Population Impact of Girls-Only Human Papillomavirus 16/18 Vaccination in The Netherlands: Cross-Protective and Second-Order Herd Effects

Abstract

Background: Human papillomavirus (HPV) vaccination programs achieve substantial population-level impact, with effects extending beyond protection of vaccinated individuals. We assessed trends in HPV prevalence up to 8 years postvaccination among men and women in the Netherlands, where bivalent HPV vaccination, targeting HPV types 16/18, has been offered to (pre)adolescent girls since 2009 with moderate vaccination coverage.

Methods: We used data from the PASSYON study, a survey initiated in 2009 (prevaccination) and repeated biennially among 16- to 24-year-old visitors of sexual health centers. We studied genital HPV positivity from 2009 to 2017 among women, heterosexual men, and unvaccinated women using Poisson generalized estimating equation models, adjusted for individual- and population-level confounders. Trends were studied for 25 HPV types detected by the SPF10-LiPA25 platform.

Results: A total of 6354 women (64.7% self-reported unvaccinated) and 2414 heterosexual men were included. Percentual declines in vaccine types HPV-16/18 were observed for all women (12.6% per year [95% confidence interval {CI}, 10.6-14.5]), heterosexual men (13.0% per year [95% CI, 8.3-17.5]), and unvaccinated women (5.4% per year [95% CI, 2.9-7.8]). We observed significant declines in HPV-31 (all women and heterosexual men), HPV-45 (all women), and in all high-risk HPV types pooled (all women and heterosexual men). Significant increases were observed for HPV-56 (all women) and HPV-52 (unvaccinated women).

Conclusions: Our results provide evidence for first-order herd effects among heterosexual men against HPV-16/18 and cross-protective types. Additionally, we show second-order herd effects against vaccine types among unvaccinated women. These results are promising regarding population-level and clinical impact of girls-only bivalent HPV vaccination in a country with moderate vaccine uptake.

Keywords: HPV; herd immunity; human papillomavirus; population effects; type replacement; vaccination.

Figure 1.

Prevalence of human papillomavirus (HPV) for the different years of the Papillomavirus Surveillance Among STI Clinic Youngsters in the Netherlands (PASSYON) study among all women (A), heterosexual men (B), and unvaccinated women (C). From 2015 onward, the access policy at the sexual health centers had changed, leading to prioritizing of individuals at high risk for sexually transmitted infections. *HPV-68 also includes HPV-73 and HPV-97.

Figure 2.

Percentual change in prevalence of high-risk and low-risk human papillomavirus (HPV) types per year, among all women (A), heterosexual men (B), and unvaccinated women (C). Percentual change in prevalence per year was calculated by exponentiating the adjusted regression coefficients of study year, which was added as a continuous variable in generalized estimating equation analyses. For the exact Percentual changes per year, see Supplementary Table 4. *HPV-68 also includes HPV-73 and HPV-97. #Point estimate for HPV-34 among heterosexual men was –26%. The x-axes differ between all women, heterosexual men, and unvaccinated women. Regression coefficients for all women were adjusted for age, policy change at the sexual health center, lifetime sex partners, history of any sexually transmitted infection (STI), steady partner, notified for STI, sex partners past 6 months, and condom use with casual partner. Regression coefficients for heterosexual men were adjusted for age, policy change at the sexual health center, lifetime sex partners, and history of any sexually transmitted infection. Regression coefficients for the unvaccinated women were adjusted for age, policy change at the sexual health center, lifetime sex partners, history of any sexually transmitted infection, notified for STI, sex partners past 6 months, and condom use with casual partner.