Papillomaviruses in human cancer

Twelve types of human papillomaviruses (HPV) have been isolated thus far from papillomatous and Bowenoid lesions of the human genital tract. Four type, HPV 6, 11, 16 and 18 are most frequently found. HPV 6 and 11 cause the typical genital warts (condylomata acuminata) and mild dysplastic lesions of the cervix characterized by a high degree of koilocytotic atypia. HPV 16 and 18 are preferentially found in Bowenoid papulosis and Bowen's disease at external genital sites. Moderate and severe cervical dysplasias with little or no koilocytosis appear to be common manifestations of these infections at cervical sites. HPV 16 is found in approximately 50% of all cervical, penile and vulvar cancers, HPV 18 in close to 20%. The majority of the remaining tumors reveals evidence for infections with additional types of HPV. Several cell lines have been identified containing either HPV 18 or HPV 16 genomes. The state of viral DNA in Bowenoid precursor lesions differs from that of cervical carcinomas. The former contain episomal DNA whereas integration seems to be a regular event in carcinomas. Integration regularly affects the E1-E2 open reading frames of HPV 16 or HPV 18 DNA. Fusion transcripts from the integrated HPV DNA (E6-E7 region) and adjacent host cell DNA have been documented. The available data support a causative role of specific HPV infections in the etiology of human genital cancer.