Understanding the key determinants of an HPV therapeutic vaccine: a modeling analysis

Despite incredibly effective tools to prevent HPV infection and treat precancerous lesions, the scale-up of existing interventions in most low and middle-income countries has been slow, leaving a residual burden of invasive cervical cancer that will persist for decades. An HPV therapeutic vaccine may overcome some of the scalability and infrastructure challenges of traditional screening and treatment programs, though its potential public health value depends upon its characteristics, delivery strategy, and the underlying immunity of the population on which it would act. This analysis uses HPVsim, an open-access agent-based simulation framework, to evaluate the impact of a range of potential HPV therapeutic vaccines with varying scale-up of existing preventive interventions in nine high-burden low- and middle-income countries (LMICs). For each setting, the model is populated with context-specific demographic and behavioral data, and calibrated to fit estimates of HPV and cervical disease by age. We find that an HPV therapeutic vaccine that clears 90% of virus and regresses 50% of high-grade lesions, reaching 70 percent of 35-45 year old women starting in 2030, could avert 1.2-2.2 million incident cases of cervical cancer, 500,000-1.2 million cervical cancer deaths and 20-40 million disability adjusted life years (DALYs) in the modeled high-burden LMICs over 30 years. The size of the impact is sensitive to rates of background intervention scale-up and the characteristics of the vaccine, including ability to establish long-lasting immune memory. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding. ### 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I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the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 All data produced are available online at https://github.com/amath-idm/hpvsim\_txvx\_analyses [https://github.com/amath-idm/hpvsim\_txvx\_analyses][1] [1]: https://github.com/amath-idm/hpvsim_txvx_analyses