drawn according to the lesion diameter, and wide local radical excision or partial radical vulvectomy with 1-2 cm of clinically clear surgical margins. Regarding inguinofemoral lymph nodes management, surgical conservative modifications not compromising patient survival are omission of groin lymphadenectomy only when tumour stromal invasion is ≤ 1 mm, unilateral groin lymphadenectomy only in well-lateralised early lesions and total or radical inguinofemoral lymphadenectomy with preservation of femoral fascia when full groin resection is needed. Sentinel lymph node dissection is a promising technique but it should not be routinely employed outside referral centres. Pelvic nodes are better managed by radiation. Locally advanced vulval carcinoma can be managed by ultraradical surgery, exclusive radiotherapy or chemoradiation.

DOI: 10.1016/j.bpobgyn.2014.07.011

PMID: 25132277 [Indexed for MEDLINE]

38. Best Pract Res Clin Obstet Gynaecol. 2014 Oct;28(7):1051-62. doi: 10.1016/j.bpobgyn.2014.07.010. Epub 2014 Jul 18.

Vulvar intraepithelial neoplasia.

Preti M(1), Scurry J(2), Marchitelli CE(3), Micheletti L(4).

Author information:

(1)Gynecological Oncologist, Department of Obstetrics and Gynecology, University of Turin, Via Ventimiglia 3, Turin, Italy. Electronic address: mario.preti@tin.it.

(2)Anatomical Pathologist, FRCPA, Anatomical Pathology, HAPS, New Lambton, NSW 2305, Australia. Electronic address: jim.scurry@hnehealth.nsw.gov.au.

(3)Chief Unit of Vulvar Diseases, Department of Gynecology, Hospital Italiano, Pavón 4239, Capital Federal, Buenos Aires, Argentina. Electronic address: claudia.marchitelli@hospitalitaliano.org.ar.

(4)Associated Professor, Department of Obstetrics and Gynecology, University of Turin, Via Ventimiglia 3, Turin, Italy. Electronic address: l.micheletti@libero.it.

Vulvar intraepithelial neoplasia (VIN) is a high-grade intraepithelial squamous lesion and precursor of invasive squamous cell carcinoma (SCC). The 2004 International Society for the Study of Vulvovaginal Disease (ISSVD) classification distinguished two types of VIN: usual type (human papillomavirus (HPV)-related) and differentiated type (not HPV-related). The incidence of usual-type VIN is higher in younger women, while differentiated-type VIN is more common in older patients with chronic dermatologic conditions. Differentiated-type VIN has a greater invasive potential and shorter time between diagnosis and SCC than usual-type VIN. The diagnosis of VIN is carried out by identifying a lesion by visual inspection and confirming by performing a biopsy. Screening tests are not available. Patients with usual-type VIN are at a higher risk of developing another HPV-related malignancy of the anogenital tract; therefore, examination from the cervix to the perianal area is mandatory. The therapeutic approach to VIN balances the invasive potential with the need to be as conservative as possible. Current prophylactic HPV vaccines offer protection against usual-type VIN and related invasive carcinoma.

DOI: 10.1016/j.bpobgyn.2014.07.010

PMID: 25106700 [Indexed for MEDLINE]

39. Arch Gynecol Obstet. 2014 May;289(5):1053-60. doi: 10.1007/s00404-013-3104-5. Epub 2013 Dec 4.

Advanced utero-vaginal prolapse and vaginal vault suspension: synthetic mesh vs native tissue repair.

Cosma S(1), Menato G, Preti M, Petruzzelli P, Tin MC, Riboni F, Benedetto C.

Author information:

(1)Department of Gynecology and Obstetrics, Sant’ Anna Hospital, University of Turin, Via Ventimiglia 3, 10126, Turin, Italy, cosmastefano@libero.it.

PURPOSE: To compare prosthetic and ligament vaginal vault suspension at vaginal hysterectomy in patients, with utero-vaginal stage III-IV pelvic organ prolapse quantification.

METHODS: A retrospective case-control study was designed to compare 61 patients who had undergone Posterior intravaginal slingplasty (PIVS) with 61 patients in a matched control group who had undergone uterosacral ligament suspension (ULS). The primary outcome was to compare anatomic vaginal vault failure rate. The secondary outcomes were subjective cure and cure without adverse events.

RESULTS: Follow-up mean duration for the PIVS and ULS groups was 56.2 and 57.7 months, respectively. Recurrent vault prolapse was observed more frequently in the ULS group with pre-intervention stage IV prolapse (0 vs 14.8 %; p = 0.04), while there was no difference in prolapse recurrence at any vaginal site. Although the subjective cure of PIVS and ULS was superimposable (91.8 vs 86.9 %; p = 0.25), there was a significantly higher cure rate, without adverse events, in the ULS group (90.2 vs 100 %; p = 0.01).

CONCLUSIONS: Non-mesh vaginal vault repair should be considered the first-line measure at vaginal hysterectomy; prosthetic repair should be used for therapeutic purposes in patients with vaginal vault recurrence and considered at vaginal hysterectomy only in selected subjects with complete utero-vaginal eversion.

DOI: 10.1007/s00404-013-3104-5

PMID: 24305747 [Indexed for MEDLINE]

40. Int Urogynecol J. 2013 Dec;24(12):2125-30. doi: 10.1007/s00192-013-2134-7. Epub 2013 Jul 25.

Psychometric validation of the Italian version of the I-QoL questionnaire: clinical and urodynamic findings.

Possavino F(1), Preti M, Carone R, Calabrese R, Randaccio S, D’Elia C, Allais I, Cosma S, Benedetto C.

Author information:

(1)Department of Obstetrics and Gynecology, University of Turin, Corso Siracusa 188, 10137, Turin, Italy, federica.possavino@virgilio.it.

INTRODUCTION AND HYPOTHESIS: The aim was to validate the Italian version of the Incontinence-Quality of Life questionnaire (I-QoL) in women with clinical and urodynamic urinary incontinence (UI). A secondary end point was to compare the results of women with reported UI, but negative urodynamic findings.

METHODS: The Italian translation of the I-QoL was administered to 267 Italian women with pelvic organ prolapse < stage III, and who had undergone previous surgical or medical therapy for UI. Cronbach’s alpha was calculated to assess internal consistency of the I-QoL items. Reproducibility was assessed using the intraclass correlation coefficient (ICC). Convergent validity involved comparison of I-QoL scores and the Short Form-36 Health questionnaire.

RESULTS: One hundred and sixty-seven patients were considered for the primary end point: 47 had a negative history of UI and a normal urodynamic test, 120 complained of UI confirmed by a urodynamic test, 59 had a positive history for UI and a urodynamic test negative for UI, and 35 patients not reporting UI had a positive urodynamic test. The I-QoL score revealed that the QoL was lower in patients with reported UI, irrespective of urodynamic findings. The overall I-QoL summary score and subscales showed high internal consistency (alpha ranges from 0.88 to 0.96). ICC ranged from 0.98 to 0.99, demonstrating the stability of the scores. The physical domain of the I-QoL showed a 0.27 correlation with the physical functioning subscale of the SF-36. No significant difference in I-QoL scores was found among various types of UI.

CONCLUSION: The Italian translated version of the I-QoL is reliable, consistent and a valid instrument for assessing impact on quality of life in Italian speaking women with UI.

DOI: 10.1007/s00192-013-2134-7

PMID: 23884377 [Indexed for MEDLINE]

41. J Low Genit Tract Dis. 2013 Jul;17(3):362-5. doi: 10.1097/LGT.0b013e31826f24c0.

Human papillomavirus DNA and Pap tests: the need for cotesting in opportunistic setting during the transition time.

Mariani L, Sideri M, Costa S, Cristoforoni P, Origoni M, Preti M; Italian HPV Study Group.

DOI: 10.1097/LGT.0b013e31826f24c0

PMID: 23552207 [Indexed for MEDLINE]

42. Gynecol Oncol. 2012 Mar;124(3):490-5. doi: 10.1016/j.ygyno.2011.11.039. Epub 2011 Dec 1.

Factors predicting the outcome of conservatively treated adenocarcinoma in situ of the uterine cervix: an analysis of 166 cases.

