Expression of the E6 and E7 Genes of Human Papillomaviruses in Tumors of Different Dignity

Abstract

The E6 and E7 genes of genital human papillomaviruses (HPV) immortalize keratino-cytes and the E6/7 segment of the viral genome appears to be transcribed in most, if not all, HPV-positive cancers (zur Hausen, 1991). The E6 and E7 proteins are therefore regarded as good candidates for immunotherapy. In situ hybridization studies with HPV16-infected low grade cervical lesions showed only very weak transcription of E6 / E7 in the basal layer, whereas expression strongly increased in the more differentiated layers accompanied by high levels of DNA replication (Durst et al. 1992; Stoler et al. 1992). In high grade squamous intraepithelial lesions, transcription of the E6 / E7 region appeared derepressed, and in situ hybridization signals were evenly distributed throughout the undifferentiated epithelium. The initial studies did not distinguish between mRNAs specific for E6 and E7. Another potential. problem was the use of an anti-sense RNA probe covering the complete ORFs E6 and E7 for the detection of HPV 16 E6 / E7 mRNA. Such probes may hybridize with the 5’ ends of E1^4 transcripts, which predominate in HPV 6-induced condylomas (Nasseri et al. 1987), and also seem to exist in low grade HPV 16-infected intraepithelial. neoplasias (Higgins et al., 1992). We therefore designed new probes for in situ hybridization which specifically detect transcripts with a coding potential. for E6 and E7, respectively, taking into account more recent data on HPV transcription strategies.