Human Papillomavirus: Detection of Viral DNA Sequences and Evidence for Molecular Heterogeneity in Metaplasias and Dysplasias of the Uterine Cervix

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Abstract
Colposcopic-directed biopsies of the uterine cervix from 22 patients were analyzed for the presence of human papillomavirus (HPV) DNA and structural antigens. 11 of the biopsies were classified microscopically as mild dysplasia, 3 as moderate dysplasia, 1 as severe dysplasia, and 7 as squamous metaplasia. Nonstringent hybridization with a bovine papillomavirus type 1 DNA probe and immunocytochemical analysis with an antiserum against papillomavirus genus-specific structural antigens were performed on all specimens. Of the 11 mild dysplasias, both HPV DNA and structural antigens were detected in 5, only HPV antigens in 3, only HPV DNA in 1, and neither DNA nor structural antigens in 2. Both HPV DNA and structural antigens were present in the 3 cases of moderate dysplasia. Only HPV DNA sequences were detected in the single case of severe dysplasia. HPV DNA was detected in 2 cases of squamous metaplasia. The 5 remaining cervical biopsies showing squamous metaplasia, tissue from 3 placentas, and 6 cervical carcinomas were negative for HPV DNA and structural antigens. Restriction enzyme cleavage patterns of HPV DNA in the dysplasias suggested that there are multiple virus types or subtypes associated with cervical dysplasia. Stringent hybridization with a HPV type 11 (HPV-11) probe revealed that only 1 of 10 dysplasias contained sequences with homology to the probe. Of the remaining 9 dysplasias, 5 contained HPV sequences detected under nonstringent hybridization. 2 of 4 squamous metaplasias contained viral sequences which hybridized to the HPV-11 probe as well as 1 of 6 cervical carcinomas.