Costa S(1), Venturoli S, Negri G, Sideri M, Preti M, Pesaresi M, Falasca A, Barbieri D, Zerbini M, Santini D, Sandri MT, Ghiringhello B, Caroppo Venturini N, Syrjänen S, Syrjänen K.

Author information:

(1)Department of Obstetrics and Gynecology, S.Orsola-Malpighi University Hospital, Bologna, Italy.

OBJECTIVE: The present study assessed the clinical outcome of patients conservatively treated for cervical adenocarcinoma in situ (AIS) and their predictive factors using univariate and multivariate population averaged (PA) generalized estimating equation (GEE) model in a longitudinal setting.

METHODS: A series of 166 consecutive women (mean age 39.8 yrs; range 23-63 yrs) underwent conservative treatment of AIS as the primary treatment and were followed-up (mean 40.9 mo) using colposcopy, PAP-smear, biopsy and HPV-testing with Hybrid Capture 2.

RESULTS: Hysterectomy was performed as part of the primary management in 47 patients, who were excluded from the follow-up (FU) analysis. Out of 119 women closely followed-up, additional therapeutic procedures were performed in 69. At study conclusion, 7 patients (5.9%) showed persistent disease, while 8 (6.7%) had progressed to invasive adenocarcinoma (AC). Positive HR-HPV test was the only independent predictor of disease recurrence (adjusted OR=2.72; 95%CI 1.08-6.87), and together with free cone margins (OR=0.20; 95%CI 0.04-0.92), HR-HPV positivity was also the single most powerful predictor of disease progression to AC, with OR=3.74; 95%CI 1.84-7.61 (p=0.0001) in multivariate PA-GEE.

CONCLUSIONS: These results suggest that testing HR-HPV positive at any time point during FU is the most significant independent predictor of progressive disease, while showing free margins in cone has a significant protective effect against progression to AC. Furthermore, because 4.3% women with persistent, recurrent or progressive disease experienced a late (5th and 6th FU) diagnosis of HG-CGIN or microinvasive AC, a close surveillance should be scheduled for at least three years in conservatively treated AIS patients.

DOI: 10.1016/j.ygyno.2011.11.039

PMID: 22188786 [Indexed for MEDLINE]

43. Int Urogynecol J. 2011 May;22(5):611-9. doi: 10.1007/s00192-010-1350-7. Epub 2011 Jan 14.

Posterior intravaginal slingplasty: efficacy and complications in a continuous series of 118 cases.

Cosma S(1), Preti M, Mitidieri M, Petruzzelli P, Possavino F, Menato G.

Author information:

(1)Department of Gynecology and Obstetrics, University of Turin, Turin, Italy. cosmastefano@libero.it

INTRODUCTION AND HYPOTHESIS: Posterior intravaginal slingplasty (PIVS) is a minimally invasive procedure that aims to suspend vaginal vault. Our study evaluated efficacy and complications of PIVS at long-term follow-up.

METHODS: One hundred eighteen consecutive women underwent PIVS operation for Pelvic Organ Prolapse Quantification stage 3 or 4 vaginal cuff prolapse (VCP; 25 patients) or utero-vaginal prolapse (UVP; 93 patients). Apical vaginal wall at stage 0 or 1 was considered as cured.

RESULTS: Follow-up mean duration was 58.6 months (range, 24-84 months). The success rate of PIVS was 96.6%. Some 8.5% mesh erosion (20% in patients with VCP and 5.4% with UVP), 2.5% vaginal-perineal fistula, and 3.4% paravaginal hematoma occurred. Neither erosion nor fistulas occurred with monofilament polypropylene mesh.

CONCLUSION: PIVS seems a safe and effective procedure for VCP and UVP. Vaginal erosion was mainly observed in patients with VCP treated with multifilament polypropylene mesh.

DOI: 10.1007/s00192-010-1350-7

PMID: 21234547 [Indexed for MEDLINE]

44. J Low Genit Tract Dis. 2010 Oct;14(4):363-73. doi: 10.1097/LGT.0b013e3181d95c71.

Update on intraepithelial neoplasia of the vulva: proceedings of a Workshop at the 2009 World Congress of the International Society for the Study of Vulvovaginal Diseases, Edinburgh, Scotland, September 2009.

Heller DS(1), van Seters M, Marchitelli C, Moyal-Barracco M, Preti M, van Beurden M.

Author information:

(1)Department of Pathology and Laboratory Medicine, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA. hellerds@umdnj.edu

A workshop on updates on intraepithelial neoplasia of the vulva was held at the 2009 World Congress of the International Society for the Study of Vulvovaginal Diseases in Edinburgh, Scotland, September 2009. This is a review of the information presented.

DOI: 10.1097/LGT.0b013e3181d95c71

PMID: 20885166 [Indexed for MEDLINE]

45. Eur J Cancer. 2009 Aug;45(12):2212-8. doi: 10.1016/j.ejca.2009.05.003. Epub 2009 May 26.

Pluripotent factor lin-28 and its homologue lin-28b in epithelial ovarian cancer and their associations with disease outcomes and expression of let-7a and IGF-II.

Lu L(1), Katsaros D, Shaverdashvili K, Qian B, Wu Y, de la Longrais IA, Preti M, Menato G, Yu H.

Author information:

(1)Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, 60 College Street, New Haven, CT 06520-8034, USA.

Lin-28 and lin-28B are RNA-binding proteins which can block microRNA let-7 maturation and affect the differentiation and proliferation of embryonic stem cells. Lin-28 may also regulate the expression of insulin-like growth factor II (IGF-II). As one of the pluripotent factors involved in making induced pluripotent stem cells (iPS), lin-28 is considered a potential therapeutic target for cancer treatment. To further understand the role of lin-28 in cancer, we analysed the expression of lin-28 and its homologue lin-28B in tumour samples, and evaluated their associations with let-7a maturation, IGF-II expression, disease features and outcomes in 211 patients with primary epithelial ovarian cancer. The analysis showed that both lin-28 and lin-28B were positively correlated with primary and pre-let-7a-3; lin-28B, not lin-28, was inversely correlated with mature let-7a. A positive correlation was also observed between lin-28B and IGF-II expression, while no association was found between lin-28B and IGF-I or IGFBP-3. The study further demonstrated that lin-28B expression was associated with the risk of disease progression and death; patients with high lin-28B had shorter progression-free and overall survival than those with low lin-28B. These results seem to support the findings of recent in vitro experiments, showing that lin-28 blocks the process of let-7a maturation. Our study also suggests that lin-28B may promote ovarian cancer progression and serve as an unfavourable prognostic marker for the disease. The correlation between lin-28B and IGF-II indicates that the growth factor may mediate the effect of lin-28B on tumour growth.

DOI: 10.1016/j.ejca.2009.05.003

PMID: 19477633 [Indexed for MEDLINE]

46. Cancer. 2009 Jun 1;115(11):2453-63. doi: 10.1002/cncr.24282.

Stathmin and tubulin expression and survival of ovarian cancer patients receiving platinum treatment with and without paclitaxel.

Su D(1), Smith SM, Preti M, Schwartz P, Rutherford TJ, Menato G, Danese S, Ma S, Yu H, Katsaros D.

Author information:

(1)Research Institute, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.

BACKGROUND: Paclitaxel interacts with microtubules to exert therapeutic effects. Molecules that affect microtubule activity, such as betaIII-tubulin and stathmin, may interfere with the treatment. In this study, the authors analyzed betaIII-tubulin and stathmin expression in ovarian tumors and examined their associations with treatment response and patient survival.

METHODS: The study included 178 patients with epithelial ovarian cancer who underwent cytoreductive surgery followed by platinum-based chemotherapy; of these patients, 75 also received paclitaxel. Fresh tumor samples that were collected at surgery were analyzed for messenger RNA expression of betaIII-tubulin and stathmin using real-time polymerase chain reaction analysis. Associations of these molecules with treatment response, disease progression, and overall survival were evaluated.

