Vulvar Disease pp 385-391 | Cite as

Nonsurgical Treatment of Preneoplastic Vulvar Conditions

  • Mario Preti
  • Gianluigi Radici
  • Leonardo Micheletti


Five to eighteen percent of biopsies of vulvar intraepithelial lesions can have unsuspected stromal invasion on the final specimen. Therefore, a meticulous examination is important before applying a nonsurgical treatment, such as imiquimod, cidofovir, photodynamic therapy, or therapeutic HPV vaccination.


  1. 1.
    Bornstein J, Bogliatto F, Haefner HK, et al. The 2015 International Society for the Study of Vulvovaginal Disease (ISSVD) terminology of vulvar squamous intraepithelial lesions. Obstet Gynecol. 2016;127:264–8.CrossRefGoogle Scholar
  2. 2.
    Preti M, Scurry J, Marchitelli CE, et al. Vulvar intraepithelial neoplasia. Best Pract Res Clin Obstet Gynaecol. 2014;28:1051–62.CrossRefGoogle Scholar
  3. 3.
    Preti M, Bucchi L, Ghiringhello B, 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:e27.CrossRefGoogle Scholar
  4. 4.
    Van de Nieuwenhof HP, Massuger LF, van der Avoort IA, et al. Vulvar squamous cell carcinoma development after diagnosis of VIN increases with age. Eur J Cancer. 2009;45:851–6.CrossRefGoogle Scholar
  5. 5.
    Jones RW, Rowan DM, Stewart AW. Vulvar intraepithelial neoplasia: aspects of the natural history and outcome in 405 women. Obstet Gynecol. 2005;106:1319e26.CrossRefGoogle Scholar
  6. 6.
    Lawrie TA, Nordin A, Chakrabarti M, et al. Medical and surgical interventions for the treatment of usual-type vulval intraepithelial neoplasia. Cochrane Database Syst Rev. 2016;1:5.Google Scholar
  7. 7.
    American College of Obstetrics and Gynecologists Committee. Opinion summary number 675: management of vulvar intraepithelial neoplasia. Obstet Gynecol. 2016;128:937–8.CrossRefGoogle Scholar
  8. 8.
    van Seters M, van Beurden M, ten Kate FJ, et al. Treatment of vulvar intraepithelial neoplasia with topical imiquimod. N Engl J Med. 2008;358:1465e73.Google Scholar
  9. 9.
    Terlou A, van Seters M, Kleinjan A, et al. Imiquimod-induced clearance of HPV is associated with normalization of immune cell counts in usual type vulvar intraepithelial neoplasia. Int J Cancer. 2010;127:2831–40.CrossRefGoogle Scholar
  10. 10.
    Terlou A, van Seters M, Ewing PC, et al. Treatment of vulvar intraepithelial neoplasia with topical imiquimod: seven years median follow-up of a randomized clinical trial. Gynecol Oncol. 2011;121:157–62.CrossRefGoogle Scholar
  11. 11.
    Stern PL, van der Burg SH, Hampson IN, et al. Therapy of human papillomavirus-related disease. Vaccine. 2012;20(30 Suppl 5):F71–82.CrossRefGoogle Scholar
  12. 12.
    Tristram A, Fiander A. Clinical responses to cidofovir applied topically to women with high grade vulval intraepithelial neoplasia. Gynecol Oncol. 2005;99:652–5.CrossRefGoogle Scholar
  13. 13.
    Jones SEF, Hibbitts S, Hurt CN, et al. Human papillomavirus DNA methylation predicts response to treatment using cidofovir and imiquimod in vulval intraepithelial neoplasia 3. Clin Cancer Res. 2017;23:5460–8.CrossRefGoogle Scholar
  14. 14.
    Tristram A, Hurt CN, Madden T, et al. Activity, safety, and feasibility of cidofovir and imiquimod for treatment of vulval intraepithelial neoplasia (RT3VIN): a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2014;15:1361–8.CrossRefGoogle Scholar
  15. 15.
    Hurt CN, Jones SEF, Madden TA, et al. Recurrence of vulval intraepithelial neoplasia following treatment with cidofovir or imiquimod: results from a multi-centre, randomised, phase II trial (RT3VIN). BJOG. 2018.
  16. 16.
    Dougherty TJ, Gomer CJ, Henderson BW, Jori G, Kessel D, Korbelik M, Moan J, Peng Q. Photodynamic therapy. J Natl Cancer Inst. 1998;90:889–905.CrossRefGoogle Scholar
  17. 17.
    Abdel-Hady ES, Martin-Hirsch P, Duggan-Keen M, et al. Immunological and viral factors associated with the response of vulval intraepithelial neoplasia to photodynamic therapy. Cancer Res. 2001;61:192–6.PubMedGoogle Scholar
  18. 18.
    Hillemanns P, Untch M, Dannecker C, et al. Photodynamic therapy of vulvar intraepithelial neoplasia using 5-aminolevulinic acid. Int J Cancer. 2000;85:649–53.CrossRefGoogle Scholar
  19. 19.
    Fehr MK, Hornung R, Degen A, et al. Photodynamic therapy of vulvar and vaginal condyloma and intraepithelial neoplasia using topically applied 5-aminolevulinic acid. Lasers Surg Med. 2002;30:273–9.CrossRefGoogle Scholar
  20. 20.
    Hillemanns P, Wang X, Staehle S, et al. Evaluation of different treatment modalities for vulvar intraepithelial neoplasia (VIN): CO(2) laser vaporization, photodynamic therapy, excision and vulvectomy. Gynecol Oncol. 2006;100:271–5.CrossRefGoogle Scholar
  21. 21.
    Winters U, Daayana S, Lear JT, et al. Clinical and immunologic results of a phase II trial of sequential imiquimod and photodynamic therapy for vulval intraepithelial neoplasia. Clin Cancer Res. 2008;14:5292–9.CrossRefGoogle Scholar
  22. 22.
    Tosti G, Iacobone AD, Preti EP, et al. The role of photodynamic therapy in the treatment of vulvar intraepithelial neoplasia. Biomedicine. 2018;2:6.Google Scholar
  23. 23.
    Yang A, Jeang J, Cheng K, et al. Current state in the development of candidate therapeutic HPV vaccines. Expert Rev Vaccines. 2016;15:989–1007.CrossRefGoogle Scholar
  24. 24.
    Cheng MA, Farmer E, Huang C, et al. Therapeutic DNA vaccines for human papillomavirus and associated diseases. Hum Gene Ther. 2018;9.
  25. 25.
    Kuroki LM, Frolova AI, Wu N, Liu J, Powell M, Thaker PH, Massad LS. Yield of cytology surveillance after high-grade vulvar intraepithelial neoplasia or cancer. J Low Genit Tract Dis. 2017;21:193–7.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  • Mario Preti
    • 1
  • Gianluigi Radici
    • 1
  • Leonardo Micheletti
    • 1
  1. 1.Department of Gynecology and ObstetricsUniversity of TorinoTorinoItaly

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