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 eight years post-vaccination among men and women in the Netherlands, where bivalent HPV (2vHPV) vaccination, targeting HPV16/18, 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 (pre-vaccination) and repeated biennially among 16-24 year-old visitors of sexual health centers. We studied genital HPV positivity from 2009-2017 among women, heterosexual men, and unvaccinated women using Poisson GEE models, adjusted for individual- and population-level confounders. Trends were studied for 25 HPV types detected by the SPF10-LiPA25 platform. Results 6,354 women (64.7% self-reported unvaccinated) and 2,414 heterosexual men were included. Percentual declines in vaccine types HPV16/18 were observed for all women (12.6% per year (py); 95% confidence interval (CI) 10.6-14.5%), heterosexual men (13.0% py; 95% CI 8.3-17.5%), and unvaccinated women (5.4% py; 95% CI 2.9-7.8%). We observed significant declines in HPV31 (all women and heterosexual men), HPV45 (all women), and in all high-risk HPV types pooled (all women and heterosexual men). Significant increases were observed for HPV56 (all women) and HPV52 (unvaccinated women). Conclusion Our results provide evidence for first-order herd effects among heterosexual men against HPV16/18 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 2vHPV vaccination in a country with moderate vaccine uptake.

On the Elimination of Cancers Related to Oncogenic Human Papillomavirus: an Approach using a Computational Network Model

“…This result is in line with the conclusions of Lehtinen et al [23]. A recent study carried out in the Netherlands, a country with relatively moderate girls-only bivalent vaccine uptake, has also shown a herd effect between heterosexual men and unvaccinated women since the vaccination program began [24].…”

Evolution of human papilloma virus prevalence in a highly vaccinated region in Belgium: a retrospective cohort study in Flemish women (2010–2019)

“…In our age group 20–23 years old, there was an increase of HPV types 53, 58 and 67 over time. This so-called type-replacement is already found in other population-based trials with an increase of HPV types 39 and 51 in the Scandinavian and an increase of HPV types 54 and 56 in the Dutch populations (Gray et al , 2018; Hoes et al , 2021). Earlier, in 2016, an increase of types 39, 52, 53, 58 and 73 was observed in a meta-analysis (Mesher et al , 2016).…”

Ability of epidemiological studies to monitor HPV post-vaccination dynamics: a simulation study

“…Even the most recent studies, despite longer times since vaccine introduction (up to 8-10 years), had sample sizes too small to detect significant NV-prevalence variation, if it exists. [21,32,33] It seems important to note here that several studies reported a rapid reduction in the prevalences of HPV-31, -33 and -45 after vaccine introduction. [21,22,24,29] Nevertheless, this rapid reduction which differs from that observed in our simulations is most likely a direct protective effect of the vaccine via cross-reactivity, i.e., vaccine-induced antibodies able to neutralize these NV genotypes [18,27,28,34] but phylogenetically related to V genotypes.…”

“…Compared to our model simulations, most studies had smaller sample sizes than the required number of subjects we estimated and they were conducted only a few years after vaccine introduction. Even the most recent studies, despite longer times since vaccine introduction (up to 8–10 years), had sample sizes too small to detect significant NV-prevalence variation, if it exists [ 21 , 32 , 33 ]. It seems important to note here that several studies reported a rapid reduction in the prevalences of HPV-31, -33 and -45 after vaccine introduction [ 21 , 22 , 24 , 29 ].…”