RESULTS: High stathmin expression was associated with worse disease progression-free and overall survival compared with low stathmin expression. This association was independent of patient age, disease stage, tumor grade, histology, and residual tumor size and was observed in patients who received platinum plus paclitaxel, but not in patients who received platinum without paclitaxel, suggesting that stathmin expression in tumor tissue may interfere with paclitaxel treatment. Similar effects were not observed for betaIII-tubulin, although high betaIII-tubulin expression was associated with disease progression among patients who received platinum without paclitaxel. No associations were observed between treatment response and tubulin or stathmin expression. Expression levels of betaIII-tubulin and stathmin were correlated significantly.

CONCLUSIONS: High stathmin expression predicted an unfavorable prognosis in patients with ovarian cancer who received paclitaxel and platinum chemotherapy. This finding supports the possibility that stathmin may interfere with paclitaxel treatment, leading to a poor prognosis for patients with ovarian cancer.

DOI: 10.1002/cncr.24282

PMID: 19322891 [Indexed for MEDLINE]

47. Breast Cancer Res Treat. 2009 Sep;117(1):131-40. doi: 10.1007/s10549-008-0219-7. Epub 2008 Oct 19.

High miR-21 expression in breast cancer associated with poor disease-free survival in early stage disease and high TGF-beta1.

Qian B(1), Katsaros D, Lu L, Preti M, Durando A, Arisio R, Mu L, Yu H.

Author information:

(1)Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520-8034, USA.

MicroRNA-21 (miR-21) is considered an onco-microRNA given its abilities to suppress the actions of several tumor suppressor genes and to promote tumor cell growth, invasion and metastasis. Recently, transforming growth factor-beta (TGF-beta) is found to up-regulate the expression of miR-21, and elevated miR-21 expression is seen frequently in breast cancer. To evaluate the effect of miR-21 on disease progression and its association with TGF-beta, we analyzed miR-21 expression in breast cancer. Fresh tumor samples were collected during surgery from 344 patients diagnosed with primary breast cancer. The expression of miR-21 in tumor samples was measured with a TaqMan microRNA assay using U6 as reference. Levels of miR-21 expression by disease stage, tumor grade, histology, hormone receptor status and lymph node involvement were compared. Cox proportional hazards regression analysis was performed to assess the association of miR-21 expression with disease-free and overall survival. The study results showed that the expression of miR-21 was detected in all tumor samples with substantial variation. High miR-21 expression was associated with features of aggressive disease, including high tumor grade, negative hormone receptor status, and ductal carcinoma. High miR-21 was also positively correlated with TGF-beta1. No associations were found between patient survival and miR-21 expression among all patients, but high miR-21 was associated with poor disease-free survival in early stage patients (HR = 2.08, 95% CI: 1.08-4.00) despite no value for prognosis. The study supports the notion that miR-21 is an onco-microRNA for breast cancer. Elevated miR-21 expression may facilitate tumor progression, and TGF-beta may up-regulate its expression.

DOI: 10.1007/s10549-008-0219-7

PMID: 18932017 [Indexed for MEDLINE]

48. Br J Cancer. 2008 Oct 21;99(8):1357-63. doi: 10.1038/sj.bjc.6604689. Epub 2008 Sep 30.

TGF-beta1 genotype and phenotype in breast cancer and their associations with IGFs and patient survival.

Mu L(1), Katsaros D, Lu L, Preti M, Durando A, Arisio R, Yu H.

Author information:

(1)Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520-8034, USA.

Transforming growth factor-beta (TGF-beta)-mediated signals play complicated roles in the development and progression of breast tumour. The purposes of this study were to analyse the genotype of TGF-beta1 at T29C and TGF-beta1 phenotype in breast tumours, and to evaluate their associations with IGFs and clinical characteristics of breast cancer. Fresh tumour samples were collected from 348 breast cancer patients. TGF-beta1 genotype and phenotype were analysed with TaqMan and ELISA, respectively. Members of the IGF family in tumour tissue were measured with ELISA. Cox proportional hazards regression analysis was performed to assess the association of TGF-beta1 and disease outcomes. Patients with the T/T (29%) genotype at T29C had the highest TGF-beta1, 707.9 pg mg(-1), followed by the T/C (49%), 657.8 pg mg(-1), and C/C (22%) genotypes, 640.8 pg mg(-1), (P=0.210, T/T vs C/C and C/T). TGF-beta1 concentrations were positively correlated with levels of oestrogen receptor, IGF-I, IGF-II and IGFBP-3. Survival analysis showed TGF-beta1 associated with disease progression, but the association differed by disease stage. For early-stage disease, patients with the T/T genotype or high TGF-beta1 had shorter overall survival compared to those without T/T or with low TGF-beta1; the hazard ratios (HR) were 3.54 (95% CI: 1.21-10.40) for genotype and 2.54 (95% CI: 1.10-5.89) for phenotype after adjusting for age, grade, histotype and receptor status. For late-stage disease, however, the association was different. The T/T genotype was associated with lower risk of disease recurrence (HR=0.13, 95% CI: 0.02-1.00), whereas no association was found between TGF-beta1 phenotype and survival outcomes. The study suggests a complex role of TGF-beta1 in breast cancer progression, which supports the finding of in vitro studies that TGF-beta1 has conflicting effects on tumour growth and metastasis.

DOI: 10.1038/sj.bjc.6604689

PMCID: PMC2570529

PMID: 18827819 [Indexed for MEDLINE]

49. Gynecol Oncol. 2008 Jul;110(1):83-6. doi: 10.1016/j.ygyno.2008.03.001. Epub 2008 Apr 24.

A suggested modification to FIGO stage III vulvar cancer.

Rouzier R(1), Preti M, Sideri M, Paniel BJ, Jones RW.

Author information:

(1)Department of Gynecology, UPMC University Paris 06, UPRES EA 4053, F-75005, Paris, France. rouzierroman@yahoo.fr

OBJECTIVE: FIGO Stage III vulvar cancer includes tumors that invade the lower urethra, vagina, or anus, and/or tumors that have metastasized to the inguino-femoral lymph nodes of one groin. We hypothesized that locally advanced stage III vulvar cancer and regional metastatic stage III vulvar cancer (lymph node involvement) have different prognoses.

METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) registry public use data tapes, we identified patients diagnosed with vulvar carcinoma from 1988 through 2004. Overall survival (OS) was measured as the time from diagnosis to the date of death or last follow-up. We used the Kaplan-Meier method to estimate OS and the log-rank test to assess for differences between patient groups. The staging performance was quantified with respect to discrimination.

RESULTS: The study cohort included 895 patients. The survival difference between stage III patients with locally advanced vulvar cancer and stage III patients with regional metastatic node(s) disease was highly significant (P<10(-10)). The 5-year and 10-year OS of patients with locally advanced vulvar tumors without metastatic nodes were 62% and 47%, respectively. The 5-year and 10-year OS of patients with regional metastatic node(s) disease were 39% and 27%, respectively. Separating locally advanced stage III and regional metastatic stage III disease would improve discrimination (concordance index: 72% vs 69% with the actual staging system).

CONCLUSION: Involvement of the inguinal lymph nodes in FIGO (1988) stage III patients carries a significantly worse prognosis compared with invasion of the lower urethra, vagina or anus alone. This difference in prognosis would favor restaging these two entities.

DOI: 10.1016/j.ygyno.2008.03.001

PMID: 18436291 [Indexed for MEDLINE]

50. Eur J Gynaecol Oncol. 2008;29(1):52-6.

Migrant women and cervical cancer: background of a prevention study.

Mariani L(1), Morrone A, Preti M, Sbiroli C, Tomao F, Tomao S.

Author information:

(1)Department Gynecologic Oncology, Regina Elena Cancer Institute of Rome, Italy. luciorm@libero.it

The study was scheduled in order to organize a program of prevention against cervical cancer in female migrants in Rome, and therefore to facilitate access to appropriate preventive oncological facilities for discriminated women. Moreover, the study will also investigate the risk factors and social conditions

(HPV-subtypes, sexual behavior, smoking habits) of such women since their migration to Italy. This is scientific and cultural background of a longitudinal, observational study on the cervical cancer risk in Roman migrant population. By means of a mother language questionnaire (with the presence of a cultural mediator) it will be possible to achieve data on social conditions and the new life-style. An HPV-testing (HC2) combined with Pap-test (with further genotype distribution) will be performed in all women enrolled in the study. Further diagnostic/therapeutic decisions will depend on the results of both tests. Scientific results are expected in the next two years, but an increasing of cancer prevention awareness among female migrant populations is expected from the beginning of the program. The present study was aimed at culturally appropriate intervention strategies to limit the disparities that migrants usually suffer in most of the developed Western nations in respect to the native counterparts.

