Prämaligne Vulvaläsionen: Einteilung, Risikofaktoren und Therapieoptionen

Bei vulvären intraepithelialen Neoplasien (VIN) handelt es sich um plattenepitheliale Dysplasien der Vulva. In den letzten Jahrzehnten zeigt sich weltweit eine steigende Inzidenz dieser Vorstufen des Vulvakarzinoms. Dieser Beitrag liefert einen Überblick über die Subtypen der Vulvadysplasien und stellt die Behandlungsoptionen von chirurgischer Exzision über Laservaporisation bis hin zu den medikamentösen Therapiemöglichkeiten vor.

Schlüsselwörter

Vulväre intraepitheliale Neoplasie - HPV-assoziierte VIN - HPV-unabhängige VIN - Imiquimod

• Literatur

• 1 Höhn AK, Brambs CE, Hiller GGR. et al. 2020 WHO Classification of Female Genital Tumors. Geburtshilfe Frauenheilkd 2021; 81: 1145-1153
• 2 Darragh TM, Colgan TJ, Thomas Cox J. 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: 76-115
• 3 Tessier-Cloutier B, Kortekaas KE, Thompson E. et al. Major p53 immunohistochemical patterns in in situ and invasive squamous cell carcinomas of the vulva and correlation with TP53 mutation status. Mod Pathol 2020; 33: 1595-1605
• 4 Deutsche Gesellschaft für Gynäkologie und Geburtshilfe e.V. (DGGG) (federführend). S2k-Leitlinie. Diagnostik, Therapie und Nachsorge des Vulvakarzinoms und seiner Vorstufen. Registernr. 015/059. 2015 Zugriff am 05. Juni 2024 unter: https://register.awmf.org/de/leitlinien/detail/015–059OL
• 5 Judson PL, Habermann EB, Baxter NN. et al. Trends in the incidence of invasive and in situ vulvar carcinoma. Obstet Gynecol 2006; 107: 1018-1022
• 6 Joura EA, Lösch A, Haider-Angeler MG. et al. Trends in vulvar neoplasia. Increasing incidence of vulvar intraepithelial neoplasia and squamous cell carcinoma of the vulva in young women. J Reprod Med 2000; 45: 613-615
• 7 Del Pino M, Rodriguez-Carunchio L, Ordi J. Pathways of vulvar intraepithelial neoplasia and squamous cell carcinoma. Histopathology 2013; 62: 161-175
• 8 Paul-Ehrlich-Gesellschaft für Infektionstherapie e.V. (PEG) (federführend). S3-Leitlinie Impfprävention HPV-assoziierter Neoplasien. Registernr. 082–002. 2020 Zugriff am 27. Februar 2024 unter: https://register.awmf.org/de/leitlinien/detail/082–002
• 9 Münger K, Howley PM. Human papillomavirus immortalization and transformation functions. Virus Res 2002; 89: 213-228
• 10 Liao MJ, Lai CH. The distribution of HPV subtype in vulvar intraepithelial neoplasia and the association with recurrent VIN and vulva cancer in Taiwan. Journal of Clinical Oncology 2023; 41: e17635-e17635
• 11 Massad LS, Xie X, Darragh T. et al. Genital warts and vulvar intraepithelial neoplasia: natural history and effects of treatment and human immunodeficiency virus infection. Obstet Gynecol 2011; 118: 831-839
• 12 Bleeker MCG, Visser PJ, Overbeek LIH. et al. Lichen Sclerosus: Incidence and Risk of Vulvar Squamous Cell Carcinoma. Cancer Epidemiol Biomarkers Prev 2016; 25: 1224-1230
• 13 Thuijs NB, van Beurden M, Bruggink AH. et al. Vulvar intraepithelial neoplasia: Incidence and long-term risk of vulvar squamous cell carcinoma. Int J Cancer 2021; 148: 90-98
• 14 Thuijs NB, van Beurden M, Duin S. et al. High-grade vulvar intraepithelial neoplasia: comprehensive characterization and long-term vulvar carcinoma risk. Histopathology 2023; 84: 301-314
• 15 van de Nieuwenhof HP, Massuger LFAG, van der Avoort IAM. et al. Vulvar squamous cell carcinoma development after diagnosis of VIN increases with age. Eur J Cancer 2009; 45: 851-856
• 16 van Seters M, van Beurden M, de Craen AJM. Is the assumed natural history of vulvar intraepithelial neoplasia III based on enough evidence? A systematic review of 3322 published patients. Gynecol Oncol 2005; 97: 645-651
• 17 Bornstein J, Sideri M, Tatti S. et al. 2011 terminology of the vulva of the International Federation for Cervical Pathology and Colposcopy. J Low Genit Tract Dis 2012; 16: 290-295
• 18 Küppers V, Gallwas J. Vulvadiagnostik. Frauenheilkunde up2date 2023; 17: 377-395
• 19 Lellé RJ, Küppers V. Anormale Befunde der Zervix. In: Lellé RJ, Küppers V. Kolposkopie in der Praxis [mit 73 klinischen Szenarien]. 2. Berlin, Heidelberg: Springer; 2014: 13-37
• 20 Grimm D, Eulenburg C, Brummer O. et al. Sexual activity and function after surgical treatment in patients with (pre)invasive vulvar lesions. Support Care Cancer 2016; 24: 419-428
• 21 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: 271-275
• 22 Leufflen L, Baermann P, Rauch P. et al. Treatment of vulvar intraepithelial neoplasia with CO(2) laser vaporization and excision surgery. J Low Genit Tract Dis 2013; 17: 446-451
