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

Abstract

ObjectivesIn 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.MethodsWe 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.ResultsFor 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.ConclusionsWe 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.HighlightsPeople 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.

Keywords: cervical cancer; cervical screening; human papillomavirus (HPV) vaccination; microsimulation.

Figure 1

The efficiency frontier of different human papillomavirus (HPV)–based screening strategies in the prevaccinated population. The orange crosses and line represent the efficient frontier. The proposed 9 lifetime HPV tests (orange circle) are on the frontier with an incremental harms–benefits ratio of 4,721 harms per cancer prevented. The cytology-based strategy (gray circle) is clearly shown to be dominated by alternative HPV-based screening strategies. Combined harms = screening tests + 10 × colposcopy referrals. IHBR, incremental harms–benefits ratio.

Figure 2

Effectiveness of all evaluated human papillomavirus (HPV)–based screening strategies for preventing cervical cancer incidence in different subgroups of vaccinated cohorts. The combined, unstratified results are displayed in blue with the unvaccinated individuals from these cohorts in red and the vaccinated subgroup in green. Squares represent the optimal strategy using the IHBR threshold of 4,721. The blue circles represent the potential outcome of the optimal unstratified strategy (blue square) in either of the 2 stratified subpopulations. Combined harms = screening tests + 10 × colposcopy referrals. IHBR, incremental harms–benefits ratio. Strategy names should be read as (number of lifetime screens [including optional screens)] – (triage protocol) − (start age, end age).