8.
The use of preoperative radiation therapy to obviate the need for exenteration in patients with advanced disease.
9.
The use of postoperative radiation therapy to decrease the incidence of groin recurrence in patients with multiple positive groin nodes.
The etiology of vulvar cancer is only partially elucidated and likely to be multifactorial. Reported risk factors for vulvar cancer include human papillomavirus (HPV) infection, vulvar intra-epithelial neoplasia (VIN), cervical intraepithelial neoplasia (CIN), lichen sclerosus, squamous hyperplasia, cigarette smoking, alcohol consumption, immunosuppression, a prior history of cervical cancer, and northern European ancestry (8,9). Based on histopathologic and environmental factors, there appear to be at least two distinct etiologic entities of squamous cell carcinoma of the vulva: 1.
Basaloid or warty types, which tend to be multifocal, occur generally in younger patients and are related to HPV infection, VIN, and cigarette smoking.
2.
Keratinizing, differentiated, or simplex types, which tend to be unifocal, occur predominantly in older patients, are not related to HPV, and often are found in areas adjacent to lichen sclerosus and squamous hyperplasia.
High-grade vulvar intraepithelial neoplasia (VIN 3) was closely studied as a potential precancerous lesion. The direct progression of VIN to cancer is difficult to document, but a review of 3,322 published patients with VIN 3 reports a 9% progression rate to cancer for untreated cases (10). VIN is found adjacent to basaloid or warty vulvar squamous cell carcinomas in more than 80% of cases and 10% to 20% of vulvar carcinoma in situ lesions harbor an occult invasive component (11,12). HPV DNA is documented in 89% of patients with VIN 3, in 60% of vulvar cancers overall, and in up to 86% of warty or basaloid type carcinomas of the vulva; but it occurs in less than 10% of the keratinizing type of carcinomas of the vulva (13). HPV 16 and 33 are the prevalent subtypes, accounting for 55.5% of all HPV-related vulvar cancers (14). Epidemiologic risk factors for the basaloid or warty type squamous cell carcinoma of the vulva are similar to those for cervical cancer and include a history of multiple lower genital tract neoplasias, immunosuppression, and smoking (13,15).
Frequently implied as an etiologic variable for the keratinizing carcinoma is the itch–scratch cycle associated with lichen sclerosus and squamous hyperplasia, with atypical changes occurring in the repaired epithelium. Differentiated (or simplex) VIN is a precursor to squamous cell carcinoma and is associated with lichen sclerosus. In keratinizing carcinoma, associated lichen sclerosus or squamous hyperplasia is found in more than 80% of patients (16,17). Women with vulvar lichen sclerosus are at increased risk of developing invasive squamous cell