Influence of human papillomavirus type 16 (HPV-16) E2 polymorphism on quantification of HPV-16 episomal and integrated DNA in cervicovaginal lavages from women with cervical intraepithelial neoplasia
1 Laboratoire de Virologie Moléculaire, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada 2 Department of Epidemiology, Biostatistics and Occupational Health Medicine, McGill University, Montreal, Québec, Canada 3 Department of Obstetrics and Gyneco...
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| Published in: | Journal of general virology Vol. 89; no. 7; pp. 1716 - 1728 |
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| Main Authors: | , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
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Soc General Microbiol
01-07-2008
Society for General Microbiology |
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| Online Access: | Get full text |
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| Summary: | 1 Laboratoire de Virologie Moléculaire, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada
2 Department of Epidemiology, Biostatistics and Occupational Health Medicine, McGill University, Montreal, Québec, Canada
3 Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada
4 Department of Medicine, Sunny Brook Health Science Centre, University of Toronto, Toronto, Ontario, Canada
5 Department of Pathology and Obstetrics & Gynecology, The Sir Mortimer B. Davis-Jewish General Hospital and McGill University, Québec, Canada
6 Departments of Oncology, Division of Epidemiology, McGill University, Montreal, Québec, Canada
7 Département de Microbiologie et Immunologie, Université de Montréal, Montréal, Québec, Canada
Correspondence François Coutlée francois.coutlee{at}ssss.gouv.qc.ca
Integrated human papillomavirus type 16 (HPV-16) viral loads are currently estimated by quantification with real-time PCR of HPV-16 E6 (RT-E6 and HPV-16 PG) and E2 (RT-E2-1) DNA. We assessed the influence of HPV-16 E2 polymorphism on quantification of integrated HPV-16 DNA in anogenital specimens. HPV-16 E2 was sequenced from 135 isolates (123 from European and 12 from non-European lineages). An assay targeting conserved HPV-16 E2 sequences (RT-E2-2) was optimized and applied with RT-E6 and RT-E2-1 on 139 HPV-16-positive cervicovaginal lavages collected from 74 women [58 human immunodeficiency virus (HIV)-seropositive and 16 HIV-seronegative]. Ratios of HPV-16 copies measured with RT-E2-2 and RT-E2-1 obtained with African 2 (median=3.23, range=1.92–3.49) or Asian–American (median=3.78, range=1.47–37) isolates were greater than those obtained with European isolates (median=1.02, range=0.64–1.80; P <0.02 for each comparison). The distribution of HPV-16 E2 copies measured in 139 samples with RT-E2-2 (median=6150) and RT-E2-1 (median=8960) were different ( P <0.0001). The risk of high-grade cervical intraepithelial neoplasia (CIN-2,3) compared with women without CIN was increased with higher HPV-16 total [odds ratio (OR)=2.17, 95 % confidence interval (CI)=1.11–4.23], episomal (OR=2.14, 95 % CI=1.09–4.19), but not for HPV-16 integrated viral load (OR=1.71, 95 % CI=0.90–3.26), after controlling for age, race, CD4 count, HIV and HPV-16 polymorphism. The proportion of samples with an E6/E2 ratio >2 in women without squamous intraepithelial lesion (7 of 35) was similar to that of women with CIN-2,3 (5 of 11, P =0.24) or CIN-1 (5 of 14, P =0.50). HPV-16 E2 polymorphism was a significant factor that influenced measures of HPV-16 integrated viral load.
Members listed in Acknowledgements. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 0022-1317 1465-2099 |
| DOI: | 10.1099/vir.0.83579-0 |