PMID: 18386464 [Indexed for MEDLINE]

51. Am J Surg Pathol. 2007 Sep;31(9):1452; author reply 1452–4. doi: 10.1097/PAS.0b013e31804c9883.

Comment on the Article: Srodon M, Stoler MH, Baber GB, et al. The distribution of low and high-risk HPV types in vulvar and vaginal intraepithelial neoplasia (VIN and VaIN) Am J Surg Pathol. 2006;30:1513-1518.

Sideri M, Jones RW, Heller DS, Haefner H, Neill S, Preti M, Scurry J, Wilkinson EJ, Edwards L.

Comment on

Am J Surg Pathol. 2006 Dec;30(12):1513-8.

DOI: 10.1097/PAS.0b013e31804c9883

PMID: 17721204 [Indexed for MEDLINE]

52. J Low Genit Tract Dis. 2003 Apr;7(2):122-35. doi: 10.1097/00128360-200304000-00009.

Vulvar Paget disease: one century after first reported.

Preti M(1), Micheletti L, Massobrio M, Ansai S, Wilkinson EJ.

Author information:

(1)1Department of Gynecology and Obstetrics, University of Turin, Turin, Italy; 2Department of Dermatology, Akita University School of Medicine, Akita City, Japan; and 3Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL.

OBJECTIVES.: To provide a critical assessment of the published literature on vulvar Paget disease and to allow individualized approaches to affected patients. MATERIALS AND METHODS.: A computerized search for studies published in the literature up to June 2002 was carried out using Ovid(c) and Medline databases. We excluded single case reports, letters to editors, and abstracts. RESULTS.: Historical and epidemiological aspects of vulvar Paget disease are summarized. Clinical and histopathological data support a recent proposal to classify vulvar Paget disease into two categories, primary and secondary, with significant clinical and prognostic implications. The treatment for primary vulvar Paget disease is wide and deep surgical excision. Inguinofemoral lymphadenectomy is added in the management of invasive neoplasms. In the presence of secondary Paget disease, therapy must be directed toward treatment of associated carcinoma. CONCLUSIONS.: The subclassification of vulvar Paget disease is essential for correct clinical management and treatment. Immunohistochemistry may assist in this important distinction.

DOI: 10.1097/00128360-200304000-00009

PMID: 17051057

53. Gynecol Oncol. 2006 Oct;103(1):375-6; author reply 376-7. doi: 10.1016/j.ygyno.2006.07.001. Epub 2006 Aug 7.

Stage 1A squamous cell carcinoma of the vulva.

Preti M, Rouzier R, Mariani L.

Comment on

Gynecol Oncol. 2006 Apr;101(1):172-4.

DOI: 10.1016/j.ygyno.2006.07.001

PMID: 16890982 [Indexed for MEDLINE]

54. Obstet Gynecol. 2006 Mar;107(3):672-7. doi: 10.1097/01.AOG.0000198639.36855.e9.

Development and validation of a nomogram for predicting outcome of patients with vulvar cancer.

Rouzier R(1), Preti M, Haddad B, Martin M, Micheletti L, Paniel BJ.

Author information:

(1)Department of Gynecology and Obstetrics, Centre Hospitalier Intercommunal de Créteil, University Paris 12, Créteil, France. rouzierroman@yahoo.fr

OBJECTIVE: To construct and validate a nomogram to predict relapse-free survival of patients treated for vulvar cancer.

METHODS: Data from 244 patients treated for vulvar cancer at a single institution (Creteil, France) were used as a training set to develop and calibrate a nomogram for predicting relapse-free survival and local relapse-free survival. We used bootstrap resampling for the internal validation and we tested the nomogram on an independent validation set of patients (Torino, Italy) for the external validation.

RESULTS: The nomograms were based on a Cox proportional hazards regression model. Covariates for the relapse-free survival model included age, T stage,

number of metastatic nodes, bilateral lymph node involvement, omission of the lymphadenectomy, margin status, lymphovascular space invasion, and depth of invasion. The concordance indices were 0.85 and 0.83 in the training set before and after bootstrapping, respectively, and 0.83 in the validation set. The predictions of our nomogram discriminated better than did the International Federation of Gynecology and Obstetrics stage (0.83 compared with 0.78, P = .01). The calibration of our nomogram was good. In the validation set, 2-year and 5-year relapse-free survival were well predicted with less than 5% difference between the predicted and observed survivals for each quartile. A nomogram for predicting local relapse was also developed.

CONCLUSION: We have developed nomograms for predicting distant and local relapse of vulvar cancer at 2 and 5 years and validated them both internally and externally. These nomograms will be freely available on the International Society for the Study of Vulvovaginal Disease Web site.

LEVEL OF EVIDENCE: III.

DOI: 10.1097/01.AOG.0000198639.36855.e9

PMID: 16507940 [Indexed for MEDLINE]

55. J Reprod Med. 2005 Nov;50(11):807-10.

Squamous vulvar intraepithelial neoplasia: 2004 modified terminology, ISSVD Vulvar Oncology Subcommittee.

Sideri M(1), Jones RW, Wilkinson EJ, Preti M, Heller DS, Scurry J, Haefner H, Neill S.

Author information:

(1)European Institute of Oncology, Milan, Italy.

In the current classification, squamous vulvar intraepithelial neoplasia (VIN) is categorized as VIN 1, 2 and 3 according to the degree of abnormality. There is neither evidence that the VIN 1-3 morphologic spectrum reflects a biologic continuum nor that VIN 1 is a cancer precursor. The VIN 2 and 3 category includes 2 types of lesion, which differ in morphology, biology and clinical features. VIN, usual type (warty, basaloid and mixed), is HPV related in most cases. Invasive squamous carcinomas of warty or basaloid type is associated with VIN, usual type. VIN, differentiated type, is seen particularly in older women with lichen sclerosus and/or squamous cell hyperplasia in some cases. Neither VIN, differentiated type, nor associated keratinizing squamous cell carcinoma is HPV related. The term VIN should apply only to histologically high grade squamous lesions (former terms, VIN 2 and VIN 3 and differentiated VIN 3). The term VIN 1 will no longer be used. Two categories should describe squamous VIN: VIN, usual type (encompassing former VIN 2 and 3 of warty, basaloid and mixed types) and VIN, differentiated type (VIN 3, differentiated type).

PMID: 16419625 [Indexed for MEDLINE]

56. Clin Obstet Gynecol. 2005 Dec;48(4):862-8. doi: 10.1097/01.grf.0000179668.14187.3a.

Superficially invasive carcinoma of the vulva: diagnosis and treatment.

Preti M(1), Rouzier R, Mariani L, Wilkinson EJ.

Author information:

(1)Department of Obstetrics and Gynecology, University of Torino, Torino, Italy. mario.preti@tin.it

DOI: 10.1097/01.grf.0000179668.14187.3a

PMID: 16286832 [Indexed for MEDLINE]

57. Clin Obstet Gynecol. 2005 Dec;48(4):845-61. doi: 10.1097/01.grf.0000181738.37911.03.

Squamous vulvar intraepithelial neoplasia.

Preti M(1), Van Seters M, Sideri M, Van Beurden M.

Author information:

(1)Department of Obstetrics and Gynaecology, University of Torino, Torino, Italy. mario.preti@tin.it

DOI: 10.1097/01.grf.0000181738.37911.03

PMID: 16286831 [Indexed for MEDLINE]

58. J Reprod Med. 2002 Sep;47(9):715-7.

Vulvology. A proposal for a multidisciplinary subspecialty.

Micheletti L(1), Preti M, Bogliatto F, Lynch PJ.

