Stage 0 Vaginal Cancer
Vaginal Intraepithelial Neoplasia (VAIN) Including Squamous Cell Carcinoma In Situ
Squamous cell carcinoma in situ of the vagina is a lesion that falls within the more general category known as vaginal intraepithelial neoplasia (VAIN). VAIN, the presence of noninvasive squamous cell atypia, is associated with a high rate of human papillomavirus (HPV) infection and is thought to have a similar etiology as cervical intraepithelial neoplasia (CIN).[1-3] VAIN is classified by the degree of involvement of the epithelium: VAIN 1, 2, and 3 denote involvement of the upper one-third, two-thirds, and more than two-thirds of the epithelial thickness, respectively. Carcinoma in situ denotes VAIN 3 lesions that involve the full thickness of the epithelium. The FIGO staging system no longer includes vaginal carcinoma in situ (Stage 0) in its staging system, but it is retained in the AJCC staging system. Vaginal carcinoma in situ is often multifocal and commonly occurs at the vaginal vault. Because it is associated with other genital neoplasia, and in some cases may be an extension of CIN, the cervix (when present) and vulva should be carefully evaluated.
Women with VAIN 1 can usually be observed carefully without ablative or surgical treatment, since the lesions often regress spontaneously. The natural history of VAIN is not known with precision because of its rarity, but patients with VAIN 3 are felt to be at substantial risk of progression to invasive cancer and are treated immediately. The intermediate grade, VAIN 2, is variously managed by careful observation or initial treatment. The treatments listed below have not been compared directly in randomized trials, so their relative efficacy is uncertain.[Level of evidence 3iiiDiv] The selection of treatment depends on patient factors, anatomic location, evidence of multifocality, and local expertise (e.g., anatomical distortion of the vaginal vault related to wall closure at the time of prior hysterectomy requires excision for technical reasons to exclude the possibility of invasion by buried disease). Lesions with hyperkeratosis respond better to excision or laser vaporization than to fluorouracil.
Standard treatment options:
- Laser therapy. The lesions should first be sampled adequately to rule out invasive components that could be missed with this treatment approach.
- Wide local excision with or without skin grafting.
- Partial or total vaginectomy, with skin grafting for multifocal or extensive disease.
- Intravaginal chemotherapy with 5% fluorouracil cream. This option may be useful in the setting of multifocal lesions.[6,9]
- Intracavitary radiation therapy.[10,11] Because of its attendant toxicity and inherent carcinogenicity, this treatment is primarily used in the setting of multifocal or recurrent disease, or when the risk of surgery is high. The entire vaginal mucosa is usually treated.
Imiquimod cream 5%, an immune stimulant used to treat genital warts, is an additional topical therapy that has a reported complete clinical response rate of 50% to 86% in small case series of patients with multifocal high-grade HPV-associated VAIN 2 and 3. However, it is investigational, and it may have only short-lived efficacy.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage 0 vaginal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
- Eifel PJ, Berek JS, Markman MA: Cancer of the cervix, vagina, and vulva. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1311-44.
- Daling JR, Madeleine MM, Schwartz SM, et al.: A population-based study of squamous cell vaginal cancer: HPV and cofactors. Gynecol Oncol 84 (2): 263-70, 2002. [PUBMED Abstract]
- Smith JS, Backes DM, Hoots BE, et al.: Human papillomavirus type-distribution in vulvar and vaginal cancers and their associated precursors. Obstet Gynecol 113 (4): 917-24, 2009. [PUBMED Abstract]
- Vagina. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 387-9.
- Wright VC, Chapman W: Intraepithelial neoplasia of the lower female genital tract: etiology, investigation, and management. Semin Surg Oncol 8 (4): 180-90, 1992 Jul-Aug. [PUBMED Abstract]
- Krebs HB: Treatment of vaginal intraepithelial neoplasia with laser and topical 5-fluorouracil. Obstet Gynecol 73 (4): 657-60, 1989. [PUBMED Abstract]
- Cheng D, Ng TY, Ngan HY, et al.: Wide local excision (WLE) for vaginal intraepithelial neoplasia (VAIN). Acta Obstet Gynecol Scand 78 (7): 648-52, 1999. [PUBMED Abstract]
- Indermaur MD, Martino MA, Fiorica JV, et al.: Upper vaginectomy for the treatment of vaginal intraepithelial neoplasia. Am J Obstet Gynecol 193 (2): 577-80; discussion 580-1, 2005. [PUBMED Abstract]
- Stefanon B, Pallucca A, Merola M, et al.: Treatment with 5-fluorouracil of 35 patients with clinical or subclinical HPV infection of the vagina. Eur J Gynaecol Oncol 17 (6): 534, 1996. [PUBMED Abstract]
- Chyle V, Zagars GK, Wheeler JA, et al.: Definitive radiotherapy for carcinoma of the vagina: outcome and prognostic factors. Int J Radiat Oncol Biol Phys 35 (5): 891-905, 1996. [PUBMED Abstract]
- Graham K, Wright K, Cadwallader B, et al.: 20-year retrospective review of medium dose rate intracavitary brachytherapy in VAIN3. Gynecol Oncol 106 (1): 105-11, 2007. [PUBMED Abstract]
- Perez CA, Garipagaoglu M: Vagina. In: Perez CA, Brady LW, eds.: Principles and Practice of Radiation Oncology. 3rd ed. Philadelphia, Pa: Lippincott-Raven Publishers, 1998, pp 1891-1914.
- Iavazzo C, Pitsouni E, Athanasiou S, et al.: Imiquimod for treatment of vulvar and vaginal intraepithelial neoplasia. Int J Gynaecol Obstet 101 (1): 3-10, 2008. [PUBMED Abstract]
- Haidopoulos D, Diakomanolis E, Rodolakis A, et al.: Can local application of imiquimod cream be an alternative mode of therapy for patients with high-grade intraepithelial lesions of the vagina? Int J Gynecol Cancer 15 (5): 898-902, 2005 Sep-Oct. [PUBMED Abstract]