Choosing wisely: a model-based analysis evaluating the trade-offs in cancer benefit and diagnostic referrals among alternative HPV testing strategies in Norway

Background: Forthcoming cervical cancer screening strategies involving human papillomavirus (HPV) testing for women not vaccinated against HPV infections may increase colposcopy referral rates. We quantified health and resource trade-offs associated with alternative HPV-based algorithms to inform decision-makers when choosing between candidate algorithms. Methods: We used a mathematical simulation model of HPV-induced cervical carcinogenesis in Norway. We compared the current cytology-based strategy to alternative strategies that varied by the switching age to primary HPV testing (ages 25-34 years), the routine screening frequency (every 3-10 years), and management of HPV-positive, cytology-negative women. Model outcomes included reductions in lifetime cervical cancer risk, relative colposcopy rates, and colposcopy rates per cervical cancer prevented. Results: The age of switching to primary HPV testing and the screening frequency had the largest impacts on cancer risk reductions, which ranged from 90.9% to 96.3% compared to no screening. In contrast, increasing the follow-up intensity of HPV-positive, cytology-negative women provided only minor improvements in cancer benefits, but generally required considerably higher rates of colposcopy referrals compared to current levels, resulting in less efficient cervical cancer prevention. Conclusions: We found that in order to maximise cancer benefits HPV-based screening among unvaccinated women should not be delayed: rather, policy makers should utilise the triage mechanism to control colposcopy referrals.