Papillomaviruses in human cancers

Papillomaviruses have proved to be the most complex group of human pathogen ic viruses. Eighty-five genotypes have been fully characterized; approximat ely 120 additional isolates represent only partially characterized putative novel genotypes. Specific types, most notably human papillomavirus (HPV) t ypes 16, 18, and a few others, have been shown to cause the majority of cer vical cancers and their high-grade precursor lesions. The viral oncogenes E 6 and E7 are required for the initiation and maintenance of the malignant p henotype in HPV-positive cancers. Proteins coded by these genes are multifu nctional and interfere with important cell cycle regulatory proteins. Expre ssion of viral oncogenes is tightly controlled in nondifferentiated keratin ocytes by at least two signaling cascades, one operative at the functional level, the other at the transcriptional level. The latter has been partiall y characterized. Papillomaviruses are also suspected of playing a role in a subset of oropharyngeal cancers, in squamous cell cancers of the skin, and possibly also in esophageal cancers. Clinical trials are being conducted t o test the preventive and therapeutic efficacy of HPV vaccines, directed pa rticularly against HPV 16 and 18. If proven to be effective, their global a pplication should have a measurable effect on the worldwide incidence of ca ncer.