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

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

No evidence for cross-protection of the HPV-16/18 vaccine against HPV-6/11 positivity in female STI clinic visitors

Objectives Data from a vaccine trial and from post-vaccine surveillance in the United Kingdom have suggested that the bivalent HPV-16/18 vaccine offers cross-protection against HPV-6/11 and protection against anogenital warts (AGW). We studied the effect of the bivalent vaccine on genital HPV-6/11 positivity and AGW in the Netherlands. Methods We included all vaccine-eligible women from the PASSYON study, a biennial cross-sectional study among 16- to 24-year-old sexually transmitted infection (STI) clinic attendants. Vaginal self-swabs were analyzed for type specific HPV and AGW were diagnosed at the STI-clinic. Prevalence of HPV-6 and/or HPV-11 and AGW were compared between self-reported vaccinated and unvaccinated women by log-binomial regression analysis, adjusted for demographics and risk behavior. Results Of the 1198 women included, 56% reported to be vaccinated at least once. Relative to unvaccinated women, the adjusted prevalence ratio (PR) for HPV-6/11 was 1.03 (95% confidence interval [CI] 0.74–1.43) for women vaccinated at least once. The crude PR for AGW was 0.67 (95% CI 0.22–2.07) for women vaccinated at least once. Adjustment did not change these results. Conclusions We observed no cross-protective effect of the bivalent vaccine on genital HPV-6/11 positivity and a non-significant partially protective effect on AGW

Assessment of herd effects among women and heterosexual men after girls-only HPV16/18 vaccination in the Netherlands:A repeated cross-sectional study

Data on the impact of human papillomavirus (HPV) vaccination on the population HPV prevalence are largely obtained from women. We assessed the impact of the girls-only HPV16/18 vaccination program in the Netherlands that started in 2009, on trends in HPV prevalence among women and heterosexual men, using data from the PASSYON study. In this cross-sectional study, the HPV prevalence among 16- to 24-year-old visitors to sexually transmitted infection clinics was assessed in 2009, 2011, 2013, and 2015. We compared the genital postvaccination HPV prevalence with the prevaccination prevalence (2009) using Poisson GEE models. In total, we included 4,996 women and 1,901 heterosexual men. The percentage of women who reported to be vaccinated increased from 2.3% in 2009 to 37% in 2015. Among all women, the HPV16/18 prevalence decreased from 23% prevaccination to 15% in 2015 (adjusted prevalence ratio [aPR] 0.62, p(trend) <0.01). Among heterosexual men, the HPV16/18 prevalence decreased from 17% prevaccination to 11% in 2015 (aPR 0.52, p(trend) <0.01). Of the heterosexual men with a steady partner, HPV16/18 prevalence was lower among those whose steady partner had been vaccine-eligible in the national immunization program (aPR 0.13). Among unvaccinated women, the HPV16/18 prevalence in 2015 was not different from prevaccination. The decreasing HPV16/18 prevalence among heterosexual men and the reduced HPV16/18 prevalence among heterosexual men with a vaccine-eligible steady partner strongly suggests herd protection from girls-only vaccination. Absence of notable herd effects among unvaccinated women 6 years postvaccination may be due to the moderate vaccine uptake among girls in the Netherlands. What's new? Human papillomavirus (HPV) is a sexually transmitted virus that plays a causal role in the development of anogenital and oropharyngeal cancers in both men and women. The population-level impact of HPV vaccination programs on the HPV prevalence has however mainly been studied in women. This study shows decreasing trends in the HPV16 and HPV18 prevalence among both women and heterosexual men after the introduction of a girls-only HPV16/18 vaccination program in the Netherlands. The findings provide compelling evidence for herd protection in men. Because HPV16/18 are the most oncogenic types, HPV-related cancers are expected to decline in both sexes after girls-only HPV vaccination