A subset of human papillomaviruses (the high risk types of HPV) have been associated with anogenital cancers. In malignant lesions, the viral DNA is usually found integrated into the host chromosome which prevents productive replication and is in contrast to the extrachromosomal form of the genome which is present during productive replication. Studies are proposed to determine whether specific sites of viral integration or viral mutations that prevent maintenance of HPV genomes as extrachromosomal elements are important during progression to malignancy. The two sets of questions to be addressed by examining a large collection of biopsy samples of cervical carcinomas are: 1. What is the state of the HPV DNA in these samples? Are specific sites of integration important and are the tumors clonal with respect to the state and expression of the viral sequences? 2. Integration often disrupts the E1 and E2 ORFs which are involved in both genome replication as well as transcriptional regulation of the HPV early region. Are there differences between episomal and integrated HPV DNAs in the nucleotide sequences in the E1 and E2 ORFs? If so, what is the effect of these mutations on the genome replication capabilities?