Author information:

(1)Department of Gynecology and Obstetrics, University of Turin, Turin, Italy.

OBJECTIVE: To underline the usefulness of a new multidisciplinary subspecialty devoted entirely to vulvar diseases, to be termed vulvology.

STUDY DESIGN: Disorders of the vulva present a wide spectrum of clinical appearance, rendering clinical diagnosis difficult, if not impossible. The three types of physicians usually involved in treating the vulva (generalists, dermatologists and gynecologists) receive little training in and have little experience with vulvar problems. The end result is that women today are receiving far less than optimal care for vulvar disorders.

RESULTS: This situation can be much improved through the establishment of vulvology as a new multidisciplinary subspecialty. Vulvology can become a neutral field for research and debate and can provide a point of consolidation for all clinical care (infectious, metabolic, oncologic, neurologic, psychological, etc.) of vulvar disorders. The interdisciplinary nature of this new subspecialty will also facilitate the standardization and systematization of the currently confusing terminology and classification applicable to vulvar disorders.

CONCLUSION: Vulvology, as a new, well-defined, multidisciplinary subspecialty, will improve the care of women with vulvar problems through the delineation of

vulvologists as physicians with special expertise in this area, the establishment of clinics devoted specifically to the care of vulvar problems and the provision of education for physicians, other health care providers and the public.

PMID: 12380451 [Indexed for MEDLINE]

59. J Surg Oncol. 2002 Sep;81(1):19-24. doi: 10.1002/jso.10133.

Rationale and definition of the lateral extension of the inguinal lymphadenectomy for vulvar cancer derived from an embryological and anatomical study.

Micheletti L(1), Levi AC, Bogliatto F, Preti M, Massobrio M.

Author information:

(1)Department of Gynaecology and Obstetrics, University of Torino, Torino, Italy. l.micheletti@libero.it

BACKGROUND AND OBJECTIVES: The objective of the present study was to define the location of the most lateral superficial inguinal node lying along the inguinal ligament, through an embryological and anatomotopographical study, in order to rationalize the lateral extension of the groin lymphadenectomy in vulvar cancer.

METHODS: Sections of the upper portion of the femoral triangle belonging to three human fetuses, whose crown-rump (CR) length ranged from 70 to 310 mm, corresponding to a developmental age of 11 and 35 weeks, were studied. In addition, for an objective topographical evaluation of the disposition of the superficial inguinal lymph nodes, adult cadavers photographs of dissected Scarpa’s triangle, reported in anatomical atlases, were analyzed.

RESULTS: Both the embryological investigation and the anatomotopographical evaluation on cadavers photographs demonstrate that the most lateral superficial inguinal lymph node does not rise above the medial margin of the sartorius muscle, nor far lateral to the point where the superficial circumflex iliac vessels cross the inguinal ligament.

CONCLUSIONS: On the basis of the present study, the authors believe that the superficial circumflex iliac vessels could represent the lateral surgical landmark, easily detectable, at which the inguinal lymphadenectomy should cease. Therefore, there is no need to extend the lateral excision to the anterior superior iliac spine. Finally, leaving the fatty tissue laterally to these vessels, some lymphatic channels could be preserved, decreasing the incidence and the entity of wound seroma and lymphedema.

DOI: 10.1002/jso.10133

PMID: 12210022 [Indexed for MEDLINE]

60. Minerva Ginecol. 2000 Dec;52(12 Suppl 1):87-91.

[Vestibular papillomatosis].

[Article in Italian]

Micheletti L(1), Preti M, Bogliatto F, Chieppa P.

Author information:

(1)Dipartimento di Discipline Ginecologiche ed Ostetriche, Università di Torino.

The aim of the present study is to re-update the clinical significance of vestibular papillomatosis. At the beginning of the eighties this condition has been related to HPV infection based on histological and/or molecular evidence of the virus presence and considered responsible of many cases of pruritus and/or vulvodynia. Based upon these findings a lot of clinicians have been treating this condition by laser ablation or by topical application of podophyllin or trichloroacetic acid. At present the majority of the authors believes that vestibular papillomatosis should be considered an anatomical variant of the vestibular mucosa not HPV related. Therefore HPV-DNA presence should be considered a causal rather than a causal agent. This evidence is important in defining the management of vestibular papillomatosis: the papillae are usually distinguishable from condylomata acuminata by clinical examination and biopsies or HPV testing are not necessary. According to the studies considering vestibular papillomatosis a non HPV related condition and on the bases of a series of 252 women examined, the Authors share the opinion that this clinical entity should be considered a normal vestibular findings. As a consequence no ablative treatment is usually required even if in presence of symptomatology or HPV molecular infection.

PMID: 11526695 [Indexed for MEDLINE]

61. Br J Dermatol. 2000 Dec;143(6):1349-50. doi: 10.1046/j.1365-2133.2000.03935.x.

Vulval lichen planus in the practice of a vulval clinic.

Micheletti L, Preti M, Bogliatto F, Zanotto-Valentino MC, Ghiringhello B, Massobrio M.

DOI: 10.1046/j.1365-2133.2000.03935.x

PMID: 11122067 [Indexed for MEDLINE]

62. Minerva Ginecol. 2000 May;52(5):203-11.

[Vulvar Paget’s disease. Clinico-pathologic review of the literature].

[Article in Italian]

Preti M(1), Micheletti L, Ghiringhello B, Privitera S, Condello V, Chieppa P, Massobrio M.

Author information:

(1)Dipartimento di Discipline Ginecologiche ed Ostetriche, Università degli Studi, Torino. mario.preti@tin.it

In 1986 the International Society For the Study of Vulvar Disease classified vulvar Paget’s disease (VPD) as a non-squamous intraepithelial lesion of the vulva. The clinical multiform aspect of VPD, similar to other dermatological lesions, often delays the execution of a biopsy. Paget’s cells could be instead easily identified at histological examination and with histochemical reactions. Underlying adenocarcinomas or stromal invasion are present in about 10% of intraepithelial VPD. Patients with VPD are at risk for a second synchronous or metachronous neoplasia: colo-rectal adenocarcinoma (more frequent in perianal localization of VPD), cervical adenocarcinoma, carcinoma of the transitional epithelium from the renal pelvis to urethra and mammary carcinoma. A wide spectrum of frequency of these associations is reported in the literature (0-45%). Therapy for intraepithelial VPD is wide and deep surgical resection comprising all the skin appendages. However VPD has a high frequency of recurrences (15-62%), often irrespective for radicality of surgical excision. When association with underlying invasive adenocarcinoma or stromal invasion is histologically confirmed, vulvar surgical approach must be integrated with inguino-femoral lymphadenectomy. The role of chemotherapy and radiotherapy in the multimodal approach to extensive or recurring VPD is still controversial. Recurrences or progression of intraepithelal VPD are reported more than 10 years from first surgical resection so that long term follow-up is mandatory.

PMID: 11048477 [Indexed for MEDLINE]

63. Minerva Ginecol. 2000 May;52(5):197-201.

[Vulvar lesions caused by HPV].

[Article in Italian]

Micheletti L(1), Preti M, Bocci C, Bogliatto F, Condello V, Chieppa P.

Author information:

(1)Cattedra A del Dipartimento di Discipline Ginecologiche ed Ostetriche, Università degli Studi, Torino.

Human papillomavirus subclinical lesions are well known on the cervix and are identified by colposcopy after acetic acid staining. The transfer of this technique from the cervix to the vulva has led to the identification of areas of white epithelial changes which have been defined by similarity as vulvar subclinical HPV (VSHPV) lesions. A critical revision of the different clinical VSHPV lesions classifications, the vulvar diagnostic role of acetic acid staining, the natural history of HPV infection and the histological-biomolecular diagnostic techniques has the authors to the conclusions that the majority of the “so called” VSHPV lesions should not be considered a real disease. The presence of HPV-DNA in these subclinical lesions should be considered causal and not causal. To avoid overtreatments in women with proven HPV-DNA positivity without macroscopic clinical lesions, the authors recommend to abandon the acetic acid staining on the vulva and invite to consider the VSHPV lesions a faked diagnosis and not a clinical entity.

