CHARACTERIZATION OF HUMAN PAPILLOMAVIRUS TYPE-16 ACTIVITY IN SEPARATEBIOPSIES FROM A CARCINOMA OF THE CERVIX UTERI

Human papillomavirus (HPV)16-specific nucleic acid sequences were anal ysed in separate biopsies taken from a patient with a poorly different iated squamous cell carcinoma of the uterine cervix. Biopsies were obt ained from histopathologically normal epithelium adjacent to the carci nomatous epithelium, the primary carcinoma and a metastatic lymph node . Signals characterizing viral DNA and oncogene transcription were obv iously differentiation dependent as shown by in situ hybridization of viral nucleic acids and immunofluorescence of epithelial differentiati on specific proteins. In histologically normal parts of the epithelium viral DNA was amplified at the transition from basal to maturing cell s, whereas E6/E7 genes were actively transcribed mainly in maturing ep ithelial cells following the basal cell layer. Some of the cells in th e primary carcinoma and in the metastatic lymph node expressed involuc rin at increased levels. Signals for viral DNA and HPV16-specific E6/E 7 transcripts decreased in intensity during differentiation in an inve rse relationship to the observed involucrin increase in those cells. T he absence of Ki67 in cells expressing large amounts of involucrin as revealed by immunostaining, support the inverse correlation between di fferentiation of cancer cells, HPV16 replication and E6/E7 transcripti on. The changes in cytokine expression may indicate an HPV16 associate d disruption of normal cytokine expression pattern in the carcinoma.