Summary of Key Findings

Vaccine efficacy and safety. Data were considered from 11 clinical trials of 9vHPV, 4vHPV, and/or 2vHPV in adults aged 27 through 45 years, along with supplemental bridging immunogenicity data. In per-protocol analyses from three trials, 4vHPV and 2vHPV demonstrated significant efficacy against a combined endpoint of persistent vaccine-type HPV infections, anogenital warts, and cervical intraepithelial neoplasia (CIN) grade 1 (low-grade lesions) or worse. In nine trials, seroconversion rates to vaccine-type HPV after 3 doses of any HPV vaccine were 93.6%–100% at 7 months after the first dose. Overall evidence on benefits was GRADE evidence level 2, for moderate-quality evidence. In nine trials, few serious adverse events and no vaccine-related deaths were reported. Overall evidence on harms was also GRADE evidence level 2, for moderate-quality evidence. In the efficacy trial that was the basis for 9vHPV licensure for adults through age 45 years, per-protocol efficacy of 4vHPV among women aged 24 through 45 years was 88.7% (95% confidence interval [CI] = 78.1–94.8), and intention-to-treat efficacy was 47.2% (95% CI = 33.5–58.2) against a combined endpoint of persistent infections, extragenital lesions, and CIN 1+ related to HPV types 6, 11, 16, or 18 (9).

HPV burden of disease and impact of the vaccination program in the United States. Approximately 33,700 cancers are caused by HPV in the United States each year, including 12,900 oropharyngeal cancers among men and women, 10,800 cervical cancers among women, and 6,000 anal cancers among men and women; vaginal, vulvar, and penile cancers are less common (10). HPV vaccination for adolescents has been routinely recommended for females since 2006 and for males since 2011 (1). The existing HPV vaccination program for adolescents has the potential to prevent the majority of these cancers. Mean age at acquisition of causal HPV infection for cancers is unknown, but is estimated to be decades before cancer is diagnosed. In 2017, coverage with ≥1 dose of HPV vaccine was 65.5% among adolescents aged 13 through 17 years (11). Although coverage with the recommended number of doses remains below the Healthy People 2020 target of 80% for adolescents (12), the U.S. HPV vaccination program has resulted in significant declines in prevalences of vaccine-type HPV infections, anogenital warts, and cervical precancers (13). For example, prevalences of 4vHPV vaccine-type infection during 2013–2016, compared with those of the prevaccine era, declined from 11.5% to 1.8% among females aged 14 through 19 years and from 18.5% to 5.3% among females aged 20 through 24 years (14). In addition, declines have been observed among unvaccinated persons, suggesting protective herd effects (15).

Health economic analyses. Five health economic models of HPV vaccination in the United States were reviewed (16). The cost effectiveness ratio for the current HPV vaccination program ranged from cost-saving to approximately $35,000 per quality-adjusted life year (QALY) gained (16). In the context of the existing vaccination program, the incremental cost per QALY for expanding male vaccination through age 26 years was $178,000 in a subset of analyses in one of the five models reviewed using more favorable model assumptions for adult vaccination (16). In the context of the existing program, expanding vaccination to adults through age 45 years would produce relatively small additional health benefits and less favorable cost-effectiveness ratios. The incremental cost per QALY for also vaccinating adults through age 30 or 45 years exceeded $300,000 in four of five models (16). Variation in results across models was likely due to uncertainties about HPV natural history, such as prevalence of immunity after clearance of natural infections, and level of herd protection from the existing program. Under the existing program, in a subset of analyses in one of the five models reviewed using more favorable model assumptions for adult vaccination, the number needed to vaccinate (NNV) to prevent one case of anogenital warts, CIN grade 2 or worse (high-grade lesions), or cancer would be 9, 22, and 202, respectively. For expanding recommendations for males through age 26 years to harmonize catch-up vaccination across genders, these NNV would be 40, 450, and 3,260, respectively. For expanding recommendations to include adults through age 45 years, these NNV would be 120, 800, and 6,500, respectively (16).