Evidence to Recommendations for HPV Vaccination of Adults, Ages 27 through 45 years

The existing HPV vaccination program for U.S. adolescents has the potential to prevent the majority of these cancers. Mean age of acquisition of causal HPV infection for cancers is unknown, but estimated to be decades before cancer is diagnosed.

It is uncertain how much HPV-related morbidity and mortality is related to HPV infections acquired at ages 27 through 45 years. HPV incidence is highest among people in the age range of teens to early twenties. First HPV infections are acquired soon after first sexual activity. Most sexually active adults have been exposed to HPV, but a new sex partner is a risk factor for new HPV infections. The percentage of people reporting a new sex partner within the past year is lower in older age groups than among younger age groups.

Compared with the benefit of the existing HPV vaccination program for adolescents and young adults through age 26 years, the additional benefit of vaccinating people age 27 through 45 years would be minimal.

Based on modeling data, the number needed to vaccinate (NNV) to prevent one case of anogenital warts, cervical intraepithelial neoplasia (CIN) grade 2+, or cancer, is 9, 22, and 202, respectively, under the existing program. In a subset of analyses in the HPV-ADVISE model with more favorable model assumptions for adult vaccination, these NNV would be 120; 800; and 6,500 for expanding vaccination to include adults through age 45 years.

Clinical trials have shown that HPV vaccines are effective against infection and related disease due to HPV types that recipients are not infected with at the time of vaccination. In per-protocol analyses of efficacy results from 4vHPV and 2vHPV trials among adults older than age 26 years who were HPV-naïve, across 10 trials, HPV vaccines showed significant efficacy against a combined endpoint of persistent vaccine-type HPV infections, anogenital warts, and/or cervical intraepithelial neoplasia grade 1 or worse. Seroconversion rates to vaccine-type HPV following 3 doses of any HPV vaccine were 93.6–100% at 7 months post first dose.

In the FUTURE III trial in 3,819 women age 24 through 45 years, per-protocol efficacy of 4vHPV was 88.7% (95% CI 78.1, 94.8) against a combined endpoint of persistent HPV infection, extragenital lesions, and/or CIN 1+. When analysis was restricted to women age 27 through 45 years, efficacy was 87.7% (95% CI, 75.4, 94.6). No significant efficacy was observed against CIN 2+, although the study was not powered to evaluate for this endpoint specifically. Ten-year follow-up of a subset of women in this study found no waning protection.

In a 9vHPV immunogenicity trial, geometric mean antibody titers to 7 high-risk HPV types were non-inferior in 642 women age 27–45 years compared to 570 women age 16–26 years; >99% of women in both groups seroconverted to all 9vHPV types.

In clinical trials, intention-to-treat (ITT) results had lower observed efficacy than per-protocol analyses, since ITT analyses included participants with previous exposures and prevalent vaccine-type HPV infections at baseline before initial vaccination.

In the FUTURE III trial in 3,819 women age 24–45 years, ITT efficacy of 4vHPV was 47.2% (95% CI 33.5, 58.2) against a combined endpoint of persistent HPV infection, extragenital lesions, and/or CIN 1+. No significant efficacy was observed against CIN 2+, although the study was not powered to evaluate for this endpoint specifically.

Certainty of the evidence on safety is Level 2 (Moderate)

Overall evidence on benefits in the per-protocol population was GRADE evidence level 2 (moderate quality evidence). Overall evidence on harms was also GRADE evidence level 2 (moderate quality evidence).

Acceptability was higher when the vaccine was assumed to be free and/or a health care provider made a recommendation.

Variation in results across models was likely due to uncertainties about HPV natural history (e.g., burden of HPV-associated disease caused by new HPV infections after age 26 years, and prevalence of immunity following clearance of natural infections) and level of herd protection from the existing HPV vaccination program.

It is not clear whether any recommendation for HPV vaccination in this age range would lead to greater uptake among individuals who are likely versus unlikely to benefit.

Programs and funding for adult vaccination are not available in all jurisdictions. Adult immunization is performed primarily in the private sector.

In a 2015 survey of 353 obstetrician/gynecologists, 81% reported that they stock and administer HPV vaccine.

Identifying individual patients likely to benefit from adult HPV vaccination could be challenging for vaccine providers, especially those who do not regularly assess sexual risk behaviors.

Some Work Group members felt that recommending vaccination in this age range might reduce health disparities, by increasing access to vaccination among adults with health insurance coverage. Others felt that recommending vaccination in this age range might enhance health disparities, as underinsured adults would be less likely to have access to vaccination since states have limited funds for adult vaccination programs.