Long-term HPV type-specific risks of high-grade cervical intraepithelial lesions: A 14-year follow-up of a randomized primary HPV screening trial

Quantitative knowledge of the long-term human papillomavirus (HPV) type-specific risks for high-grade cervical intraepithelial neoplasias Grades 2 and 3 (CIN2 and CIN3) is useful for estimating the effect of elimination of specific HPV types and clinical benefits of screening for specific HPV types. We estimated HPV type-specific risks for CIN2 and CIN3 using a randomized primary HPV screening trial followed up for 14.6 years using comprehensive, nationwide registers. Poisson regression estimated cumulative incidences, population attributable proportions (PAR) and incidence rate ratios (IRRs) of high-grade lesions by baseline HPV type, with censoring at date of first CIN2/3 or last registered cytology. Multivariate analysis adjusted for coinfections. IRRs were highest during the first screening round, but continued to be high throughout follow-up (IRRs for CIN3 associated with high-risk (HR) HPV positivity were 226.9, 49.3, 17.7 and 10.3 during the first, second and third screening round and for >9 years of follow-up, respectively). Increased long-term risks were found particularly for HPV Types 16, 18 and 31 and for CIN3+ risks. HPV16/18/31/33 had 14-year cumulative incidences for CIN3+ above 28%, HPV35/45/52/58 had 14 year risks between 14% and 18% and HPV39/51/56/59/66/68 had risks <10%. HPV16 contributed to the greatest proportion of CIN2+ (first round PAR 36%), followed by Types 31, 52, 45 and 58 (7-11%). HPV16/18/31/33/45/52/58 together contributed 73.9% of CIN2+ lesions and all HR types contributed 86.9%. In summary, we found substantial differences in risks for CIN2 and CIN3 between different oncogenic HPV types. These differences may be relevant for both clinical management and design of preventive strategies.