Skip to main content
SpringerLink
Log in

Risk Factors and Classification of Vulvar Intraepithelial Lesions

  • Chapter
  • First Online:
Preventive Oncology for the Gynecologist

  • 476 Accesses

Abstract

The history of vulvar intraepithelial neoplasia (VIN) dates back to more than a century.

Over the last few years, vulvar intraepithelial lesions have shown an increasing trend with a propensity of presenting at a younger age (Judson et al., Obstet Gynecol 107:1018–1022, 2006). However, the incidence of vulvar squamous cell carcinoma (VSCC) does not show a proportionate rise (Bodelon et al., Cancer Causes Control 20(9):1779–1782, 2009). The terminology and classification of vulvar intraepithelial lesions have been quite confusing and revised multiple times by the World Health Organization (WHO) and International Society for the Study of Vulvovaginal Disease (ISSVD) over the years. Two distinct oncogenic pathways have been described: human papillomavirus (HPV)-related and non-HPV-related. Low-risk HPV 6 and 11 are associated with low-grade squamous intraepithelial lesions (LSIL), whereas high-risk HPV (16, 18, 31, 33) are associated with high-grade squamous intraepithelial lesions (HSIL). Chronic dermatologic conditions such as lichen sclerosus are associated with differentiated VIN (dVIN), which carries a higher risk of progression to carcinoma compared to HPV-related lesions.

The common risk factors associated with VIN and progression to cancer are age, immunosuppression, smoking, sexual behaviour and chronic dermatologic conditions like lichen sclerosus, and these will be dealt in detail in this chapter.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Judson PL, Habermann EB, Baxter NN, Durham SB, Virnig BA. Trends in the incidence of invasive and in situ vulvar carcinoma. Obstet Gynecol. 2006;107:1018–22.

    Article  Google Scholar 

  2. Bodelon C, Madeleine MM, Voigt LF, Weiss NS. Is the incidence of invasive vulvar cancer increasing in the United States? Cancer Causes Control. 2009;20(9):1779–82.

    Article  Google Scholar 

  3. SEER Cancer Stat Facts 2017: Vulvar Cancer. National Cancer Institute. Bethesda, MD. http://seer.cancer.gov/statfacts/html/vulva.html.

  4. De Yust H, Clifford GM, Nascimento MC, Madeleine MM, Franceschi S. Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis. Int J Cancer. 2009;124(7):1626–36. https://doi.org/10.1002/ijc.24116.

    Article  CAS  Google Scholar 

  5. Trimble CL, Hildesheim A, Brinton LA, Shah KV, Kurman RJ. Heterogeneous etiology of squamous carcinoma of the vulva. Obstet Gynecol. 1996;87(1):59–64.

    Article  CAS  Google Scholar 

  6. Preti M, Scurry J, Marchitelli CE, Micheletti L. Vulvar intraepithelial neoplasia. Best Pract Res Clin Obstet Gynaecol. 2014;28:1051–62.

    Article  Google Scholar 

  7. Bornstein J, Bogliatto F, Haefner HK, Stockdale CK, Preti M, Bohl TG, et al. The 2015 International Society for the Study of Vulvovaginal Disease (ISSVD) terminology of vulvar squamous intraepithelial lesions. J Low Genit Tract Dis. 2016;20:11–4.

    Article  Google Scholar 

  8. Bowen JT. Centennial paper. May 1912 (J Cutan Dis Syph 1912;30:241-255). Precancerous dermatoses: a study of two cases of chronic atypical epithelial proliferation. Arch Dermatol. 1983;119:243–60.

    Article  CAS  Google Scholar 

  9. Hudelo ML, Cailliau O. Dyskeratose erythroplasiforme de la muqueuse vulvaire. Bull Soc Franc Dermatol Syph. 1922;29:139–42.

    Google Scholar 

  10. Knight RVD. Bowen’s disease of the vulva. Am J Obstet Gynecol. 1943;undefined:514–24.

    Article  Google Scholar 

  11. Woodruff JD, Hildebrandt EE. Carcinoma in situ of the vulva. Obstet Gynecol. 1958;12(4):414–24.

    CAS  PubMed  Google Scholar 

  12. Abell MR, Gosling JR. Intraepithelial and infiltrative carcinoma of vulva: Bowen’s type. Cancer. 1961;14:318–29.

    Article  CAS  Google Scholar 

  13. Preti M, Van Seters M, Sideri M, Van Beurden M. Squamous vulvar intraepithelial neoplasia. Clin Obstet Gynecol. 2005;48:845–61.

