Abstract
High-risk human papillomavirus types, especially type 16, are risk factors for cervical cancer. Preliminary studies suggest that HPV16 polymorphisms in the long control region or in the E6 gene may alter the oncogenic potential of the virus. This could partially explain why some lesions progress to cancer while others do not. A systematic study combining the long control region and E6 has not been undertaken. This prompted us to investigate the long control region and the E6 in northern European women infected with human papillomavirus 16. We identified the sequence variations of both regions and investigated the long control region promoter activity among various isolates. In addition, we correlated the distribution of long control region and E6 polymorphisms with disease status. We analyzed 45 samples from Swedish and Finnish women. The long control region and the E6 gene were sequenced after polymerase chain reaction long control region fragments of six European isolates covering the majority of polymorphisms in this region were ligated into the pALuc vector and used for luciferase assays. In European HPV16 isolates, polymorphisms in the long control region are more frequent than in the E6 gene. Nevertheless, the promoter function was slightly increased in only one of the tested European long control region variants. In addition, we found a specific European E6 variant, L83V, to be enriched in high-grade lesions and cancer rather than a specific European long control region variant. The difference in oncogenicity between European HPV16 genotypes is more probably due to an altered property of the corresponding E6 proteins rather than to an altered activity of the P97 promoter.British Journal of Cancer (2002) 86, 269–273. DOI: 10.1038/sj/bjc/6600024 www.bjcancer.com© 2002 The Cancer Research Campaign
Highlights
The objective of this study was to determine the long control region (LCR) and the E6 sequences of HPV16 from north European women and to establish whether there are differences in promoter activity between the genotypes identified
We found polymorphisms in the LCR to be more common than polymorphisms in the E6 gene in European isolates
The Swedish samples are derived from a cross-sectional study consisting of extracted DNA from formalin-fixed cervical biopsies diagnosed as having low-grade or high-grade cervical intraepithelial neoplasia (LCIN, HCIN) or invasive cervical carcinoma (ICC) (Zehbe et al, 1998b, 2001a)
Summary
The objective of this study was to determine the LCR and the E6 sequences of HPV16 from north European women and to establish whether there are differences in promoter activity between the genotypes identified. No specific European LCR variant was associated with progression or higher lesion grade, while an E6 variant was found to be enriched in high-grade lesions and cancer. This E6 variant showed an amino acid change from leucine to valine at residue 83 (L83V). Of the Swedish women, the E6 sequences have previously been reported (Zehbe et al, 1998b, 2001a) and of the Finnish women the LCR sequences have previously been described (Kurvinen et al, 2000)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