PMID: 11048476 [Indexed for MEDLINE]

64. BJOG. 2000 May;107(5):594-9. doi: 10.1111/j.1471-0528.2000.tb13298.x.

Inter-observer variation in histopathological diagnosis and grading of vulvar intraepithelial neoplasia: results of an European collaborative study.

Preti M(1), Mezzetti M, Robertson C, Sideri M.

Author information:

(1)Department of Obstetrics and Gynaecology, University of Turin, Italy.

OBJECTIVE: To evaluate the inter-observer variability of vulvar intraepithelial neoplasia diagnosis and grading system.

DESIGN: Prospective study.

SAMPLE: Histological sections of 66 vulvar biopsies.

METHODS: Six consultant pathologists working at different European institutions independently reviewed 66 vulvar biopsies. The following variables were investigated: specimen adequacy, gross categorisation into benign or neoplastic changes, presence of atypical cytological pattern, presence of neoplastic architectural pattern, grade of vulvar intraepithelial neoplasia, presence of histopathologic associated findings for human papillomavirus infection.

MAIN OUTCOME MEASURES: The degree of inter-observer variation for each histopathologic parameter was assessed by Kappa (kappa) statistics. The frequency and the degree of disagreement were calculated by a symmetrical agreement matrix showing the number paired classifications.

RESULTS: A good agreement (overall weighted kappa = 0.65, unweighted kappa = 0.46) was observed for grading vulvar intraepithelial neoplasia. Human papillomavirus infection associated findings and specimen adequacy were the variables with less inter-observer agreement (overall weighted kappa 0.26 and 0.22, respectively). Exact agreement between two pathologists for grade of vulvar intraepithelial neoplasia was observed in 63.6% of paired readings; the rate of paired agreement reached 73.9% considering vulvar intraepithelial neoplasia 2 and 3 as a single class. Conversely, only 5.0% of vulvar intraepithelial neoplasia 1 diagnoses were concordant in paired analysis.

CONCLUSIONS: Current terminology offers a reproducible tool in the hands of expert pathologists. While on the diagnosis of ‘high grade’ vulvar intraepithelial neoplasia (vulvar intraepithelial neoplasia 2 and 3) there is good agreement, the diagnostic category of vulvar intraepithelial neoplasia 1 is not reproducible.

DOI: 10.1111/j.1471-0528.2000.tb13298.x

PMID: 10826571 [Indexed for MEDLINE]

65. Cancer. 2000 Apr 15;88(8):1869-76.

Recurrent squamous cell carcinoma of the vulva: clinicopathologic determinants identifying low risk patients.

Preti M(1), Ronco G, Ghiringhello B, Micheletti L.

Author information:

(1)Department of Gynecology and Obstetrics, University of Turin, Turin, Italy. mario.preti@tin.it

BACKGROUND: The identification of prognostic factors in the recurrence of vulvar

squamous cell carcinoma is crucial for less invasive treatments.

METHODS: The authors studied 101 patients treated for primary invasive squamous cell carcinoma of the vulva. Selected pathologic variables were observed in a standardized manner during treatment, and their association with disease free survival was investigated using the Cox model. Independent prognostic factors were selected by a stepwise procedure. The absolute survival of patient groups determined on the basis of such factors was computed by the product limit method.

RESULTS: The median follow-up was 3.1 years (range, 56 days to 15.5 years). Recurrences developed in 33 patients. The independent recurrence predictors were as follows: International Federation of Gynecology and Obstetrics (FIGO) Stage IVA (vs. IB, II, or III) (risk ratio [RR]adjusted for other independent factors, 7.39), tumor multifocality (RR, 4.10), lymphovascular space involvement (LVSI) (RR, 2.96), the presence of associated vulvar intraepithelial neoplasia (VIN) Grade 2 or 3 (RR, 3.34), and the involvement of resection margins (RR, 4.88). By ignoring the FIGO stage and lymph node status, the independent predictors were then as follows: greatest tumor dimension < 2.5 cm, 2.5-4 cm (RR, 2.86), or > 4 cm (RR, 5.98); tumor multifocality (RR, 3.36); LVSI (RR, 4.19); the presence of VIN 2 or 3 (RR, 3.06); and the involvement of surgical margins (RR, 2.78). No recurrences were observed in 119 at-risk years among patients with unifocal tumors < 2.5 cm in greatest dimension, free surgical margins, no LVSI, and no associated VIN 2 or 3.

CONCLUSIONS: The presence of associated VIN 2 or 3 was revealed to be a previously unidentified independent prognostic factor for recurrence. Subjects at low risk of recurrence could be identified even without consideration of lymph node status.

PMID: 10760764 [Indexed for MEDLINE]

66. Cancer. 1998 Oct 1;83(7):1369-75.

A proposed glossary of terminology related to the surgical treatment of vulvar carcinoma.

Micheletti L(1), Preti M, Zola P, Zanotto Valentino MC, Bocci C, Bogliatto F.

Author information:

(1)Department of Gynecology and Obstetrics, University of Torino, Italy.

BACKGROUND: The authors’ objective was to provide a glossary of terminology related to the surgical treatment of invasive vulvar carcinoma. There is currently no consensus in the literature regarding the names of the surgical procedures used to treat this disease.

METHODS: A surgical glossary should be supported by clear definitions and acceptance of notions related to topographic anatomy that are specific to the surgical practice. A critical review of the classic, chiefly used Italian, French, German, and English textbooks of anatomy revealed some discrepancies and lack of uniformity in descriptions of vulvar and inguinal fascial structures and lymph nodes, which represent the principal landmarks of surgical treatment. In the proposed glossary, the descriptions of these anatomic landmarks integrate classic anatomic knowledge, data from recent gynecologic studies of inguinal anatomy, and the clinical experiences of the authors.

RESULTS: The glossary is composed of 16 surgical definitions, which are divided into 3 main sections of terminology describing the surgical treatment of the: 1) vulva, 2) inguinal lymph nodes, and 3) pelvic lymph nodes. The fundamental objective behind the glossary is to describe the area and the depth of the surgical procedure. Three determinants of the area (local, partial, and total) and three determinants of the depth of surgery (superficial, simple, and deep) were used to arrive at the fully articulated definitions in the glossary.

CONCLUSIONS: The authors are aware that the proposed glossary should not be considered a definitive one; however, it could serve as a good basis for further debate. The terms employed in the glossary are accompanied by anatomic and descriptive references to help avoid confusion and promote better understanding among gynecologic oncologists who are involved in the treatment of vulvar carcinoma.

PMID: 9762938 [Indexed for MEDLINE]

67. Minerva Ginecol. 1995 Jun;47(6):269-75.

[Terminology and classification problems in relation to vulvar pathology].

[Article in Italian]

Micheletti L(1), Nicolaci P, Barbero M, Zanotto Valentino MC, Preti M.

Author information:

(1)Cattedra A-Istituto di Ginecologia ed Ostetricia, Università degli Studi di Torino.

The aim of this paper is to update the physicians (gynecologists, dermatologists and pathologists) on the evolution of vulvar disease terminologies. In doing that the authors illustrate briefly the fundamental steps which led to present classifications of the International Society for the Study of Vulvar Disease (ISSVD). The classification of “non neoplastic epithelial disorders” together with that of “intraepithelial alterations” are illustrated and compared with the terminologies previously employed. The last ISSVD definition of “superficially invasive carcinoma” of the vulva is also presented and discussed. The authors concluded that even if all these ISSVD classifications represent an important effort for reaching a common language for a better international exchange of different experiences, nevertheless an improvement of these terminologies is still requested.

PMID: 7478097 [Indexed for MEDLINE]

68. J Reprod Med. 1994 Dec;39(12):961-3.

Psychological distress in women with nonneoplastic epithelial disorders of the vulva.

Preti M(1), Micheletti L, Barbero M, Piccioni V, Valentino MC, Nicolaci P, Borgno G.

Author information:

(1)Institute of Obstetrics and Gynecology, University of Torino, Italy.

