Short term persistence of human papillomavirus and risk of cervical precancer and cancer: population based cohort study
BMJ 2009; 339 doi: https://doi.org/10.1136/bmj.b2569 (Published 29 July 2009) Cite this as: BMJ 2009;339:b2569- Philip E Castle, investigator1,
- Ana Cecilia Rodríguez, medical epidemiologist3,
- Robert D Burk, professor4,
- Rolando Herrero, medical epidemiologist3,
- Sholom Wacholder, senior investigator1,
- Mario Alfaro, cytopathologist3,
- Jorge Morales, colposcopist3,
- Diego Guillen, pathologist3,
- Mark E Sherman, pathologist1,
- Diane Solomon, pathologist2,
- Mark Schiffman, senior investigator1,
- for the Proyecto Epidemiológico Guanacaste (PEG) Group
- 1Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD 20892, USA
- 2Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD 20892, USA
- 3Proyecto Epidemiológico Guanacaste, INCIENSA Foundation, San José, Costa Rica
- 4Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
- Correspondence to: P E Castle castlep{at}mail.nih.gov
- Accepted 15 April 2009
Abstract
Objective To evaluate the cumulative incidence of cervical intraepithelial neoplasia II or worse (grade II+) or cervical intraepithelial neoplasia grade III+ after short term persistence of prevalently detected carcinogenic human papillomavirus (HPV).
Design Population based cohort study.
Setting Guanacaste, Costa Rica.
Participants 2282 sexually active women actively followed after enrolment.
Main outcome measures Primary end points: three year and five year cumulative incidence of histologically confirmed cervical intraepithelial neoplasia grade II+ (n=70). Cervical specimens collected at each visit tested for more than 40 HPV genotypes. HPV 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 73, and 82 were considered the primary carcinogenic genotypes.
Results Women who tested positive for a carcinogenic HPV at enrolment and after about one year (9-21 months) (positive/positive) had a three year cumulative incidence of cervical intraepithelial neoplasia grade II+ of 17.0% (95% confidence interval 12.1% to 22.0%). Those who tested negative/positive (3.4%, 0.1% to 6.8%), positive/negative (1.2%, −0.2% to 2.5%), and negative/negative (0.5%, 0.1% to 0.9%) were at a significantly lower risk. There was little difference in the cumulative incidence of cervical intraepithelial neoplasia grade II+ between testing positive twice for any carcinogenic HPV genotype (same genotype or different genotypes) v testing positive twice for the same carcinogenic genotype (17.0% v 21.3%, respectively). Short term persistence of HPV 16 strongly predicted cervical intraepithelial neoplasia grade II+, with a three year cumulative incidence of 40.8% (26.4% to 55.1%). Similar patterns were observed for the five year cumulative incidence of grade II+ and for three year and five year cumulative incidence of grade III+.
Conclusions Short term persistence of a prevalently detected carcinogenic HPV infection, especially HPV 16, strongly predicts a subsequent diagnosis of cervical intraepithelial neoplasia II+ over the next few years.
Footnotes
We thank Allan Hildesheim for his critical review and suggestions for this manuscript. The following individuals participated in the Proyecto Epidemiológico Guanacaste (PEG) Group: M Schiffman, project officer; A Hildesheim, co-project officer; S Wacholder, statistician; M Sherman, pathologist, at the National Cancer Institute, NIH, Bethesda MD; MC Bratti, principal investigator; R Herrero, co-principal investigator; AC Rodríguez, assistant principal investigator; J Morales, colposcopist; M Alfaro, cytopathologist, and D Guillén, histopathologist, at the Costa Rican Foundation for Health Sciences, San José, Costa Rica; M Hutchinson, cytologist, at Women and Infants’ Hospital, Providence, RI; and J Schussler, senior programmer and analyst, at Information Management Services, Silver Spring, MD.
Contributors: PEC was the chief analyst and is guarantor. MS, SW, and RH designed the study. MS, AH, RH, ACR, MA, JM, and DG initiated the study. ACR and RH were responsible for the recruitment and follow-up of participants. RDB was responsible for the HPV testing. MA, DG, MES, and DS undertook cytological interpretations and histological diagnoses. PEC, MS, ACR, and SW were responsible for the statistical analysis. PEC wrote the first draft of the paper. All authors contributed to and approved the final version of the paper.
Funding: This study was supported by the National Institutes of Health (N01-CP-21081, N01-CP-33061, N01-CP-40542, N01-CP-50535, N01-CP-81023, intramural programme, CA78527 to RB). The Guanacaste cohort was partly funded by the intramural research programme of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. ACR was supported by an appointment to the senior fellowship programme at the National Institutes of Health. The programme is administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the National Institutes of Health. The sponsors had no role in the study design, data collection, data analysis, data interpretation, or the writing of the report.
Competing interests: None declared.
Ethical approval: This study was approved by the Ministry of Health of Costa Rica and the US National Cancer Institute and informed consent was given by all patients.
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