Abstrak: 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.

Abstrak: Persistent cervical infections by approximately 15 carcinogenic genotypes of human papillomavirus (HPV) cause virtually all cases of cervical cancer and its immediate precancerous precursor, cervical intraepithelial neoplasia grade 3 or carcinoma in situ. As is shown in a meta-analysis by Koshiol et al. (Am J Epidemiol 2008;168:123–137), detection of carcinogenic HPV viral persistence could be used to identify women at the greatest risk of cervical precancer. Specifically, women who have carcinogenic HPV infection that persists for at least 1 year versus those whose infections clear are at significantly elevated risk of having or developing cervical precancer. However, before detection of HPV persistence can be used in cervical cancer screening, several considerations need to be addressed: 1) validation and Food and Drug Administration approval of a reliable HPV genotyping test, 2) rational clinical algorithms based on risk of precancer and cancer for the clinical management of HPV persistence, 3) clinician and patient acceptability of monitoring of HPV infections (including not responding excessively to the first positive HPV test and waiting 1–2 years for infections to either persist or resolve), and 4) patient compliance with recommended follow-up. Investigators will need to address these and other key issues in order to realize the potential utility of HPV viral monitoring for improving the accuracy of cervical cancer screening.