Inverse relationship between the expression of the human papillomavirus type 16 transcription factor E2 and virus DNA copy number during the progression of cervical intraepithelial neoplasia

The human papillomavirus type 16 (HPV-16) status of 43 cervical biopsies, w hich had been characterized histologically as normal, various grades of cer vical intraepithelial neoplasia (CIN) and invasive squamous cell carcinoma, was examined by using (i) a novel antibody against the HPV-16 E2 protein, (ii) sensitive HPV-16 DNA in situ hybridization and (iii) microdissection/P CR for the E2 ORF, The data indicate that E2 protein expression is highest in koilocytes in lower-grade CIN (I), but decreases with increasing grade, whereas the detection of HPV DNA is delayed until CIN I/II, rising to the h ighest levels in carcinoma cells. Go-localization of E2 with HPV-16 DNA-pos itive cells was most commonly observed in koilocytes in CIN II lesions. PGR analyses of microdissected epithelium from the same or serial sections ind icated that E2 ORFs were retained in an intact form in a number of higher-g rade GIN lesions and invasive carcinomas.