Purpose: Vaccination against HPV 16 and 18, two types responsible for the majority of invasive cervical cancer, is highly efficacious in girls not previously infected with these types. While there is consensus that young girls are the ideal vaccine target, the Centers for Disease Control and Prevention recommends catch-up vaccination through 26-years. We assess the cost-effectiveness of these recommendations in the context of current screening.

Methods: We contextualized our dynamic transmission model of HPV-16,18 to the U.S. incorporating sexual contact patterns based on data from population-based surveys. Uncertain parameters, such as transmission between partners, were calibrated to empirical data from epidemiological studies. The empirically-calibrated model was used to generate HPV-16,18 incidence by age, gender, and calendar time under different vaccination scenarios. These estimates served to parameterize our first-order simulation model, which includes vaccine-targeted and non-targeted HPV types, and we estimated the reduction in lifetime cancer risk and cost-effectiveness of vaccinating adolescent girls (~age 10-12), as well as women up to age 21 or 26, at 75% coverage. We included scenarios of vaccination and screening, assuming annual cytology starting at age 18, as well as less frequent screening at later ages. We assumed a cost per-vaccinated woman of $500 (three-doses, supplies/administration, counseling).

Results: Adolescent vaccination, when added to annual cytology in 90% of women, increased cancer reduction from 77% to 92%. As the upper bound for a catch-up vaccination was increased to age 21 or 26, the marginal benefit of vaccination decreased while marginal cost increased. Combined vaccination and current screening cost over $150,000 per year of life (YLS) saved, whereas vaccination and delayed screening at less frequent intervals (e.g., every 5 years from age 25) was less than $50,000 per YLS. Vaccination strategies that specifically target women older than 21 were dominated by those that target girls younger than 12. We found that relatively modest herd immunity effects (identified using the dynamic model) were offset by relatively modest increases in cancer attributable to non-16,18 HPV types (identified using the simulation model).

Conclusions: The cost-effectiveness of HPV vaccination in the U.S. will likely be optimized by focusing on achieving high coverage in young adolescents, screening vaccinated women less frequently, and targeting initial catch-up efforts to those women between 13 and 21.