HEALTH-ECONOMIC EVALUATION OF HPV-BASED CERVICAL CANCER PRIMARY SCREENING COMPARED TO CYTOLOGY OR P16/KI-67 DUAL-STAINING – A DECISION-ANALYSIS FOR THE AUSTRIAN HEALTH CARE CONTEXT

Purpose:

In Austria opportunistic cervical cancer screening with annual cytology starting at age 18 years is the current standard. However, new screening tests together with risk-based screening and follow-up algorithms may have the potential to improve both, the effectiveness and the efficiency of the cervical cancer screening program. Our aim was to systematically evaluate the long-term effectiveness and cost-effectiveness of different cervical cancer primary screening strategies for the Austrian health care context.

Method(s):

A Markov-state-transition model was developed for the Austrian health care context simulating the disease including HPV-infection and different pre-invasive as well as invasive cervical cancer stages. The model was applied 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 positive test results. We used Austrian clinical, epidemiological and economic data, and test accuracy data from international meta-analyses and trials. All costs and effects were discounted at 5% annually. Index year was 2014. Predicted outcomes were reduction in cervical cancer cases and deaths, remaining life expectancy (in life years [LY]), total lifetime costs (in Euro), and the incremental cost-effectiveness ratios (ICER; in Euro/LY gained). Comprehensive sensitivity analyses were performed.

Result(s):

Within the same screening interval, HPV-based primary screening strategies are more effective (relative reduction cancer death: 56%-79% for 5-2 yearly screening intervals) compared with cytology (42%-69%) or with p16/Ki-67 testing alone (50%-76%). 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 improve efficiency. In the base-case analysis (31-43% screening adherence in women below 60 years of age), optimal balance between benefits and costs achieved biennial HPV-testing (with cytology triage of HPV-positive women) at the age of 30 years and biennial cytology (with p16/Ki-67-triage of women with ASCUS/LSIL) at younger age with an ICER of 43,700 Euro/LY gained. In sensitivity analyses results were sensitive with regard to HPV-test cost, cytology test accuracy, screening adherence rate and annual discount rate.

Conclusion(s):

Based on our results, biennial primary HPV screening with cytology triage in women age 30 years and older and biennial cytology with p16/Ki-67-triage in younger women can be considered as a cost-effective screening option for the Austrian context.