IMPROVING CERVICAL CANCER PRIMARY SCREENING AND DIAGNOSTIC FOLLOW-UP IN AUSTRIA – A DECISION-ANALYTIC BENEFIT-HARM ANALYSIS

Purpose:

In Austria, current opportunistic cervical cancer screening program includes annual Pap cytology for women as of age 18 years. However, new primary screening tests with increased test-sensitivity in combination with risk-based follow-up algorithms may improve the trade-off between benefits and overtreatment. Our aim was to systematically evaluate the benefit-harm balance of different cervical cancer primary screening strategies for the Austrian context.

Method(s):

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 (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 and epidemiological data, as well as test accuracy data from international meta-analyses and trials were used. Predicted outcomes were reduction in cervical cancer incidence, -mortality, overtreatment (defined as conization with histological diagnosis of no lesion or a lesion grade CIN1), and the incremental harm-benefit ratios (IHBR) measured in numbers of overtreatment per additional prevented cervical cancer death. Comprehensive sensitivity analyses were performed.

Result(s):

Based on our results, 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/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 below 60 years of age), biennial HPV+cytology cotesting seemed to be the optimal screening strategy (IHBR: 45 unnecessary conizations per additional prevented cancer death). Annual screening strategies resulted in much higher IHBRs (131-355 unnecessary conizations per additional prevented cancer death). Based on the IHBRs, the screening interval may be extended to 3 years in populations with screening adherence of 40%-60% and to 5 years in populations with higher adherence rate. The age for screening initiation could be extended from 18 to 24 years without significant loss in effectiveness, but with reduced overtreatment.

Conclusion(s):

Based on our benefit-harm analysis, HPV-based screening in women of the age 30 years or older 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. Screening should be initiated in women of the age 20-24 years.