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Human Papillomavirus and Long-term Oral Contraceptive Use Increase the Risk of Adenocarcinoma in Situ of the Cervix¹

Programs in Epidemiology [M. M. M., J. R. D., S. M. S.] Cancer Biology [K. S., J. J. C., G. C. W., J. K. M., P. P., D. A. G.], Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; Departments of Epidemiology [J. R. D., S. M. S., C. W. C.] and Biostatistics [B. M.], School of Public Health and Community Medicine, University of Washington, Seattle, Washington 98195; and Departments of Microbiology [D. A. G.] and Pathology [J. K. M., P. P.], School of Medicine, University of Washington, Seattle, Washington 98195

We examined United States Surveillance, Epidemiology, and End Results incidence data and conducted a population-based case-control study to examine the role of human papillomavirus (HPV) and oral contraceptive (OC) use in the etiology of adenocarcinoma in situ of the cervix (ACIS). One hundred and fifty women diagnosed with ACIS and 651 randomly selected control women completed in-person interviews. The presence of HPV DNA in archival ACIS specimens was determined by E6 and L1 consensus PCR. Serum samples from case and control subjects were collected at interview, and antibodies to HPV-16 L1 and HPV-18 L1 were detected by virus-like particle capture assays. The overall prevalence of HPV DNA was 86.6%, with 39.0% positive for HPV-16 DNA, 52.4% positive for HPV-18 DNA, and 13.4% positive for more than one HPV type. The age-adjusted relative risk of ACIS associated with HPV-18 seropositivity was 3.3 (95% confidence interval 2.2–4.9). No increased risk was associated with antibodies to HPV-16 L1. Among women born after 1945, the relative risk increased with duration of OC use, with the highest risk for 12 or more years of use (odds ratio, 5.5; 95% confidence interval, 2.1–14.6) relative to nonusers. The detection of HPV DNA in 86.6% of ACIS and the strong association of ACIS with HPV-18 L1 seropositivity underscore the importance of HPV, particularly HPV-18, in the etiology of ACIS. In addition, long-term OC use may contribute to the pathogenesis of these tumors in some women.

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