Papillomaviruses causing cancer: Evasion from host-cell control in early events in carcinogenesis

During the past 20 years, several types of human papillomaviruses (HPVs) ha ve been identified that cause specific types of cancers. The etiology of ca ncer of the cervix has been linked to several types of HPV, with a high pre ponderance of HPV16, The role of these virus infections has been establishe d 1) by the regular presence of HPV DNA in the respective tumor biopsy spec imens, 2) by the demonstration of viral oncogene expression (E6 and E7) in tumor material, 3) by the identification of transforming properties of thes e genes, 4) by the requirement for E6 and E7 expression for maintaining the malignant phenotype of cervical carcinoma cell lines, 5) by the interactio n of viral oncoproteins with growth-regulating host-cell proteins, and 6) b y epidemiologic studies pointing to these HPV infections as the major risk factor for cervical cancer development. In addition to cancer of the cervix , a major proportion of anal, perianal, vulvar, and penile cancers appears to be linked to the same HPV infections. In addition, close to 20% of oroph aryngeal cancers contain DNA from the same types of HPV, Recent evidence al so points to a possible role of other HPV infections in squamous cell carci nomas of the skin. This review covers recent developments in understanding molecular mechanisms of HPV carcinogenesis, mainly discussing functions of viral oncoproteins and the regulation of viral oncogenes by host-cell facto rs. Modifications in host-cell genes, most likely engaged in the control of HPV gene expression in proliferating cells, emerge as important events in HPV-mediated carcinogenesis.