Optimizing the Harms and Benefits of Cervical Screening in a Partially Vaccinated Population in Ontario, Canada: A Modeling Study

Objectives In Ontario, Canada, the first cohorts who were offered school-based human papillomavirus (HPV) vaccination are now eligible for cervical screening. We determined which screening strategies for these populations would result in optimal harms–benefits ratios of screening. Methods We used the hybrid microsimulation model STDSIM- MISCAN-Cervix to determine the harms and cancers prevented of 309 different primary HPV screening strategies, varying by screening ages and triage methods. In addition, we performed an unstratified (i.e., uniform screening protocols) and stratified (i.e., screening protocols by vaccination status) analysis. Harms induced were quantified as a weighted combination of the number of primary HPV-based screens and colposcopy referrals at 1:10. A harms–benefit acceptability threshold of number of harms induced for each cancer prevented was set at the estimated ratio under current screening recommendations in unvaccinated cohorts in Ontario. Results For the unstratified scenario, 5 lifetime screens with HPV16/18 genotyping was optimal. For the stratified scenario, the optimal scenario was 3 lifetime screens with HPV16/18/31/33/45/52/58 genotyping for vaccinated individuals versus 6 lifetime screens with HPV16/18 genotyping for unvaccinated individuals. Conclusions We determined the optimal cervical screening strategy in Ontario over the next decades. To maintain an optimal harms–benefits balance of screening, the Ontario Cervical Screening Program could adjust screening recommendations in the future to reduce the number of lifetime screens and extend screening intervals to account for vaccinated cohorts. Stratified screening by vaccination status could further improve this balance on an individual level. Highlights People in cohorts who were offered HPV vaccination as part of Ontario’s school-based program may achieve a better harms–benefits balance if cervical screening recommendations are updated to a less intensive protocol in future. This holds for the cohorts as a whole (i.e., unstratified screening) as well as for both vaccinated and unvaccinated individuals in these cohorts. Instead of using a cost-effectiveness threshold, it is possible to determine optimal screening protocols by calculating an acceptability threshold using alternative harms–benefits measures based on existing policy. Using univariate harms measures such as primary HPV screening tests or colposcopies per 1,000 people can yield biases in optimizing cervical screening programs. Alternatively, combining both primary screens and colposcopy referrals could provide a more accurate harms measure and result in optimal strategies with a better balance between harms and benefits.