Vulvar malignant melanoma associated with human papillomavirus DNA: report of two cases and review of literature

Oncogenic human papillomavirus (HPV) types such as HPV 16 are known to play a crucial role in the development of anogenital carcinomas. The etiology of anogenital malignant melanoma is unknown. We report two case of vulvar malignant melanoma in which multiple HPV types including HPV 16 and putative novel HPV types (alb-1, alb-2, alb-7, and alb-10) were identified by degenerated nested polymerase chain techniques (polymerase chain reaction) in both the malignant melanoma and surrounding skin. One melanoma was associated with lichen sclerosus, and the other, with melanoma in situ and pigmented vulvar squamous papillomatosis. These melanomas harbored HPV types alb-7, and HPV 16 as well as alb-1, respectively. HPV types 16, 20, 21, 36, alb-2, and AJ001060 were detected in vulvar skin affected by lichen sclerosus. Vulvar squamous papillomatosis harbored HPV types 28 and alb-10. HPV 16 was physically integrated into the host genome in lichen sclerosus skin and possibly in the melanoma associated with pigmented vulvar squamous papillomatosis. Twenty-two percent (4 of 18) of normal control specimens from skin tumor excisions were found to harbor HPV DNA (HPV types 3, 54, and alb-7); none of these control samples harbored multiple HPV DNA. These findings of multiple HPV DNA and integrated HPV 16 in skin associated with vulvar malignant melanoma indicate that HPV may play a role in the development of vulvar malignant melanoma. The role of HPV could be either direct through infection of melanocytes or indirect as a cofactor with free radicals in chronic fibroinflammatory vulvar disorders such as lichen sclerosus.