Human papillomavirus type 16 variants isolated from vulvar Bowenoid papulosis.

Tissues from two cases of Bowenoid papulosis of the vulva were found to contain human papillomavirus (HPV) 16 DNA by Southern blot hybridization. Analysis of the hybridization pattern revealed differences in a restriction fragment of one specimen as compared to the HPV 16 DNA prototype. To investigate if these differences could interfere with the expression of such oncogenic viral genomes, the corresponding DNA fragments were cloned and further analyzed. After amplification by PCR and DNA sequencing, a 213 base pairs duplication was mapped in the long control region (LCR) of this HPV 16 variant. One single PCR fragment was obtained from the other Bowenoid papulosis, which is identical in size with the same region in the HPV-16 prototype. The duplication in the HPV-16 LCR analyzed in this study maps upstream of a region containing several regulatory elements.

Differences in transformation activity between HPV-18 and HPV-16 map to the viral LCR-E6-E7 region.

Homologous, subgenomic fragments of the viral LCR and E6/E7 transforming genes of HPV-18 and HPV-16 were amplified from several primary cervical, penile, and vulvar tumors and cloned into a pUC-18-derived vector. When assayed by a quantitative transformation assay using primary human keratinocytes, the subgenomic regions of HPV-16 and HPV-18 exhibited transforming activities similar to that of the full-length, prototype HPV genomes. More importantly, the HPV-18 LCR-E6-E7 region was approximately 10- to 50-fold more active than that of HPV-16. These studies demonstrate (1) that the transforming activity differences previously observed between prototype HPV-16 and HPV-18 map to the LCR-E6-E7 region, and (2) that individual and independent isolates of HPV-16 and HPV-18 exhibit consistent differences in transforming potential, even when isolated from different anatomic sites.