To examine tradeoffs between cervical cancer screening test performance (sensitivity, specificity) and programmatic considerations (population coverage, follow-up of screen-positive women) in low-resource settings.
Method:
Using 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 screening occurred once in a woman's lifetime at age 35 with two-visit HPV DNA testing or one-visit visual inspection with acetic acid (VIA). Model outcomes included reduction in lifetime risk of cancer and incremental cost-effectiveness ratios (ICERs). For each screening modality, we performed one- and two-way sensitivity analyses to assess the tradeoffs between 1) test sensitivity and specificity; 2) test sensitivity and screening coverage; and 3) screening coverage and follow-up rates of screen-positive women. Sensitivity, specificity and coverage were varied 30-100% and loss-to-follow-up rates were varied from 15-60% per clinical contact. To assess the tradeoff between test sensitivity and loss-to-follow-up given uncertainty, we compared HPV DNA testing with 80-100% sensitivity to VIA with 40-60% sensitivity, as loss-to-follow-up varied from 15-60%.
Result:
For both screening modalities, improving test sensitivity had greater potential to reduce the ICER of onetime screening relative to comparable improvements in test specificity, due to the potential for increased benefits relative to costs incurred. While there were similar reductions in cancer risk for comparable changes in coverage and sensitivity, the costs associated with increasing coverage were proportional to benefits, yielding stable ICERs; as sensitivity increased from 30-100%, ICERs decreased by 65% (HPV testing). A comparison of HPV DNA testing and VIA found that when loss-to-follow-up per clinical contact was low (i.e., 15%), HPV testing yielded greater cancer risk reductions than VIA at all assumed levels of sensitivity. When loss-to-follow-up rates reached 60% per visit, a perfectly sensitive HPV test yielded similar cancer risk reductions as the least sensitive VIA program considered. The rank ordering of strategies changed dramatically as sensitivity and loss-to-follow-up varied.
Conclusion:
Available screening modalities pose tradeoffs between test performance, coverage, and follow-up. Where screening is limited, test sensitivity and follow-up of screen-positive women are critical determinants of the relative effectiveness and cost-effectiveness of prevention programs.