• 23 Satmary W, Holschneider CH, Brunette LL. et al. Vulvar intraepithelial neoplasia: Risk factors for recurrence. Gynecol Oncol 2018; 148: 126-131
• 24 Wallbillich JJ, Rhodes HE, Milbourne AM. et al. Vulvar intraepithelial neoplasia (VIN 2/3): comparing clinical outcomes and evaluating risk factors for recurrence. Gynecol Oncol 2012; 127: 312-315
• 25 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: 1465-1473
• 26 Pepas L, Kaushik S, Nordin A. et al. Medical interventions for high-grade vulval intraepithelial neoplasia. Cochrane Database Syst Rev 2015; 2015 (08) CD007924
• 27 Trutnovsky G, Reich O, Joura EA. et al. Topical imiquimod versus surgery for vulvar intraepithelial neoplasia: a multicentre, randomised, phase 3, non-inferiority trial. Lancet 2022; 399: 1790-1798
• 28 Wölber L. Update Gynäkologische Onkologie 2023/2024. Vulva-Erkrankungen. 2023 Gyn-Onko Update. ISBN 978-3-98769-212-3
• 29 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: 1361-1368
• 30 Hurt CN, Jones S, Madden TA. et al. Recurrence of vulval intraepithelial neoplasia following treatment with cidofovir or imiquimod: results from a multicentre, randomised, phase II trial (RT3VIN). BJOG 2018; 125: 1171-1177
• 31 Disbrow GL, Baege AC, Kierpiec KA. et al. Dihydroartemisinin is cytotoxic to papillomavirus-expressing epithelial cells in vitro and in vivo. Cancer Res 2005; 65: 10854-10861
• 32 Trimble CL, Levinson K, Maldonado L. et al. A first-in-human proof-of-concept trial of intravaginal artesunate to treat cervical intraepithelial neoplasia 2/3 (CIN2/3). Gynecol Oncol 2020; 157: 188-194
• 33 Michener CM, Ricci S, AlHilli M. et al. Safety and efficacy of topical artesunate for the treatment of vulvar intraepithelial neoplasia 2/3. Gynecol Oncol 2023; 178: 102-109
• 34 Lifshitz S, Roberts JA. Treatment of carcinoma in situ of the vulva with topical 5-fluorouracil. Obstet Gynecol 1980; 56: 242-244
• 35 González Rodríguez SP, García-Iglesias A, García Valle S. et al. Comparative study of the topical treatments for human papilloma virus infection of the vulva. 2005 Zugriff am 24. Juni 2024 unter: https://tspace.library.utoronto.ca/bitstream/1807/9247/1/va05010.pdf
• 36 Krebs HB. Prophylactic topical 5-fluorouracil following treatment of human papillomavirus-associated lesions of the vulva and vagina. Obstet Gynecol 1986; 68: 837-841
• 37 Rasmussen CL, Thomsen LT, Aalborg GL. et al. Incidence of vulvar high-grade precancerous lesions and cancer in Denmark before and after introduction of HPV vaccination. Gynecol Oncol 2020; 157: 664-670
• 38 Joura EA, Leodolter S, Hernandez-Avila M. et al. Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal lesions: a combined analysis of three randomised clinical trials. Lancet 2007; 369: 1693-1702
• 39 Joura EA, Garland SM, Paavonen J. et al. Effect of the human papillomavirus (HPV) quadrivalent vaccine in a subgroup of women with cervical and vulvar disease: retrospective pooled analysis of trial data. BMJ 2012; 344: e1401
• 40 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: 1061-1067
• 41 Kurman RJ, Carcangiu ML, Herrington CS. World Health Organisation Classification of Tumours of the Female Reproductive Organs. 2014 WHO Classification of Tumours. 4th ed., Vol. 6, 2014. ISBN 13978-92-832-2435-8
• 42 Shaco-Levy R, Bean SM, Vollmer RT. et al. Paget disease of the vulva: a histologic study of 56 cases correlating pathologic features and disease course. Int J Gynecol Pathol 2010; 29: 69-78
• 43 Shiomi T, Noguchi T, Nakayama H. et al. Clinicopathological study of invasive extramammary Paget’s disease: subgroup comparison according to invasion depth. J Eur Acad Dermatol Venereol 2013; 27: 589-592
• 44 Delport ES. Extramammary Paget’s disease of the vulva: An annotated review of the current literature. Australas J Dermatol 2013; 54: 9-21
• 45 Schnürch HG, Ackermann S, Alt CD. et al. Diagnosis, Therapy and Follow-up Care of Vulvar Cancer and its Precursors. Guideline of the DGGG and DKG (S2k-Level, AWMF Registry Number 015/059, November 2015). Geburtshilfe Frauenheilkd 2016; 76: 1035-1049
• 46 van der Linden M, Oonk MHM, van Doorn HC. et al. Vulvar Paget disease: A national retrospective cohort study. J Am Acad Dermatol 2019; 81: 956-962
• 47 Machida H, Moeini A, Roman LD. et al. Effects of imiquimod on vulvar Paget’s disease: a systematic review of literature. Gynecol Oncol 2015; 139: 165-171
• 48 van der Linden M, van Hees CL, van Beurden M. et al. The Paget Trial: topical 5% imiquimod cream for noninvasive vulvar Paget disease. Am J Obstet Gynecol 2022; 227: 250.e1-250.e8