Isolation of a human papillomavirus from a patient with epidermodysplasia verruciformis: presence of related viral DNA genomes in human urogenital tumors.

Abstract
The DNA genome of a human papillomavirus (HPV), tentatively designated HPV-EV, was molecularly cloned from hand and leg lesions of a patient with epidermodysplasia verruciformis, a chronic skin disease associated with a 30% risk of developing cancer. Using stringent hybridization conditions, < 5% homology was observed between HPV-EV and the cloned genomes of HPV-1, HPV-4, HPV-5 and HPV-5a. HPV-EV DNA showed .apprx. 6% homology with HPV-2 and 36% homology with HPV-3. HPV-EV thus appears to be partially related to HPV-3. Using 32P-labeled cloned HPV-EV as probe in Southern blot hybridization experiments, HPV-EV-related DNA was detected in the carcinoma in situ (Bowenoid lesion) of the vulva of the patient from which HPV-EV was isolated. HPV-EV-related DNA was detected in 2 of 10 vulva carcinomas and in 2 of 31 cervical carcinomas. Related DNA sequences were found in papillomas from each of 2 patients with condyloma acuminata (anogential warts), which is of interest considering that condylomas were reported to convert occasionally to carcinomas. The positive vulva DNA were also probed with other cloned HPV DNA: HPV-1-, HPV-4- and HPV-5a-related sequences were not detected; HPV-3 and HPV-2 DNA probes detected strong and weak DNA bands, respectively, of the same size as found with HPV-EV. The HPV DNA sequences were present in the positive tumors mainly as free viral DNA molecules; no evidence for integration into cellular DNA was found. The emerging biological picture with papillomaviruses is that cells transformed by these viruses are maintained in a transformed state by free episomal genomes. Thus, these findings are consistent with the idea, but by no means establish, that HPV play a role in human cancer by a similar mechanism.