COST-EFFECTIVE MANAGEMENT OF WOMEN WITH MINOR CERVICAL LESIONS: REVISITING THE APPLICATION OF HPV DNA TESTING

Purpose: New screening technologies, including assays to detect human papillomavirus (HPV), the causal agent of cervical cancer, coupled with a better understanding of the natural history of HPV and cervical disease, necessitate revisiting cervical cancer screening approaches. Within the context of the Norwegian Cervical Cancer Screening Program, we aimed to identify the optimal diagnostic work-up of women with minor cervical cytological lesions.

Method(s): We adapted an individual-based microsimulation model to reflect HPV and cervical cancer burden in Norway, including HPV infection status and persistence in progression to precancer and cancer. We projected the health and economic consequences associated with ten candidate strategies to triage women with minor cervical cytological lesions who were also high-risk HPV-positive. Candidate strategies varied by: 1) the triage test(s): HPV testing with cytology (i.e., current Norwegian guidelines), HPV testing alone with or without genotyping for HPV-16 and-18 (the two most carcinogenic types), and immediate colposcopy, and 2) the length of time between index and triage testing (i.e., ranging 6-18 months). Model outcomes included lifetime risk of cervical cancer, quality-adjusted life-years (QALYs), lifetime societal costs, and resource use (e.g., number of colposcopy referrals) associated with each strategy. We estimated the incremental cost-effectiveness ratio (ICER) to identify cost-efficient strategies.

Result(s): The candidate strategies were projected to reduce the lifetime risk of cervical cancer by 84.2% to 85.9%, and were more effective and less costly than current Norwegian guidelines. Given current willingness-to-pay recommendations in Norway of $100,000 per QALY gained, the preferred strategy involved immediate colposcopy for all high-risk HPV-positive women ($80,310 per QALY gained). This strategy was associated with a 21% increase in colposcopy referrals and a 15% increase in precancer treatments compared with current levels. Strategies involving immediate colposcopy only for women with HPV-16 or -18, and repeat HPV testing for women with non-HPV-16/-18 high-risk genotypes (at 18 or 12 months), had lower, more attractive ICERs, and required moderate increases in colposcopy and treatment referrals compared with current guidelines.

Conclusion(s): New applications of HPV testing in screening triage are likely to increase health benefit at lower costs than current Norwegian guidelines. However, the minor improvements in health benefits associated with more effective strategies require a tradeoff of increased colposcopy referrals and precancer treatments.