Cervical cancer screening in low-resource settings: A cost-effectiveness framework for valuing tradeoffs between test performance and program coverage

As cervical cancer screening programs are implemented in low-resource settings, protocols are needed to maximize health benefits under operational constraints. Our objective was to develop a framework for examining health and economic tradeoffs between screening test sensitivity, population coverage and follow-up of screen-positive women, to help decision makers identify where program investments yield the greatest value. As an illustrative example, we used an individual-based Monte Carlo simulation model of the natural history of human papillomavirus (HPV) and cervical cancer calibrated to epidemiologic data from Uganda. We assumed once in a lifetime screening at age 35 with two-visit HPV DNA testing or one-visit visual inspection with acetic acid (VIA). We assessed the health and economic tradeoffs that arise between (i) test sensitivity and screening coverage; (ii) test sensitivity and loss to follow-up (LTFU) of screen-positive women; and (iii) test sensitivity, screening coverage and LTFU simultaneously. The decline in health benefits associated with sacrificing HPV DNA test sensitivity by 20% (e.g., shifting from provider- to self-collection of specimens) could be offset by gains in coverage if coverage increased by at least 20%. When LTFU was 10%, two-visit HPV DNA testing with 80-90% sensitivity was more effective and more cost-effective than one-visit VIA with 40% sensitivity and yielded greater health benefits than VIA even as VIA sensitivity increased to 60% and HPV test sensitivity declined to 70%. As LTFU increased, two-visit HPV DNA testing became more costly and less effective than one-visit VIA. Setting-specific data on achievable test sensitivity, coverage, follow-up rates and programmatic costs are needed to guide decision making for cervical cancer screening. What's new? Cervical cancer is a leading cause of cancer death among women worldwide, despite the fact that the disease is preventable through screening programs. While routine screening with Pap smear testing has reduced incidence in high-income countries, implementation has largely been unsuccessful in low-resource settings due to insufficient budgets, lack of healthcare delivery infrastructure and competing health priorities. Tailored protocols that maximize health benefits under operational constraints are needed. This study presents a framework for examining health and economic tradeoffs between screening test sensitivity, population coverage and follow-up of screen-positive women, to help decision-makers identify where program investments yield the greatest value.