Under which realistic circumstances is <scp>hrHPV</scp> self‐sampling increasing cervical screening effectiveness in a partly vaccinated population? A modelling study

High-risk Human Papillomavirus self-sampling can increase attendance rates for screening. However, observed lower sensitivity and loss to follow-up of self-sampling could reduce programme effectiveness when attenders of clinician-collected sampling switch to self-sampling. We determined the tipping point for effectiveness (based on life years gained [LYG]) of self-sampling and the consequences for cost-effectiveness, taking into account waste by comparing full opt-out (no waste) to no opt-out (waste from unused self-sampling kits). We used the STDSIM-MISCAN-Cervix microsimulation model to simulate a population of Dutch women born in 2000 (50% vaccinated [sensitivity analysis: 0-100%], 70% screening attendance [sensitivity analysis: 60-80%]). Self-sampling deployment strategies (e.g., direct-mail) were varied by the percentage of original attenders switching to self-sampling and the percentage of new attendance from non-attenders. Main outcome measures were LYG and cost-effectiveness (cost per quality adjusted [QA] LY gained) compared to the current programme. We found that if self-sampling does not reach non-attenders, life years cannot be gained. When reaching 10% or 30% of non-attenders, the tipping point lies at ≤40% and ≤100% switchers to maintain effectiveness, respectively (+4 LYG, +10 LYG). Scenarios were cost-effective (<€50,000/QALY gained) if at least 10% of non-attenders were reached. Full opt-out improved cost-effectiveness substantially. So, in a partly vaccinated population, self-sampling deployment strategies need to reach at least 10% of non-attenders to maintain programme effectiveness and cost-effectiveness. A well-functioning opt-out system further improves cost-effectiveness by preventing waste.