A Long-term Prospective Study of Type-Specific Human Papillomavirus Infection and Risk of Cervical Neoplasia Among 20,000 Women in the Portland Kaiser Cohort Study

Background: Human papillomavirus (HPV) DNA testing is more sensitive than cytology for detection of cervical intraepithelial neoplasia grade 3 and cancer (>= CIN3). Adding HPV testing to cytology is recommended for women >= 30 but long-term prospective studies of HPV testing are rare. Methods: Beginning in 1989-1990, similar to 20,000 women in a prepaid health maintenance organization (median age 34) were followed passively by recommended annual cytology. We tested archived cervicovaginal lavage specimens collected at enrollment, primarily by MY09-MY11 PCR-based methods, for carcinogenic HPV types. We calculated positive and negative predictive values for the entire study period, and Kaplan-Meier estimates of cumulative probability for >= CIN3, up to 18 years of follow-up. Results: We observed 47 cases of invasive cervical cancer during the study period, and 156 cases of CIN3. Predictive values and Kaplan-Meier analyses yielded the same conclusions. In women 30 and older, the reassurance against >= CIN3 following a single negative HPV test was long-lasting (cumulative probability = 0.7% during follow-up). In this age group, a single HPV test (positive vs. negative, hazard ratio of 8.5, 95% CI = 4.8-15.1) provided greater long-term risk stratification than a single cytologic result (abnormal vs. normal, HR = 2.9, 95% CI = 1.2-6.6). The risk for >= CIN3 was higher for HPV16 than for the average of the other carcinogenic types (hazard ratio = 2.7). Conclusion and Impact: The data from this cohort study show the long-term predictive value of HPV testing, particularly in women >= 30, and a possible role for distinguishing particularly carcinogenic types like HPV16. Cancer Epidemiol Biomarkers Prev; 20(7); 1398-409. (C)2011 AACR.