    Article  Google Scholar 

  14. Berger BW, Hori Y. Multicentric Bowen’s disease of the genitalia: spontaneous regression of lesions. Arch Dermatol. 1978;114:1698–9.

    Article  CAS  Google Scholar 

  15. Friedrich EG. Reversible vulvar atypia. A case report. Obstet Gynecol. 1972;39:173–81.

    PubMed  Google Scholar 

  16. Richart RM. Natural history of cervical intraepithelial neoplasia. Clin Obstet Gynecol. 1967;10:748–84.

    Article  Google Scholar 

  17. Wade TR, Kopf AW, Ackerman AB. Bowenoid papulosis of the genitalia. Arch Dermatol. 1979;115:306–8.

    Article  CAS  Google Scholar 

  18. Kaufman R, DiPaola G, Friedrich E, et al. New nomenclature for vulvar disease. Obstet Gynecol. 1976;47:122–4.

    Google Scholar 

  19. Crum CP, Fu YS, Levine RU, Richart RM, Townsend DE, Fenoglio CM. Intraepithelial squamous lesions of the vulva: biologic and histologic criteria for the distinction of condylomas from vulvar intraepithelial neoplasia. Am J Obstet Gynecol. 1982;144:77–83.

    Article  CAS  Google Scholar 

  20. Wilkinson EJ, Kneale B, Lynch PJ. Report of the ISSVD terminology committee. Reprod Med. 1986;31:973–4.

    Google Scholar 

  21. Sideri M, Jones RW, Wilkinson EJ, Preti M, Heller DS, Scurry J, et al. Squamous vulvar intraepithelial neoplasia: 2004 modified terminology, ISSVD Vulvar Oncology Subcommittee. J Reprod Med. 2005;50:807–10.

    PubMed  Google Scholar 

  22. Scurry J, Wilkinson EJ. Review of terminology of precursors of vulvar squamous cell carcinoma. J Low Genit Tract Dis. 2006;10:161–9.

    Article  Google Scholar 

  23. Medeiros F, Nascimento AF, Crum CP. Early vulvar squamous neoplasia: advances in classification, diagnosis, and differential diagnosis. Adv Anat Pathol. 2005;12:20–6.

    Article  Google Scholar 

  24. Darragh TM, Colgan TJ, Thomas Cox J, Heller DS, Henry MR, Luff RD, McCalmont T, Members of the LAST Project Work Groups, et al. The lower anogenital squamous terminology standardization project for HPV associated lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Int J Gynecol Pathol. 2013;32(1):76–115.

    Article  Google Scholar 

  25. Kurman RJ, Carcangiu ML, Herrington CS, editors. WHO classification of tumours of female reproductive organs. 4th ed. Lyon: International Agency for Research on Cancer; 2014. p. 229–53.

    Google Scholar 

  26. Van de Nieuwenhof HP, van der Avoort IA, de Hullu JA. Review of squamous premalignant vulvar lesions. Crit Rev Oncol Hematol. 2008;68:131–56.

    Article  Google Scholar 

  27. Saraiya M, Watson M, Wu X, King JB, Chen VW, Smith JS, et al. Incidence of in situ and invasive vulvar cancer in the US,1998 - 2003. Cancer. 2008;113:2865–72.

    Article  Google Scholar 

  28. Committee opinion no. 675 summary: management of vulvar intraepithelial neoplasia. Obstet Gynecol 2016;128:937–8.

    Google Scholar 

  29. Eva LJ, Ganesan R, Chan KK, Honest H, Luesley DM. Differentiated-type vulval intraepithelial neoplasia has a high-risk association with vulval squamous cell carcinoma. Int J Gynecol Cancer. 2009;19:741–4.

    Article  Google Scholar 

  30. Preti M, Bucchi L, Ghiringhello B, Privitera S, Frau V, Corvetto E, et al. Risk factors for unrecognized invasive carcinoma in patients with vulvar high-grade squamous intraepithelial lesion at vulvoscopy-directed biopsy. J Gynecol Oncol. 2017;28(4):e27. https://doi.org/10.3802/jgo.2017.28.e27.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Chiesa-Vottero A, Dvoretsky PM, Hart WR. Histopathologic study of thin vulvar squamous cell carcinomas and associated cutaneous lesions: a correlative study of 48 tumors in 44 patients with analysis of adjacent vulvar intraepithelial neoplasia types and lichen sclerosus. Am J Surg Pathol. 2006;30:310–8.

