American Journal of Epidemiology Advance Access originally published online on May 15, 2008
American Journal of Epidemiology 2008 168(2):123-137; doi:10.1093/aje/kwn036
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Persistent Human Papillomavirus Infection and Cervical Neoplasia: A Systematic Review and Meta-Analysis
1 Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD
2 GlaxoSmithKline Biologicals, Rixensart, Belgium
3 Worldwide Epidemiology, GlaxoSmithKline, Greenford, United Kingdom
4 Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC
Correspondence to Dr. Jill Koshiol, National Cancer Institute, 6120 Executive Blvd., MSC 7236, Bethesda, MD 20892-7236 (e-mail: koshiolj{at}mail.nih.gov) or Dr. Jennifer S. Smith, CB 7435, McGavran-Greenberg Building, School of Public Health, University of North Carolina–Chapel Hill, Chapel Hill, NC 27599-7435 (e-mail: jennifers{at}unc.edu).
Received for publication May 8, 2007. Accepted for publication October 29, 2007.
Detection of persistent cervical carcinogenic human papillomavirus (HPV) DNA is used as a marker for cervical cancer risk in clinical trials. The authors performed a systematic review and meta-analysis of the association between persistent HPV DNA and high-grade cervical intraepithelial neoplasia (CIN2-3), high-grade squamous intraepithelial lesions (HSIL), and invasive cervical cancer (together designated CIN2-3/HSIL+) to evaluate the robustness of HPV persistence for clinical use. MEDLINE and Current Contents were searched through January 30, 2006. Relative risks (RRs) were stratified by HPV comparison group. Of 2,035 abstracts, 41 studies were eligible for inclusion in the meta-analysis. Over 22,500 women were included in calculation of RRs for persistent HPV DNA detection and cervical neoplasia. RRs ranged from 1.3 (95% confidence interval: 1.1, 1.5) to 813.0 (95% confidence interval: 168.2, 3,229.2) for CIN2-3/HSIL+ versus <CIN2-3/HSIL+; 92% of RRs were above 3.0. Longer durations of infection (>12 months), wider testing intervals, CIN2-3/HSIL+, and use of an HPV-negative reference group were consistently associated with higher RRs. Thus, HPV persistence was consistently and strongly associated with CIN2-3/HSIL+, despite wide variation in definitions and study methods. The magnitude of association varied by duration of persistence and testing interval. Precise definition and standardization of HPV testing, sampling procedure, and test interval are needed for reliable clinical testing. These findings validate HPV persistence as a clinical marker and endpoint.
human papillomavirus 16; human papillomavirus 18; longitudinal studies; papillomavirus infections; uterine cervical neoplasms
Abbreviations: ASCUS, atypical squamous cells of undetermined significance; CI, confidence interval; CIN, cervical intraepithelial neoplasia; HPV, human papillomavirus; HSIL, high-grade squamous intraepithelial lesions; LSIL, low-grade squamous intraepithelial lesions; PCR, polymerase chain reaction; SIL, squamous intraepithelial lesions
Editor's note: An invited commentary on this article appears on page 134, and the authors' response appears on page 145.
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  P. E. Castle Invited Commentary: Is Monitoring of Human Papillomavirus Infection for Viral Persistence Ready for Use in Cervical Cancer Screening? Am. J. Epidemiol., July 15, 2008; 168(2): 138 - 144. [Abstract] [Full Text] [PDF]
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J. Koshiol, C. Poole, H. Chu, J. M. Pimenta, L. Lindsay, D. Jenkins, and J. S. Smith The Authors Respond to "HPV Persistence and Cervical Cancer Screening" Am. J. Epidemiol., July 15, 2008; 168(2): 145 - 148. [Full Text] [PDF]
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