Projected health and economic effects of nonavalent versus bivalent human papillomavirus vaccination in the Netherlands: a data-driven analysis

Background The national immunization program in the Netherlands currently uses the bivalent human papillomavirus (HPV) vaccine, targeting HPV genotypes 16 and 18. It is not yet clear whether it is cost-effective to switch to the nonavalent vaccine, targeting an additional seven HPV genotypes. This study compares the health and economic effects of both vaccines for the Dutch setting of sex-neutral vaccination with tender-based procurement and HPV-based screening for cervical cancer. Methods We estimated the population effects under bivalent or nonavalent HPV vaccination in a cohort of girls and boys, invited for vaccination at 10 years of age. The differential impact of nonavalent versus bivalent HPV vaccination was obtained by projecting type-specific risk reductions, obtained by an HPV transmission model, onto type-specific outcomes of HPV-based screening, incidence of HPV-related cancers in both men and women, as well as treatment for anogenital warts and recurrent respiratory papillomatosis. Bayesian analysis was applied to translate the uncertainty of the data into credible intervals (CI) for health and economic outcomes, under specific scenarios regarding long-term vaccine uptake, efficacy and cost. The base-case scenario assumed 50% uptake at age 10, life-long vaccine protection with cross-protective efficacy to HPV 31, 33 and 45 from the bivalent vaccine, and an additional cost of EUR 35 per 2-dose vaccination schedule for the nonavalent vaccine. Results In the base-case scenario, nonavalent vaccination is expected to prevent 1090 additional cases of high-grade cervical intraepithelial neoplasia (CIN2/3), 70 additional cases of HPV-related cancer, 34 000 episodes of anogenital warts and 28 onsets of RRP, relative to bivalent vaccination per cohort of 100 000 girls and 100 000 boys. These health effects translate into an incremental cost-effectiveness ratio (ICER) of EUR 2048 (95% CI: 716 to 3141) per life-year gained, under annual discounting of 1.5% and 4% for future health and economic effects, respectively. The ICER remained below the local threshold for cost-effective preventive interventions in all investigated scenarios, except when assuming waning efficacy for non-16/18 oncogenic HPV types with either vaccine or cross-protection to non-31/33/45 types for the bivalent vaccine. Conclusions Sex-neutral vaccination with the nonavalent vaccine is likely to be cost-effective relative to the currently used bivalent vaccine in the Netherlands. Monitoring long-term type-specific vaccine effectiveness is key to update projections on the impact and cost-effectiveness of HPV vaccination. ### Competing Interest Statement JAB is co-PI on the investigator-initiated research project HPV4M (Human papillomavirus vaccine effectiveness study among men who have sex with men), conducted at the Public Health Service of Amsterdam and financed by GSK. BS and JB report no financial relationships or conflicts of interest regarding the content herein. ### Funding Statement This paper is part of the project "HPV-COMPARE: Comparing the health and economic effects of different HPV vaccines and catch-up strategies of young adults in the Netherlands" funded by the Netherlands Organization for Health Research and Development (ZonMw, grant 10150511910059). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data and code are available through GitHub, via BirgitSollie/HPV-COMPARE