This review discusses diseases of the lower genital tract in which the presence of human papillomavirus (HPV) DNA is well documented. We discuss epidemiologic, clinical, and experimental data supporting a causative role for HPV in mucosal malignancies, with emphasis on the role of viral and host factors in their pathogenesis. Of special interest is the recently discovered association of cutaneous tumors with HPVs, previously known only for tumors in epidermodysplasia verruciformis (EV). The frequent detection of EV-specific or EV-related HPVs in immunosuppressed persons and in cutaneous tumors in the general population supports the importance of EV as a model of cutaneous oncogenesis. We also discuss recent serologic findings based on enzyme-linked immunosorbent assay results with the use of viruslike particles. This is important both for detection of present or past HPV infection and for epidemiologic and immunologic studies. Novel therapeutic modalities for HPV tumors and prospects for prophylactic and therapeutic vaccination are presented.