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Journal of General Virology (2000), 81, 1825-1832.
© 2000 Society for General Microbiology


Animal: DNA Viruses

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

Mark Stevenson1, Lucy C. Hudson1, Julie E. Burns1, Roy L. Stewart2, Michael Wells2 and Norman J. Maitland1

YCR Cancer Research Unit, Department of Biology, University of York, York YO10 5YW, UK1
Division of Oncology and Cellular Pathology, University of Sheffield Medical School, Sheffield S10 2RX, UK2

Author for correspondence: Norman Maitland. Fax +44 1904 432615. e-mail njm9{at}york.ac.uk

The human papillomavirus type 16 (HPV-16) status of 43 cervical biopsies, which had been characterized histologically as normal, various grades of cervical 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/PCR 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 highest levels in carcinoma cells. Co-localization of E2 with HPV-16 DNA-positive cells was most commonly observed in koilocytes in CIN II lesions. PCR analyses of microdissected epithelium from the same or serial sections indicated that E2 ORFs were retained in an intact form in a number of higher-grade CIN lesions and invasive carcinomas.




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