The aim of this study was to evaluate psychological distress in 44 women with vulvar squamous cell hyperplasia and 21 with vulvar lichen sclerosus in order to examine the presence of psychological factors in these dermatologic disorders. Two psychometric tests were used to evaluate depressive status and various aspects of anger. No significant depressive status was diagnosed with the former test either in patients with vulvar squamous cell hyperplasia or in patients with vulvar lichen sclerosus. Patients with squamous cell hyperplasia had two components of anger (state and internal anger) that were significantly higher and three components (trait anger, exteriorization and control of anger) significantly lower than did the controls. In patients with lichen sclerosus all the components of anger were within the normal range. These findings suggest that psychological factors may be associated with vulvar conditions, such as squamous cell hyperplasia, and may have some therapeutic implications in cases resistant to standard treatment.

PMID: 7884753 [Indexed for MEDLINE]

69. J Reprod Med. 1994 Dec;39(12):949-52.

Membranous hypertrophy of the posterior fourchette as a cause of dyspareunia and vulvodynia.

Barbero M(1), Micheletti L, Valentino MC, Preti M, Nicolaci P, Ghiringhello B, Borgno G.

Author information:

(1)Institute of Gynaecology and Obstetrics, University of Torino, Italy.

Twenty-one women were treated surgically for entry dyspareunia and vulvodynia. The ages of the patients ranged from 18 to 39 years (mean, 24.5). Physical examination showed the presence of membranous hypertrophy of the posterior fourchette with consequent stricture of the vaginal introitus in all the patients. Eighty percent of the patients had erythema and tenderness of the vestibule, particularly in the posterior part. The histologic findings were somewhat enigmatic and quite unimpressive, frequently suggestive of chronic nonspecific inflammation; in only two cases were histologic changes suggestive of human papillomavirus infection observed. All the patients underwent excision of the posterior part of the vestibule with vaginal advancement under general anesthesia. Follow-up showed elimination of the symptoms in 19 patients and an improvement in the symptoms in the remaining 2.

PMID: 7884750 [Indexed for MEDLINE]

70. Minerva Ginecol. 1994 Apr;46(4):195-204.

[Current knowledge about the natural history of intraepithelial neoplasms of the vagina].

[Article in Italian]

Micheletti L(1), Zanotto Valentino MC, Barbero M, Preti M, Nicolaci P, Canni M.

Author information:

(1)Istituto di Ginecologia ed Ostetricia, Cattedra A, Università degli Studi di Torino.

The data on the natural history of vaginal intraepithelial neoplasia (VaIN) available in the literature are scarce and incomplete. As a matter of fact the majority of the Authors report series with a small number of cases, which are predominantly represented by VaIN III and usually already treated. Nevertheless from the review of the literature it seems that VaIN, particularly those of low grade (I-II), tend to show a high rate of spontaneous regression. The lesions are frequently multifocal, associated with papilloma virus (HPV) infection and arising in young women. On the contrary, the VaIN showing a more aggressive behaviour are usually represented by single lesions, arising in older women. Those patients are also frequently immunosuppressed, with a history of preceding genital neoplasia and a previous exposure to radiation and/or chemotherapy.

PMID: 8065594 [Indexed for MEDLINE]

71. Eur J Gynaecol Oncol. 1994;15(1):70-4.

Vulvar intraepithelial neoplasia of low grade: a challenging diagnosis.

Micheletti L(1), Barbero M, Preti M, Zanotto Valentino MC, Chiringhello B, Pippione M.

Author information:

(1)Institute of Gynecology and Obstetrics, Chair University of Turin, Italy.

The authors reviewed 21 cases of “mild vulvar atypia” diagnosed from 1981 to 1990. The first 16 cases were diagnosed as hyperplastic dystrophy with mild atypia according to the 1976 ISSVD Classification of Vulvar Disease, while the last five cases were diagnosed as vulvar intraepithelial neoplasia grade I (VIN I). The review of the specimens was made by the same pathologist who gave the initial diagnosis and by a dermatopathologist unaware of the initial diagnosis. Both reviewers used the 1986 and 1989 ISSVD terminologies. The presence of “mild atypia” was confirmed in only four of the 21 specimens, that is in 19% of the cases, and two of them were found in the context of patients suffering from a lichen planus. These findings show that the diagnosis of mild atypia in vulvar tissues is a challenge and that mild vulvar atypia cannot be automatically considered a VIN I.

PMID: 8206076 [Indexed for MEDLINE]

72. J Reprod Med. 1993 Feb;38(2):108-12.

Biologic behavior of vulvar intraepithelial neoplasia. Histologic and clinical parameters.

Barbero M(1), Micheletti L, Preti M, Valentino MC, Nicolaci P, Canní M, Ghiringhello B, Borgno G.

Author information:

(1)Institute of Gynecology and Obstetrics, University of Turin, Italy.

The aim of this study was to evaluate the role by which different factors, such as human papillomavirus (HPV) infection, age, dystrophic alterations, focal nature and size of the lesion, influence the biologic behavior of vulvar intraepithelial neoplasia (VIN). Sixty-nine cases of VIN were investigated (28 VIN 1, 9 VIN 2, 32 VIN 3). Follow-up was possible in 58 cases, with a mean of 31 months; no treatment was given to 3 patients, while 55 were treated either medically or surgically. Eighty-four percent of the patients were cured, recurrences were found in 11%, and 5% of the patients showed progression of the disease to carcinoma. The ratio between medical and surgical treatment was the same among the cured, recurred and progressed groups of patients. No differences with regard to focal nature of the lesion, presence of HPV infection or dystrophic alterations were observed between the three groups of patients. Only the mean age was higher in patients who showed progression of the lesion to carcinoma.

PMID: 8383203 [Indexed for MEDLINE]

73. J Reprod Med. 1993 Jan;38(1):28-32.

Histologic parameters of vulvar invasive carcinoma and lymph node metastases.

Preti M(1), Micheletti L, Barbero M, Ghiringhello B, Valentino MC, Nicolaci P, Canni M, Borgno G, Segnan N, Ronco G.

Author information:

(1)Institute of Gynaecology and Obstetrics, University of Torino, Italy.

We evaluated seven histologic parameters (tumor diameter, histologic grading, depth of stromal invasion, vascular invasion, pattern of invasion, lymphoplasmocytic infiltration and amount of necrosis) of 50 cases of vulvar invasive carcinoma to assess their correlation with groin lymph node metastases. Of 50 patients, 25 had groin lymph node metastases. No lymph node metastasis was found in four cases with depth of invasion < or = 2.0 mm. Among the 31 patients with vascular invasion, 23 (74%) had positive nodes, whereas lymph nodes were metastatic only in two of the 19 patients (10%) without vascular invasion. At univariate analysis, performed with Fisher’s exact method, all the parameters considered, except pattern of invasion and amount of necrosis, were significantly associated (P < .05) with lymph node metastases. However, after adjustment by multiple logistic regression for the variables statistically significant at univariate level, only the presence of vascular invasion was significantly associated with nodal involvement and tumor diameter was borderline, whereas the effect of the other variables was almost completely explained by confounding.

PMID: 8441127 [Indexed for MEDLINE]

74. Minerva Ginecol. 1992 Jun;44(6):329-34.

[Intra-lesion administration of beta-interferon in the treatment of CIN associated with HPV infection].

[Article in Italian]

Micheletti L(1), Barbero M, Preti M, Zanotto Valentino MC, Nicolaci P, Corbella L, Borgno G.

Author information:

(1)Istituto di Ginecologia ed Ostetricia, Università degli Studi di Torino.

Thirty-two women with histologically confirmed cervical intraepithelial neoplasia (CIN) associated with human papillomavirus (HPV) infection were treated with intralesional beta-interferon. At 12 months from the end of the treatment, 60% of the patients showed complete regression, histologically assessed, of CIN. Considering separately the different CIN grades, the regression for CIN I was 71%, 64% for CIN II and 45% for CIN III. Side-effects were rather frequent (84%) but they did not require discontinuation of the treatment. On the basis of these data the Authors believe that intralesional beta-interferon, in selected cases, can play a role, as a conservative modality, among the different techniques of CIN therapy.

