ABSTRACT The HPV vaccine is highly effective in clinical trials, with an absolute risk of persistent (6+ months) infection with vaccine-type high-risk HPV of only 1.4% among vaccinated women. As prevalence of HPV infection decreases, the risk of false positive cervical cancer screening results increases. However, current cervical cancer screening guidelines do not differentiate between vaccinated and unvaccinated women. Data cannot be extrapolated from other countries with different HPV vaccination coverage, as cross-protection against non- vaccine type HPV infection varies by population vaccination rates, and are likely to affect screening test performance. Major challenges in development of new U.S. guidelines are anticipated for the following reasons: 1) large U.S. population-based data on HPV infection rates and cervical cancer screening test statistics are currently not available, and likely vary by regional vaccination rates; 2) most studies evaluating cervical cancer screening results in vaccinated women do not differentiate between those who have received only 1 dose of the vaccine and those who have completed the 2-3 dose series; 3) few studies have evaluated differences in outcomes by age at HPV vaccine initiation or interval between doses. The overarching aim of the proposed research is to determine an optimal cervical cancer screening strategy for women vaccinated against HPV. The objectives of this pilot research are to 1) determine if the prevalence of cervical dysplasia has decreased with HPV vaccination and resultantly changed the PPV of cervical cancer screening tests, and 2) determine if cervical cancer screening test performance varies by age at HPV vaccine initiation, number of doses, or interval between HPV vaccine doses. Aim1: Determine if the decrease in prevalence of cervical dysplasia among vaccinated women has resulted in a decrease in the positive predictive value of cervical cancer screening tests. A cross-sectional study will be conducted to compare cervical cancer screening and diagnostic test results among HPV-vaccinated and unvaccinated women. Positive predictive values for positive HPV tests and abnormal cytology results to predict high-grade dysplasia will be compared by HPV vaccination status. Aim2: Determine if cervical cancer screening test accuracy varies by age at vaccine initiation, number of doses received, and/or interval between doses. The positive predictive value of positive HPV tests and abnormal Pap test results among vaccinated women will be compared by the number of vaccine doses received (1 vs. 2+), age at vaccine initiation, and interval between doses using logistic regression.