The
DNA genome of a human papillomavirus (HPV), tentatively designated HPV-EV, was molecularly cloned from hand to leg lesions of a patient with
epidermodysplasia verruciformis, a chronic
skin disease associated with a 30% risk of developing
cancer. Using stringent hybridization conditions, we observed less than 5% homology between HPV-EV and the cloned genomes of HPV-1, HPV-4, HPV-5, and HPV-5a. HPV-EV
DNA showed approximately 6% homology with HPV-2 and 36% homology with HPV-3. These data suggest that HPV-EV is partially related to HPV-3. Using 32P-labeled cloned HPV-EV as probe in Southern blot hybridization experiments, we detected HPV-EV-related
DNA 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 two patients with condyloma acuminata (anogenital
warts), which is of interest considering that condylomas have been reported to convert occasionally to
carcinomas. The positive vulva DNAs were also probed with other cloned HPV DNAs: 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, our findings are consistent with the idea, but by no means establish, that HPVs play a role in human
cancer by a similar mechanism.