    Article  Google Scholar 

  32. Van de Nieuwenhof HP, Massuger LF, van der Avoort IA, Bekkers RL, Casparie M, Abma W, et al. Vulvar squamous cell carcinoma development after diagnosis of VIN increases with age. Eur J Cancer. 2009;45:851–6.

    Article  Google Scholar 

  33. Jones RW, Rowan DM, Stewart AW. Vulvar intraepithelial neoplasia: aspects of the natural history and outcome in 405 women. Obstet Gynecol. 2005;106:319–1326.

    Article  Google Scholar 

  34. Zur Hausen H. Papillomaviruses in the causation of human cancers – a brief historical account. Virology. 2009;384:260–5.

    Article  CAS  Google Scholar 

  35. Zachow KR, Ostrow RS, Bender M, Watts S, Okagaki T, Pass F, et al. Detection of human papillomavirus DNA in anogenital neoplasias. Nature. 1982;300:771–3.

    Article  CAS  Google Scholar 

  36. Haefner HK, Tate JE, McLachlin CM, Crum CP. Vulvar intraepithelial neoplasia: age, morphological phenotype, papillomavirus DNA, and coexisting invasive carcinoma. Hum Pathol. 1995;26:147–54.

    Article  CAS  Google Scholar 

  37. Park JS, Jones RW, McLean MR, Currie JL, Woodruff JD, Shah KV, et al. Possible etiologic heterogeneity of vulvar intraepithelial neoplasia. A correlation of pathologic characteristics with human papillomavirus detection by in situ hybridization and polymerase chain reaction. Cancer. 1991;67:1599–607.

    Article  CAS  Google Scholar 

  38. Del Pino M, Rodriguez-Carunchio L, Ordi J. Pathways of vulvar intraepithelial neoplasia and squamous cell carcinoma. Histopathology. 2013;62:161–75.

    Article  Google Scholar 

  39. Léonard B, Kridelka F, Delbecque K, Goffin F, Demoulin S, Doyen J, et al. A clinical and pathological overview of vulvar condyloma acuminatum, intraepithelial neoplasia, and squamous cell carcinoma. Biomed Res Int. 2014;2014:480573.

    Article  Google Scholar 

  40. De Sanjosé S, Alemany L, Ordi J, Tous S, Alejo M, Bigby SM, et al. Worldwide human papillomavirus genotype attribution in over 2000 cases of intraepithelial and invasive lesions of the vulva. Eur J Cancer. 1990;49:3450–61.

    Article  Google Scholar 

  41. Santos M, Landolfi S, Olivella A, Lloveras B, Klaustermeier J, Suárez H, et al. p16 overexpression identifies HPV-positive vulvar squamous cell carcinomas. Am J Surg Pathol. 2006;30:1347–56.

    Article  Google Scholar 

  42. Committee opinion no. 675 summary: management of vulvar intraepithelial neoplasia. Obstet Gynecol. 2016;128(4):937–8. https://doi.org/10.1097/AOG.0000000000001704.

  43. Wilkinson EJ, Cook JC, Friedrich EG Jr, Massey J. Vulvar intraepithelial neoplasia: association with cigarette smoking. J Gynecol Surg. 2009;4(3):153–9. https://doi.org/10.1089/gyn.1988.4.153.

    Article  Google Scholar 

  44. Khan AM, Freeman-Wang T, Pisal N, Singer A. Smoking and multicentric vulval intraepithelial neoplasia. J Obstet Gynaecol. 2009;29(2):123–5. https://doi.org/10.1080/01443610802668938.

    Article  CAS  PubMed  Google Scholar 

  45. MacLean AB, Lynn KL, Bailey RR, Swainson CP, Walker RJ. Colposcopic assessment of the lower genital tract in female renal transplant recipients. Clin Nephrol. 1986;26:45–7.