PMID: 1321960 [Indexed for MEDLINE]

75. J Reprod Med. 1990 Dec;35(12):1130-3.

Deep femoral lymphadenectomy with preservation of the fascia lata. Preliminary report on 42 invasive vulvar carcinomas.

Micheletti L(1), Borgno G, Barbero M, Preti M, Cavanna L, Nicolaci P, Benedetto C, Ghiringhello B, Bocci A.

Author information:

(1)Institute of Gynecology and Obstetrics, University of Turin, Italy.

Forty-two patients with primary invasive vulvar carcinoma were treated with radical vulvectomy and deep femoral lymphadenectomy with preservation of the fascia lata and cribriform fascia. The rationale for using this technique was based on anatomic knowledge of the topographic distribution of groin lymph nodes, which was confirmed by the study of 50 cadavers. The preliminary data show that the number of superficial and deep femoral lymph nodes removed from the 42 patients (mean number of nodes, 20; range, 8-32) was similar to the number reported in anatomy books. In addition, the five-year actuarial survival rate, 70%, was comparable to that in the literature. These preliminary results suggest that the surgical technique used in this study is as radical an oncologic procedure as Way’s classic groin lymphadenectomy, which consists of removing the fascia lata and cribriform fascia.

PMID: 2283630 [Indexed for MEDLINE]

76. J Reprod Med. 1990 Dec;35(12):1127-9.

Topographic distribution of groin lymph nodes. A study of 50 female cadavers.

Borgno G(1), Micheletti L, Barbero M, Cavanna L, Preti M, Valentino MC, Ghiringhello B, Bocci A.

Author information:

(1)Institute of Gynecology and Obstetrics, University of Turin, Italy.

There is a discrepancy between anatomy textbooks’ description of groin node position and Way’s technique of lymphadenectomy. On the one hand, anatomic studies have demonstrated that the deep femoral nodes are on the medial side of the femoral vein, lying on the deep portion of the fascia lata, and can be seen easily through the opening of the fossa ovalis. On the other hand, the standard technique of deep femoral lymphadenectomy consists of removing the fat lying lateral to the femoral artery through the incision and detachment of the fascia lata from the sartorius to adductor longus muscle. With the aim of demonstrating that a correct deep femoral lymphadenectomy does not require removal of the fascia lata, we dissected Scarpa’s triangles in 50 female cadavers. The examination of 100 specimens demonstrated that the deep femoral nodes are always situated within the opening of the fossa ovalis, and no lymph nodes are distal to the lower margin of the fossa ovalis, under the fascia cribrosa. These findings suggest that deep femoral lymphadenectomy can be performed without removing the fascia lata.

PMID: 2283629 [Indexed for MEDLINE]

77. J Reprod Med. 1990 Nov;35(11):1023-8.

Vulvar intraepithelial neoplasia. A clinicopathologic study of 60 cases.

Barbero M(1), Micheletti L, Preti M, Cavanna L, Boselli F, Garuti G, Valentino MC, Nicolaci P, Ghiringhello B, Borgno G.

Author information:

(1)Institute of Gynecology and Obstetrics, Chair A, University of Turin, Italy.

Sixty cases of vulvar intraepithelial neoplasia (VIN) were analyzed clinicopathologically (24 VIN I, 9 VIN II, 27 VIN III). The ages of the patients ranged from 21 to 83 years (mean, 53.7). Colposcopic examinations showed the presence of white areas in 29 cases, red areas in 9, acetowhite areas in 6 and other alterations in 13. One-third of the lesions were multifocal. Pruritus and burning were present in 65% of the cases. Fifty-one percent of the cases showed histologic changes suggestive of human papillomavirus (HPV) infection; the mean age of those patients was significantly lower than that of patients without HPV infection. In 15 cases of VIN, HPV DNA testing was performed with Southern blot hybridization; in three (20%) of those specimens HPV 16 episomal DNA was identified. Epithelial alterations surrounding the areas of VIN were found in 24 cases (40%)-23 squamous cellular hyperplasias and 1 lichen sclerosus. Different types of treatment were performed according to the different grades of VIN: medical therapy, diathermocoagulation, local excision, hemivulvectomy and total vulvectomy. Follow-up was possible in 52 cases, with a mean of 33 months (range, 3-98). Two cases of VIN I showed progression of disease over 12-24 months.

PMID: 2177508 [Indexed for MEDLINE]

78. Minerva Ginecol. 1988 Oct;40(10):603-6.

[Cervical intraepithelial neoplasia caused by human papillomavirus infection. Cytomorphologic, colposcopic and immunohistochemical correlations].

[Article in Italian]

Preti M, Micheletti L, Barbero M, Cavanna L, Ghiringhello B, Borgno G.

PMID: 2851756 [Indexed for MEDLINE]

79. Minerva Ginecol. 1988 Dec;40(12):743-7.

[Condylomata acuminata and vulvar intraepithelial neoplasms (VIN)].

[Article in Italian]

Barbero M, Micheletti L, Cavanna L, Preti M, Zanotto Valentino MC, Ghiringhello B, Borgno G.

PMID: 2854229 [Indexed for MEDLINE]

80. J Reprod Med. 1988 Jun;33(6):555-8.

Vulvar dystrophies in young and premenopausal women.

Barbero M(1), Micheletti L, Borgno G, Cavanna L, Preti M, Ghiringhello B.

Author information:

(1)Institute of Gynecology and Obstetrics, University of Turin, Italy.

Eighty-six cases of vulvar dystrophy in young and premenopausal women (age range, 6-53 years) were studied clinically and histopathologically. The most frequent symptom was pruritus associated with burning. Clinical examination showed the presence of white areas in 73% of the patients, red areas in 9% and other signs (such as melanosis) in 18%. Hyperplastic dystrophy was the most frequent type of dystrophy in these patients and was observed in 63% of cases. Cellular atypia was observed in 9.8% of the cases and was found almost exclusively in hyperplastic dystrophy. Epithelial changes suggestive of human papillomavirus infection were found in 4 of the 86 cases of dystrophy, and they were observed only in atypical dystrophies.

PMID: 3404518 [Indexed for MEDLINE]

81. J Reprod Med. 1988 Jun;33(6):539-41.

Cellular atypia in vulvar dystrophies.

Micheletti L(1), Borgno G, Barbero M, Preti M, Cavanna L, Benedetto C, Ghiringhello B.

Author information:

(1)Institute of Gynecology and Obstetrics, University of Turin, Italy.

We studied the frequency and distribution of cellular atypia in 448 cases of vulvar dystrophy. The total frequency was 9.4%. Atypia was found almost exclusively in hyperplastic areas. Epithelial changes suggestive of human papillomavirus infection were found in 14.2% of the atypical dystrophies. During the follow-up of 78 patients with typical dystrophy, mild atypia developed in three cases, but with the continuation of medical treatment it disappeared in two cases. Eleven cases of atypical dystrophy were followed for 3-48 months; three patients with severe atypia underwent surgical treatment, and eight with mild atypia underwent medical treatment. Among the last patients, six showed regression and two, progression of the atypia.

PMID: 3404515 [Indexed for MEDLINE]

82. J Reprod Med. 1988 Jun;33(6):500-2.

Epithelial alterations adjacent to 111 vulvar carcinomas.

Borgno G(1), Micheletti L, Barbero M, Preti M, Cavanna L, Ghiringhello B.

Author information:

(1)Institute of Gynecology and Obstetrics, University of Turin, Italy.

Material from 111 invasive primary vulvar carcinomas was reviewed in order to study the histopathologic changes adjacent to the neoplasia. The histopathologic characteristics of the adjacent tissue were divided into categories. Dystrophic lesions were adjacent to invasive cancer in 57.6% of the cases, carcinoma in situ (CIS) in 21.6% and epithelial changes suggestive of human papillomavirus infection in 18.9%. A spectrum of epithelial changes, ranging from hyperplastic dystrophy without atypia to CIS, was found adjacent to nine cases of invasive carcinoma (8.1%). In 40.5% of the vulvar carcinomas there were no specific alterations surrounding the neoplasia. These data show that dystrophies and CIS were adjacent to invasive carcinomas in nearly 60% and 20% of cases, respectively.

PMID: 2841458 [Indexed for MEDLINE]