Estimating the direct effect of human papillomavirus vaccination on the lifetime risk of screen‐detected cervical precancer

Abstract

Birth cohorts vaccinated against human papillomavirus (HPV) are now entering cervical cancer screening. Assessment of (pre)cancer (CIN3+) risk is needed to assess the residual screening need in vaccinated women. We estimated the lifetime (screen-detected) CIN3+ risk under five-yearly primary HPV screening between age 30 and 60, using HPV genotyping and histology data of 21,287 women participating in a screening trial with two HPV-based screening rounds, 5 years apart. The maximum follow-up after an HPV-positive test was 9 years. We re-estimated the CIN3+ risk after projecting direct vaccine efficacy for the bivalent and the nonavalent HPV vaccines, assuming lifelong protection. The lifetime CIN3+ risk was 4.1% (95% confidence interval 3.5-4.9) and declined by 53.5% and 70.5% after bivalent vaccination without and with cross-protection, respectively, translating into a residual lifetime CIN3+ risk of 1.9% (1.4-2.4) and 1.2% (0.9-1.5). The CIN3+ risk declined by 88.5% after nonavalent vaccination, translating into a residual lifetime CIN3+ risk of 0.5% (0.2-0.7). The latter risk increased to 1.6% when vaccine protection only lasted until the first screening round at age 30. Among HPV-positive women with abnormal adjunct cytology, the nine-year CIN3+ risk was 16.9% (8.7-32.4) after nonavalent vaccination. In conclusion, HPV vaccination will lead to a strong decline in the lifetime CIN3+ risk and the remaining absolute CIN3+ risk will be very low. Primary HPV testing combined with adjunct cytology at five-year intervals still seems feasible even after nonavalent vaccination, although unlikely to be cost-effective. Our results support a de-intensification of screening programs in settings with high vaccination coverage. K E Y W O R D S cervical intraepithelial neoplasia (CIN), HPV-based screening, human papillomavirus (HPV), lifetime risk, prophylactic vaccination Abbreviations: 2/4/9vHPV, bivalent/quadrivalent/nonavalent HPV vaccine; CI, confidence interval; CIN (2/3+), cervical intraepithelial neoplasia (grade 2/3 or worse); HPV, human papillomavirus; PALGA, nationwide network and registry of histo-and cytopathology in the Netherlands, Dutch for "Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief"; POBASCAM, Population-based Screening Study Amsterdam.

Cervical cancer screening guidelines and screening practices in 11 countries: A systematic literature review

“…While the 2019 ASCCP guidelines address the management and follow-up of cervical screening abnormalities, a need also exists for changes in guideline recommendations for routine primary cervical cancer screening, as the lifetime CIN3+ risk and the performance of current cervical cancer screening will decline due to vaccination. De-intensification of screening programs, starting at an older age and with longer screening intervals, is suggested in settings with high vaccination coverage ( Drolet et al, 2019 Aug 10 , Inturrisi et al, 2021 ). However, studies providing robust data to inform future decisions on the modification of cervical cancer screening programs are needed.…”

An Updated Analysis of the Impact of HPV Vaccination Based on Long-term Effectiveness in the Netherlands

“…Higher efficacy rates were presented in the end-of-study analysis PATRICIA trial, reaching over 90% against all CIN3+, irrespective of HPV type and age group [ 8 ]. Differences between efficacy and long-term effectiveness rates suggest even higher vaccine effectiveness in the real-world setting, although these variations could also be ascribed to a different surveillance strategy in a trial-based study compared to the real-world situation [ 32 ].…”

Projected health and economic effects of nonavalent versus bivalent human papillomavirus vaccination in preadolescence in the Netherlands

“…To es mate the detec on rate of high-grade precancerous lesions through HPV-based screening, we analysed the outcomes of the Dutch cervical screening programme between 2017-2019. The expected number of colposcopies per screening round was computed from the expected number of cervical intraepithelial neoplasia (CIN) grade 2/3 diagnoses by mul plying the la er with the number of colposcopies needed to detect one precancerous lesion, stra fied by screening round [20]. The age-specific incidence and survival rates for cervical cancer and the other HPV-related cancers were es mated from Netherlands Cancer Registry data over the years 2015-2019.…”