Potential impact of switching from a two- to one-dose gender-neutral routine HPV vaccination program in Canada: A mathematical modeling analysis

Background Worldwide, countries are examining whether to implement one-dose HPV vaccination. To inform policy recommendations in Canada, we used mathematical modeling to project the population-level impact and efficiency of switching from two-to one-dose gender-neutral routine HPV vaccination. Methods We used HPV-ADVISE, an individual-based transmission-dynamic model of HPV infections/diseases, to model 2 provinces (Quebec, Ontario), which represent higher (≈85%) and lower (≈65%) HPV vaccination coverage in Canada. We examined non-inferior and pessimistic scenarios of one-dose efficacy (VE=98%, 90%) and average duration (VD=lifelong, 30 years, 25 years) versus two doses (VE=98%, VD=lifelong). Our main outcomes were the relative reduction in HPV-16 (among females/males) and cervical cancers, and the number of doses needed to prevent one cervical cancer (NNV). Results Our model projects that one-dose HPV vaccination would avert a similar number of cervical cancers as two doses in Canada, under various non-inferior and pessimistic scenarios. Under the most pessimistic scenario (VD=25 years), one-dose vaccination would avert ∼3 percentage-points fewer cervical cancers than two doses over 100 years. All one-dose scenarios were projected to lead to cervical cancer elimination and were projected to be a substantially more efficient use of vaccine doses compared to two doses (NNVs one-dose vs no vaccination=800-1000; incremental NNVs two-dose vs one-dose vaccination >10,000). Interpretation If the average duration of one-dose protection is longer than 25 years, individuals would be protected during their peak ages of sexual activity and one-dose vaccination would prevent a similar number of HPV-related cancers, while being a more efficient use of vaccine doses. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Public Health Agency of Canada (PHAC), Canadian Institutes of Health Research (CIHR), Bill and Melinda Gates Foundation (PATH/Single dose HPV vaccine evaluation consortium), Canadian Immunization Research Network (CIRN) ### 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 Model outputs are available upon reasonable request.