    CAS  PubMed  Google Scholar 

  46. Wallbillich JJ, Rhodes HE, Milbourne AM, Munsell MF, Frumovitz M, Brown J, et al. Vulvar intraepithelial neoplasia (VIN2/3): comparing clinical outcomes and evaluating risk factors for recurrence. Gynecol Oncol. 2012;127(2):312–5. https://doi.org/10.1016/j.ygyno.2012.07.118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Ferenczy C, Coutlée F, Franco E, Hankins C. Human papilloma virus and HIV confection and the risk of neoplasias of the lower genital tract: a review of recent developments. CMAJ. 2003;169:431–4.

    PubMed  PubMed Central  Google Scholar 

  48. Bradbury M, Cabrera S, García-Jiménez A, Franco-Camps S, Sánchez-Iglesias JL, Díaz-Feijoo B, et al. Vulvar intraepithelial neoplasia: clinical presentation, management and outcomes in women infected with HIV. AIDS. 2016;30(6):859–68. https://doi.org/10.1097/QAD.0000000000000984.

    Article  CAS  PubMed  Google Scholar 

  49. Hart WR, Norris HJ, Helwig EB. Relation of lichen sclerosus et atrophicus of the vulva to development of carcinoma. Obstet Gynecol. 1975;45:369–77.

    CAS  PubMed  Google Scholar 

  50. Lee A, Bradford J, Fischer G. Long-term management of adult vulvar lichen sclerosus: a prospective cohort study of 507 women. JAMA Dermatol. 2015;151:1061–7.

    Article  Google Scholar 

  51. Weyers W. Hypertrophic lichen sclerosus with dyskeratosis and parakeratosis—a common presentation of vulvar lichen sclerosus not associated with a significant risk of malignancy. Am J Dermatopathol. 2013;35:713–21.

    Article  Google Scholar 

  52. Bleeker MC, Visser PJ, Overbeek LI, van Beurden M, Berkhof J. Lichen sclerosus: incidence and risk of vulvar squamous cell carcinoma. Epidemiol Biomarkers Prev. 2016;25(8):1224–30. https://doi.org/10.1158/1055-9965.EPI-16-0019.

    Article  CAS  Google Scholar 

  53. Bigby SM, Eva LJ, Fong KL, Jones RW. The natural history of vulvar intraepithelial neoplasia, differentiated type: evidence for progression and diagnostic challenges. Gynecol Pathol. 2016;35(6):574–84.

    Article  CAS  Google Scholar 

  54. Simpson RC, Littlewood SM, Cooper SM, Cruickshank ME, Green CM, Derrick E, et al. Real-life experience of managing vulval erosive lichen planus: a case-based review and U.K. multicentre case note audit. Br J Dermatol. 2012;167:85e91.

    Article  Google Scholar 

  55. Crum CP, Herrington CS, McCluggage WG, et al. Tumours of the vulva: epithelial tumours. In: Kurman JR, Carcangiu ML, Herrington CS, Young RH, editors. World Health Organization classification of tumours of the female reproductive organs. 4th ed. Lyon: IARC Press; 2014. p. 232–41.

    Google Scholar 

  56. Kingston NJ, Jones RW, Baranyai J. Recurrent primary vulvovaginal malignant melanoma arising in melanoma in situ—the natural history of lesions followed for 23 years. Int J Gynecol Cancer. 2004;14:628–32.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gynaecological Oncology, St. John’s Medical College and Hospital, Bangalore, Karnataka, India

    Kiran Abhijit Kulkarni, Geeta Acharya & G. Sumangala

Authors
  1. Kiran Abhijit Kulkarni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Geeta Acharya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Sumangala
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Obstetrics and Gynecology, Babu Jagjivan Ram Memorial Hospital, New Delhi, India

    Sumita Mehta

  2. Department of Obstetrics and Gynecology, University College of Medical Sciences and Guru Teg Bahadur Hospital, New Delhi, India

    Anshuja Singla

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kulkarni, K.A., Acharya, G., Sumangala, G. (2019). Risk Factors and Classification of Vulvar Intraepithelial Lesions. In: Mehta, S., Singla, A. (eds) Preventive Oncology for the Gynecologist. Springer, Singapore. https://doi.org/10.1007/978-981-13-3438-2_21

Download citation

  • DOI: https://doi.org/10.1007/978-981-13-3438-2_21

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-13-3437-5

  • Online ISBN: 978-981-13-3438-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation