Characterization of human papillomavirus type 16 activity in separate biopsies from a carcinoma of the cervix uteri.

Human papillomavirus (HPV) 16-specific nucleic acid sequences were analysed in separate biopsies taken from a patient with a poorly differentiated squamous cell carcinoma of the uterine cervix. Biopsies were obtained from histopathologically normal epithelium adjacent to the carcinomatous epithelium, the primary carcinoma and a metastatic lymph node. Signals characterizing viral DNA and oncogene transcription were obviously differentiation dependent as shown by in situ hybridization of viral nucleic acids and immunofluorescence of epithelial differentiation specific proteins. In histologically normal parts of the epithelium viral DNA was amplified at the transition from basal to maturing cells, whereas E6/E7 genes were actively transcribed mainly in maturing epithelial cells following the basal cell layer. Some of the cells in the primary carcinoma and in the metastatic lymph node expressed involucrin at increased levels. Signals for viral DNA and HPV 16-specific E6/E7 transcripts decreased in intensity during differentiation in an inverse relationship to the observed involucrin increase in those cells. The absence of Ki67 in cells expressing large amounts of involucrin as revealed by immunostaining, support the inverse correlation between differentiation of cancer cells, HPV 16 replication and E6/E7 transcription. The changes in cytokine expression may indicate an HPV 16 associated disruption of normal cytokine expression pattern in the carcinoma.