Primary cervical cancer screening may be optimized using new risk-based screening and follow-up algorithms with improved benefit-harm trade-offs. Our aim was to systematically evaluate and compare the benefit-harm balance of different cervical cancer primary screening strategies for the Austrian context.
We used a validated Markov-state-transition model calibrated to the Austrian epidemiological setting and clinical context of the disease to evaluate different screening strategies that differ by primary screening test (including cytology, p16/Ki-67-dual stain, and HPV-testing alone or in combinations), screening interval, age, and specific follow-up algorithms for women with positive test results. Austrian clinical, epidemiological and economic data, as well as test accuracy data from international meta-analyses and trials were incorporated. Predicted outcomes are reduction in cervical cancer incidence and mortality, remaining life expectancy, overtreatment (defined as conization with histological diagnosis of no lesion or a lesion grade CIN 1), and the incremental harm-benefit ratios (IHBR) measured in numbers of overtreatment per additional prevented cervical cancer death. Comprehensive sensitivity analyses were performed.
Based on our results, within the same screening interval, HPV-based primary screening strategies are more effective compared with cytology or with p16/Ki-67-testing alone. Adopting risk-based follow-up algorithms including p16/Ki-67 triage for women with ASCUS or LSIL and colposcopy referral for women with HSIL or p16/Ki-67-positivity can reduce overtreatment. In the base-case analysis (31-43% screening adherence in women age 20-59 years), the IHBRs were 19 (5-yearly cytology+p16/Ki-67-triage), 31 (3-yearly cytology+p16/Ki-67-triage), 40 (3-yearly HPV+cytology cotesting), 45 (2-yearly HPV+ cytology cotesting), 131 (annual cytology +p16/Ki-67-triage), and 355 (annual p16/Ki-67 testing alone) unnecessary conizations per prevented cancer death. In populations with screening adherence below 40% biennial HPV+cytology cotesting may be performed. Depending on screening adherence rates, the screening interval may be extended to 3 years (40%-60% adherence) or to 5 years (≥ 60% adherence). The age for screening initiation could be extended from 18 to 24 years without significant loss in effectiveness, but with reduced overtreatments.
Based on our benefit-harm analysis, HPV-based screening in women at age 30 years and cytology in younger women at screening intervals of at least 2 years incorporating a risk-based follow-up algorithm can be recommended for the Austrian screening setting.