Methods: We developed a first-order Monte Carlo simulation model of the natural history of HPV and cervical cancer in which transitions between health states were dependent on HPV type, age, and history. To calibrate the model to a population in Brazil, we performed a random search over feasible ranges of input parameters (e.g., incidence of type-specific HPV infection, type-specific immunity following a single HPV infection) and generated over 500,000 unique natural history parameter sets. Each set was scored according to its fit to multiple calibration target data using likelihood functions based on primary data from Brazil and the published literature. Using 50 of the best fitting parameters sets, we estimated lifetime costs, years of life saved (YLS), and incremental cost-effectiveness ratios (ICERs) associated with screening alone, vaccination alone, or a combined approach. Screening strategies differed by initial test (HPV testing, cytology), number of visits, targeted age, and frequency. We assumed the vaccine was given at age 12, efficacy was 100% against types 16 and 18, 70% of the eligible population was covered, and immunity was lifelong.

Results: The mean reduction in lifetime cancer risk for vaccination alone was 48%, and for vaccination plus screening three times per lifetime (between ages 35-45 at 5-year intervals) was 66%, assuming 70% coverage. At a cost of $25 per vaccinated woman, vaccination alone was cost-saving relative to no intervention. Using the 50 best fitting parameter sets, vaccination plus screening three times per lifetime ranged from $130 to $163 per YLS. Provided the cost per vaccinated woman was less than $50, all strategies that employed screening alone were dominated by vaccination. As the cost per vaccinated woman approached $100, the strategy of vaccination alone became dominated, and screening options were no longer dominated, with ICERs below $1,000 per YLS. When the cost per vaccinated woman was increased to $360 (the vaccine price estimated for the U.S.), vaccination plus screening three times per lifetime increased to more than $10,000 per YLS.

Conclusions: Using the per capita GDP in Brazil (I$7423) as a cost-effectiveness threshold, we would consider vaccination plus screening three times per lifetime to be a very cost-effective strategy.