Epidermodysplasia Verruciformis and Cutaneous Human Papillomavirus DNA, but Not Genital Human Papillomavirus DNAs, Are Frequently Detected in Vulvar and Vaginal Melanoma

Vulvovaginal melanomas are rare and their etiology is unknown. Genital mucosal human papillomavirus (HPV) 16 has been identified in both cutaneous and mucosal melanoma, suggesting that it might play a role in the pathogenesis or progression of melanoma. In this study, we investigated the prevalence of HPV DNA by using a broad spectrum of degenerate and type-specific primers for genital-mucosal, epidermodysplasia verruciformis-associated (EV), and cutaneous HPV types in 6 vulvar and 3 vaginal melanomas. The patients were mostly postmenopausal women (8/9), had a mean age of 67 years (range, 44-85 years), and had mucosal lentiginous (7) or nodular (2) melanomas. In the adjacent skin/mucosa, mucosal melanosis was found in 5, lichen sclerosus or a lichenoid mucositis in 4, and blue nevi in 2 women. With nested polymerase chain reaction techniques followed by direct sequencing, HPV DNA was identified in 6 of 9 (67%) melanomas; these were either cutaneous (HPV 3) (4/9) or epidermodysplasia verruciformis-associated types (HPV 38, Z95969, AJ00151) (4/9). Epidermodysplasia verruciformis-associated HPV (type 15) was found solely in 1/10 (10%) normal vulvar controls. Genital-mucosal HPV types were not detected either by degenerate nested polymerase chain reaction or type-specific probes for HPV 16. We propose that the above findings are not coincidental but may represent a molecular record of HPV involvement in pathogenesis or progression of melanoma, which is consistent with the strong but poorly defined association of cutaneous HPV types with nonmelanoma skin cancers. The theory that HPV may act as a cofactor in melanoma development deserves further clinical and experimental investigations.