A study of the risks of CIN3+ detection after multiple rounds of HPV testing: Results of the 15-year cervical cancer screening experience at Kaiser Permanente Northern California.

Many countries are transitioning to HPV testing for cervical cancer screening, despite a lack of long-term experience. To anticipate multi-round screening performance, we analyzed 15-year HPV testing results at Kaiser Permanente Northern California (KPNC). We evaluated HPV test result patterns among women aged 30-64 undergoing triennial HPV/cytology cotesting at KPNC during 2003-2018. We calculated incidence rates and proportion of CIN3+ diagnoses associated with the most frequent HPV testing patterns overall and stratified by age. From 2003 to 2018, a total of 1,361,581 women had a valid HPV test result, and 7,087 were diagnosed with CIN3+. Incidence rates of CIN3+ after HPV positivity were lowest when HPV detection was new and highest in women with prevalent infections (770 vs. 13,910/100,000 person-years). Repeat test negativity reduced subsequent incidence rates of CIN3+ to extremely low levels (18/100,000 person-years following four consecutive negative results). For mixed patterns of positivity/negativity, the recency and frequency of positive tests were associated with increased rates of CIN3+ diagnosis. Most CIN3+ cases (76%) were diagnosed in women who were positive at baseline (the first known positive HPV result); 16% were attributed to apparent newly detected infections and 3% to possible reappearing infections. These results corroborate previous findings that current HPV positivity, particularly when prevalent rather than new, is associated with the highest rates of CIN3+. In a screening program implementing HPV testing, most CIN3+ is detected at the first HPV positive test.