Papillomaviruses in human disease: Part II. Molecular biology and immunology of papillomavirus infections and carcinogenesis.

As summarized in the last issue of the EJM, human papillomaviruses induce a great variety of neoplastic lesions of mucosal epithelia and the skin. Particular types of these viruses are associated with specific human cancers, most notably anogenital carcinomas. These tumours account for about fifteen percent of the whole worldwide cancer burden. However, recent epidemiological studies revealed that papillomavirus infections including those with the cancer-related papillomavirus types are very widespread even among asymptomatic healthy individuals. Here, the current understanding of the molecular events leading to papillomavirus-induced tumours will be reviewed. It is assumed that these tumours arise as a consequence of several molecular modifications of persistently papillomavirus-infected epithelial cells. Experimental studies revealed that the virus types associated with anogenital cancers harbour two potential oncogenes referred to as E6 and E7. These viral genes are consistently expressed in HPV-associated anogenital carcinoma cells. HPV-associated cervical carcinoma cells loose their neoplastic growth properties if the expression of the E6 and E7 genes is inhibited. The proteins encoded by these viral genes thus appear to be ideal targets for a specific pharmacological approach to treat papillomavirus associated cancers or their respective precursor lesions. Recent studies in animals furthermore suggest that active vaccination with the viral oncoprotein E7 prevents growth of papillomavirus associated tumours. Hence, the possibility arises that also in man, vaccination with the viral transforming proteins might prevent the development of papillomavirus associated cancers.