PROSPECTIVE SEROEPIDEMIOLOGIC STUDY OF HUMAN-PAPILLOMAVIRUS INFECTIONAS A RISK FACTOR FOR INVASIVE CERVICAL-CANCER

Background: Major risk factors for invasive cervical cancer include in fection with human papillomavirus (HPV), infection with other sexually transmitted pathogens (e.g., Chlamydia trachomatis), and smoking. Sin ce exposures to these risk factors can be related, the contribution of any single factor to cervical carcinogenesis has been difficult to as sess. We conducted a prospective study to define the role of HPV infec tion in cervical carcinogenesis, with invasive cancer as an end point. Methods: A nested case-control study within a joint cohort of 700 000 Nordic subjects was performed, The 182 women who developed invasive c ervical cancer during a mean follow-up of 5 years were matched with 53 8 control women on the basis of age and time of enrollment. Serum samp les taken at enrollment were analyzed for evidence of tobacco use (i.e ., cotinine levels); for antibodies against HPV types 16, 18, and 33; and for antibodies against C. trachomatis. Relative risks (RRs) were e stimated by use of conditional logistic regression, Results: Presence of antibodies against HPV in serum (seropositivity) was associated wit h an increased risk of cervical cancer, and adjustment for smoking and for C. trachomatis seropositivity did not affect this finding (RR = 2 .4; 95% confidence interval [CI] = 1.6-3.7), HPV16 seropositivity was associated primarily with an increased risk of squamous cell carcinoma (RR = 3.2; 95% CI = 1.7-6.2). In contrast, risk associated with HPV18 seropositivity tended to be higher for cervical adenocarcinoma (RR = 3.4; 95% CI = 0.8-14.9). In populations with a low prevalence of antib odies against C trachomatis, the HPV16-associated risk of cervical can cer was very high (RR = 11.8; 95% CI = 3.7-37.0); in contrast, in popu lations with a high prevalence of antibodies against C. trachomatis, n o excess risk was found, Conclusion: Past infection with HPV16 increas es the risk of invasive cervical squamous cell carcinoma, most clearly seen in populations with a low prevalence of sexually transmitted dis eases.