To test the significance of human papillomavirus (HPV) type 16 and HPV16 E6 variants as risk factors for viral persistence and progression to high-grade lesion, we did a nested case-control study within a cohort study of >15,000 Caucasian French women. Three groups infected with highrisk HPV were compared: (a) women with cleared infection (controls, n = 201), (b) women with persistent infection (cases, n = 87), and (c) women who progressed into highgrade lesion (cases, n = 58 A subgroup of human papillomaviruses (HPV), referred to as high-risk types, are the etiologic agents of cervical cancer (1). Among the high-risk types HPV16 is the most prevalent type in premalignant and malignant cervical lesions worldwide (2, 3). Persistence of viral infection has a key role in cervical cancer development (4, 5). HPV16 is likelier to persist (6) and to cause progression into cervical intraepithelial neoplasia (CIN) than other high-risk HPV types (7,8). Nucleic acid sequencing of HPV16 genomes has revealed the existence of numerous natural variants that differ from the original European prototype sequence (9) up to 2% in the coding region and/or up to 5% in the noncoding region (10). HPV16 variants have been classified as five major phylogenetic clusters (or lineages): European, Asian, Asian American, African, and North American. For each lineage, several subclasses have been identified (summarized in ref. 11). Interestingly, three codon sites in the HPV16 E6 open reading frame coding for amino acids 10, 14, and 83 were shown to be under selective pressure (12). Variants at these residues lead to changes from arginine to glycine or isoleucine (R10G or R10I) at codon 10, from glutamine to histidine or aspartic acid (Q14H or Q14D) at codon 14, and from leucine to valine (L83V) at codon 83. Recent studies suggest that HPV16 E6 variants are involved in determining persistence of the viral infection and the development of cervical lesions (13-20). Some of these have shown that non-European HPV16 variants are more associated with disease progression than the European variants (21, 22).By using cross-sectional analyses of several European populations, we have previously shown that within the European lineage, the L83V E6 variant harboring a nucleotide substitution at position 350 (HPV16 350G) alone or in combination with other polymorphisms is more prevalent in cervical cancer than in . This phenomenon may be explained by the fact that natural variants alter the immunogenic and/or carcinogenic properties of the virus. In this study, we have used a large French cohort to elucidate further whether HPV16 and HPV16-specific variants are predictors for persistence of infection and progression into high-grade lesion.We did a nested case-control study within a large cohort study of >15,000 Caucasian French women ages between 18 and 76 years (median = 34 years). They had been recruited between 1997 and 2003 among women who underwent their biennial or triennial routine screening in the Department of Obstetrics and Gynaecology at t...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.