NOVEL BIOMARKERS TO TRIAGE WOMEN WITH MINOR CERVICAL LESIONS: QUANTIFYING THE COST-EFFECTIVENESS TRADEOFFS TO ENSURE FEASIBLE IMPLEMENTATION

Purpose: In Norway, primary Human papillomavirus (HPV) testing is currently not recommended for younger women (i.e., ages 25-33), yet emerging screening technologies may still allow improvements for other areas of the cervical cancer screening algorithm. We aimed to inform Norwegian decision-makers about the short-term consequences associated with the use of alternative biomarkers to triage younger women with minor cervical lesions (i.e., ASC-US/LSIL).

Methods: We expanded a previously developed probabilistic decision-tree model that projected the health and economic consequences of alternative triage strategies for women with ASC-US/LSIL through a single screening round (i.e., three years). We compared the current Norwegian guidelines (i.e., reflex HPV DNA testing with delayed HPV testing and cytology for HPV positive), to 12 candidate triage strategies that involved alternative biomarkers (i.e., reflex HPV DNA and mRNA testing, p16/Ki67 dual-staining), in terms of the number of detected precancers (i.e., CIN2+) and resource use (i.e., societal costs and colposcopy referrals). To identify efficient strategies, we calculated the incremental cost-effectiveness ratios (ICER) in terms of the additional costs per additional detected precancer for each strategy compared with the next most costly strategy. In addition, we considered feasibility by calculating the expected increase in colposcopy referrals for each efficient strategy compared with current Norwegian guidelines.

Results: Four out of the 13 strategies were considered cost-efficient (ICER range: $3,796 to $45,897 per additional detected precancer). The current guidelines detected fewer precancers and required higher costs than alternative strategies. In comparison, a strategy involving HPV mRNA testing detected 13% more precancers and reduced costs by 14%, though required 14% more colposcopy referrals. Strategies involving HPV DNA testing with immediate colposcopy for HPV positive were expected to increase precancer detection by 50%, but would also require twice as many colposcopies compared to current guidelines.

Conclusion: Novel biomarkers may be used to improve the effectiveness and efficiency of cervical cancer screening for younger women with minor cervical lesions. However, the optimal strategy depends on decision-makers willingness to accept higher resource use (either costs and/or colposcopy referrals) as well as the potential capacity constraints of Norwegian pathology laboratories. Although the use of novel biomarkers is promising, models can be expanded to investigate the long-term consequences of these strategies.