Journal of the National Cancer Institute Advance Access published online on March 25, 2008
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djn044
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Published by Oxford University Press 2008.
BRIEF COMMUNICATION |
Rapid Clearance of Human Papillomavirus and Implications for Clinical Focus on Persistent Infections
Affiliations of authors: Divisions of Cancer Epidemiology and Genetics (ACR, MS, SW, AH, PEC) and Cancer Prevention (DS), National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD; Proyecto Epidemiológico Guanacaste, INCIENSA Foundation, San José, Costa Rica (ACR, RH); Albert Einstein Cancer Center, Albert Einstein College of Medicine, The Bronx, NY (RB)
Correspondence to: Ana Cecilia Rodríguez, MD, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, EPS, Rm 5032, Rockville, MD 20852 (e-mail: rodrigac{at}mail.nih.gov).
Health professionals and the public need to understand the natural history of human papillomavirus (HPV) infections of the cervix to best use the information provided by new molecular screening tests. We investigated outcomes of 800 carcinogenic HPV infections detected in 599 women at enrollment into a population-based cohort (Guanacaste, Costa Rica). For individual infections, we calculated cumulative proportions of three outcomes (viral clearance, persistence without cervical intraepithelial neoplasia grade 2 or worse [CIN2+], or persistence with new diagnosis of CIN2+) at successive 6-month time points for the first 30 months of follow-up. Cervical specimens were tested for carcinogenic HPV genotypes using an L1 degenerate-primer polymerase chain reaction method. Infections typically cleared rapidly, with 67% (95% confidence interval [CI] = 63% to 70%) clearing by 12 months. However, among infections that persisted at least 12 months, the risk of CIN2+ diagnosis by 30 months was 21% (95% CI = 15% to 28%). The risk of CIN2+ diagnosis was highest among women younger than 30 years with HPV-16 infections that persisted for at least 12 months (53%; 95% CI = 29% to 76%). These findings suggest that the medical community should emphasize persistence of cervical HPV infection, not single-time detection of HPV, in management strategies and health messages.
| CONTEXT AND CAVEATS Prior knowledge Cervical infections with carcinogenic human papillomavirus (HPV) types are common, but most infections are transient and do not increase a woman’s risk for cervical cancer. However, if the infection is persistent, the risk of cervical cancer is increased substantially. Understanding the natural history of HPV infection is important as molecular tests for HPV come into widespread use. Study design Longitudinal analysis of data from women enrolled in a population-based cohort in Guanacaste, Costa Rica, and screened regularly for HPV and cervical cytology. Viral clearance, viral persistence without cervical intraepithelial neoplasia grade 2 or worse (CIN2+), and viral persistence with CIN2+ were assessed over time for carcinogenic HPV infections detected at enrollment. Contributions Most infections cleared rapidly, with two-thirds clearing by 12 months. Among infections that persisted for at least 12 months, 21% were associated with a CIN2+ diagnosis by 30 months. The risk was highest in women younger than 30 years with persistent HPV-16 infection, with 53% of such infections leading to a diagnosis of CIN2+ by 30 months. Implications Patients with normal cytology but with cervical infection with carcinogenic HPV should be managed with watchful waiting because of the high likelihood that their infection will clear. Persistent infection calls for more active treatment. Limitations The intensive screening of women in this study could have led to overestimates of CIN2+ lesions because these have a relatively high regression rate. Similarly, the clearance estimates could have been affected by the screening intervals, with clearance likely occurring faster than could be measured.
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The Guanacaste cohort (design and conduct of the study, sample collection, management, analysis and interpretation of the data) for the enrollment and follow-up phases was supported by the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. A. C. Rodríguez was supported by an appointment to the Senior Fellowship Program at the National Institutes of Health for analysis and manuscript preparation. The program is administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the National Institutes of Health.
The authors take full responsibility for the design and conduct of the study, the analysis and interpretation of the data, the content of the manuscript, and the decision to submit it for publication.
Manuscript received August 27, 2007; revised January 17, 2008; accepted February 1, 2008.
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J Natl Cancer Inst 2008 100: 447.
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