Vaginal Intraepithelial Neoplasia (VAIN) Including Squamous Cell CarcinomaIn 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).[1,2,3] 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.
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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.