Lauri E. Markowitz

Background: Efficacy and immunogenicity of single-dose human papillomavirus (HPV) vaccination have been demonstrated among females; less is known about single-dose vaccination among males. We assessed sex differences in antibody response 12–48 months postvaccination among adolescents who received a single 9-valent HPV vaccine (9vHPV) dose. Methods: Participants were recruited from an integrated healthcare delivery system in Oregon and southwest Washington. Adolescents who received a single 9vHPV dose at ages 9–12 years, 12–48 months prior to study enrollment, were identified. Serum antibody testing for each 9vHPV type (HPV types 6, 11, 16, 18, 31, 33, 45, 52, 58) was conducted using M9ELISA. We compared antibody detection and geometric mean antibody concentrations (GMCs) among males to females. Results: Among 111 male and 96 female participants, age at vaccination (>95% at age 11 or 12 years) and time since vaccination (median, 20 months) were similar by sex. Among males and females, 80.2% and 89.6%, respectively, had detectable antibodies for all types, with no significant sex difference. Type-specific detection ranged from 84.7% to 99.1% for males and 91.7% to 99.0% for females, with no significant sex differences. GMCs were 31%–50% lower among males than females for all types (range of GMC ratios adjusted for time since vaccination, 0.50–0.69). Conclusions: One to 4 years after single-dose 9vHPV vaccination, males had similar detection but lower antibody concentrations than females. Because very low levels of antibody are thought to protect against HPV, the clinical significance of these sex differences is unknown.

Supplementary Table 1 shows characteristics by HPV typing data availability, HPV 16/18 results, and vaccination status.

Supplementary Figure 1 shows the different assays used for HPV typing by collection date, HPV-IMPACT, 2008 to 2019.

Supplementary Table 2 supports figure 2 in the main text and includes the proportions of CIN2+ that were HPV16/18 positive that are used to make the graphs.

Background:Monitoring human papillomavirus (HPV) types detected in cervical precancers has been one approach to evaluate HPV vaccination impact in the United States. During 2008 to 2014, the proportion of cervical precancers positive for HPV16/18 decreased overall and among some demographic and histologic subgroups. This updated analysis describes trends through 2019.Methods:We analyzed cervical precancers among women 20 to 39 years of age from a five-site, population-based surveillance program for cervical intraepithelial neoplasia grade 2 or higher and adenocarcinoma in situ (AIS; collectively CIN2+). Available archived diagnostic tissue was tested for HPV16, HPV18, and other HPV types. We evaluated the average annual percent change (AAPC) in the proportion of cervical precancers with HPV16 or 18 detected overall and by vaccination status, age group, diagnosis, race/ethnicity, and surveillance site.Results:During 2008 to 2019, 17,323 CIN2+ cases had valid typing results. The proportion of cases positive for HPV16/18 significantly decreased by 3.6% per year. The largest decrease occurred among cases in vaccinated women (AAPC = −8.9), with smaller but still significant decreases among unvaccinated women (AAPC = −2.3). Significant decreases were observed among all subgroups evaluated, except women 35 to 39 years of age, AIS, and Asian women.Conclusions:During 2008 to 2019, decreases in the proportion of CIN2+ cases that were HPV16/18 positive among vaccinated and unvaccinated women and in most subgroups evaluated suggest direct and indirect HPV vaccination impact.Impact:HPV vaccination impact on precancers is prognostic of future decreases in cervical cancer. Continued monitoring can enable evaluation of vaccination impact in population subgroups.

Background: Monitoring human papillomavirus (HPV) types detected in cervical precancers has been one approach to evaluate HPV vaccination impact in the United States. During 2008 to 2014, the proportion of cervical precancers positive for HPV16/18 decreased overall and among some demographic and histologic subgroups. This updated analysis describes trends through 2019. Methods: We analyzed cervical precancers among women 20 to 39 years of age from a five-site, population-based surveillance program for cervical intraepithelial neoplasia grade 2 or higher and adenocarcinoma in situ (AIS; collectively CIN2+). Available archived diagnostic tissue was tested for HPV16, HPV18, and other HPV types. We evaluated the average annual percent change (AAPC) in the proportion of cervical precancers with HPV16 or 18 detected overall and by vaccination status, age group, diagnosis, race/ethnicity, and surveillance site. Results: During 2008 to 2019, 17,323 CIN2+ cases had valid typing results. The proportion of cases positive for HPV16/18 significantly decreased by 3.6% per year. The largest decrease occurred among cases in vaccinated women (AAPC = −8.9), with smaller but still significant decreases among unvaccinated women (AAPC = −2.3). Significant decreases were observed among all subgroups evaluated, except women 35 to 39 years of age, AIS, and Asian women. Conclusions: During 2008 to 2019, decreases in the proportion of CIN2+ cases that were HPV16/18 positive among vaccinated and unvaccinated women and in most subgroups evaluated suggest direct and indirect HPV vaccination impact. Impact: HPV vaccination impact on precancers is prognostic of future decreases in cervical cancer. Continued monitoring can enable evaluation of vaccination impact in population subgroups.

In June 2019, the U.S. Advisory Committee on Immunization Practices recommended shared clinical decision making regarding potential human papillomavirus (HPV) vaccination of men and women aged 27 to 45 years ("mid-adults"). To examine the incremental cost-effectiveness ratios (ICERs) and number needed to vaccinate (NNV) to prevent 1 HPV-related cancer case of expanding HPV vaccination to subgroups of mid-adults at increased risk for HPV-related diseases in the United States. Individual-based transmission dynamic modeling of HPV transmission and associated diseases using HPV-ADVISE (Agent-based Dynamic model for VaccInation and Screening Evaluation). Published data. All U.S. mid-adults and higher-risk subgroups within this population. 100 years. Health care sector. Expanding 9-valent HPV vaccination to mid-adults and higher-risk subgroups. ICERs and NNVs. Expanding 9-valent HPV vaccination to all mid-adults, those with more lifetime partners, and those who have just separated was projected to cost an additional $2 005 000, $763 000, and $1 164 000 per quality-adjusted life-year (QALY) gained, respectively. The NNVs to prevent 1 additional HPV-related cancer case were 7670, 3190, and 5150, respectively, compared with 223 for vaccination of persons aged 9 to 26 years (vs. no vaccination). The mid-adult strategy with the lowest ICER and NNV was vaccinating infrequently screened mid-adult women who have just separated and have a higher number of lifetime sex partners (ICER, $86 000 per QALY gained; NNV, 470). Uncertainty about rate of new sex partners and natural history of HPV among mid-adults. Vaccination of mid-adults against HPV is substantially less cost-effective and produces higher NNVs than vaccination of persons younger than 26 years under all scenarios investigated. However, cost-effectiveness and NNV are projected to improve when higher-risk mid-adult subgroups are vaccinated, such as mid-adults with more sex partners and who have recently separated, and women who are underscreened. Centers for Disease Control and Prevention.

A 24-year-old woman is being seen for routine health care. She has not received any vaccinations against human papillomavirus (HPV). The patient initiated sexual activity at 18 years of age and has had three male sex partners. What would you recommend regarding HPV vaccination?