Papillomavirus Infections and Cancerogenesis of Squamous Cell and Basal Cell Carcinomas

Abstract

Human papillomaviruses (HPVs) are a large group of infectious agents that induce various lesions of skin and mucosae. The carcinogenic role of HPV types 16 and 18, mediated by inactivation of the tumor suppressor proteins p53 and pRb by the viral oncoproteins E6 and E7, is established for cervical cancer. For cutaneous carcinogenesis, a causative role of HPVs is so far recognized only for squamous cell carcinomas (SCCs) in the rare heriditary skin disease epidermodysplasia verruciformis (EV). In both cervical cancer and SCCs of EV patients HPV DNA persists in high copy numbers, and the viral oncogenes E6 and E7 are transcribed at high levels. The detection of HPV DNA in SCCs and their precursors in individuals without EV history raises the question of the oncogenic role of HPVs in cutaneous tumors of the general population and particularly in the situation of iatrogenic immunosuppression. Polymerase chain reaction procedures revealed that HPVs of all subgroups are ubiquitous agents. But in the nonEV population, HPV concentration in both skin tumors and premalignant lesions is extremely low with only 1 HPV DNA copy on 20 to 5000 host cells. A number of in vitro observations suggest a transforming potential of HPV- encoded proteins or their interaction with cell cycle control in ultraviolet radiation-damaged skin. The chapter presents a critical analysis of these data with regard to their clinical significance.