Allison Portnoy

Introduction: Human papillomavirus (HPV) is a leading cause of both cervical and non-cervical cancers, including anal, oropharyngeal, vaginal and vulvar cancers. While most HPV vaccination impact assessments have focused on preventing cervical cancer among women, the broader benefits of vaccination against other HPV-attributable cancers in low- and middle-income countries (LMICs) remain less explored. Methods: We used a static cohort model to assess the potential health impact of bivalent HPV vaccination on HPV-attributable female non-cervical cancers in 117 LMICs from 2030 to 2100. The model incorporated country-specific data on cancer mortality, HPV type distribution, demographic projections and vaccine coverage. Sensitivity analyses were performed to account for uncertainties in cancer incidence, cancer mortality and HPV type distribution. Results: Our projections suggest that HPV vaccination could contribute to prevention of approximately five 90 000 cases of anal, 880 000 cases of oropharyngeal, 1.27 million cases of vaginal and 2.18 million cases of vulvar cancers over the analytic period. In total, 3.02 million deaths from these non-cervical cancers among women could be averted by 2100. The African region is expected to see the largest relative reductions in both cases and deaths while the European region showed the smallest gains. By the end of the century, 58 countries are projected to reach at least a 25% reduction in anal cancer mortality compared with just 25 countries for oropharyngeal cancer. These findings reflect substantial regional disparities in both burden and vaccination impact. Conclusion: HPV vaccination holds considerable promise in reducing the burden of non-cervical cancers among women in LMICs, especially in regions with high incidence and limited access to care. Recognising and harnessing these broader benefits can strengthen the public health case for scaling up vaccine access, implementing region-specific strategies and investing in equitable healthcare systems to decrease global disparities.

Background The tuberculosis (TB) vaccine candidate VPM1002 did not prove efficacy in the recent Phase III trial and is in discussion with the Indian regulator. However, low efficacy TB vaccines may still have public health value. We estimated the potential health and economic impact of introducing VPM1002 in low- and middle-income countries (LMICs). Methods We calibrated compartmental TB dynamic models to epidemiologic and demographic data for 79 individual LMICs. We assumed the vaccine would be introduced between 2027-2047, delivered routinely and annually to the age six cohort and delivered in two 10-yearly campaigns for older ages, be efficacious for 3 years, have efficacy of 16.9% (95% confidence interval = -13.3 to 39.1%), and prevent TB disease. We estimated the cumulative symptomatic TB episodes and TB-associated deaths averted by 2050, and cost-effectiveness from health-system and societal perspectives. Results Results suggest, across 79 LMICs, there may be 6.7 (95% uncertainty interval = -4.0 to 14.9) million symptomatic TB episodes averted, and 0.7 (-0.4 to 1.5) million TB-associated deaths averted overall over 2027-2050. At an assumed vaccine cost of 0.75 USD per dose, VPM1002 vaccination may be cost-effective compared to no vaccination in 15 of 79 modelled LMICs (19%), assuming a threshold of 1-times per-capita gross domestic product from the health system perspective, and may be cost-effective in 28 out of 79 countries (35%) and dominant in 14 countries (18%) from the societal perspective. Conclusions The VPM1002 Phase III trial did not prove efficacy, therefore results could be due to chance. However, if the true vaccine efficacy was consistent with the observed point estimate, then overall rollout in LMICs may avert a portion of symptomatic TB cases and TB-associated deaths, and in some countries could be cost-effective/saving. Although potentially infeasible, it would be useful to obtain more precise estimates of VPM1002 efficacy through larger Phase III/IV studies.

The Immunization Agenda 2030 calls for reaching all people with immunization services, including ‘zero-dose’ children—children who have not received any routine vaccines. To plan and finance efforts to fully vaccinate these children and improve coverage and equity, decision-makers need reliable cost estimates. However, primary data on the costs of reaching zero-dose children, typically part of disadvantaged and hard-to-reach populations, are scarce. This study approximates these costs using standardized, country-level estimates of vaccine delivery unit costs for outreach delivery in low- and middle-income countries (LMICs). We extracted outreach delivery cost-per-dose estimates for childhood immunization services from the 2024 update of the Immunization Delivery Cost Catalogue. Using these data, we developed a meta-regression model to estimate standardized outreach vaccine delivery unit costs. The generalized linear model assumed a Gamma-distributed outcome with a log link and included both country-level and study-level predictors: study year, economic or financial cost basis, routine or campaign delivery, and full or incremental costing approach. The fitted model was used to estimate 2024 outreach delivery costs per dose for 129 LMICs. The model was estimated using 48 observations from 19 countries focused on outreach or mobile vaccine delivery. The best-fitting specification included diphtheria-tetanus-pertussis (DTP1) coverage, per-capita gross domestic product, and under-five population size as predictors. For 2024, the predicted mean economic cost per dose was $8.65 (95% credible interval $2.33–23.71), averaged across all 129 LMICs. To fully immunize a zero-dose child with 13 recommended vaccinations, the equivalent cost estimate was $112.45 ($30.29–308.23). Reaching zero-dose children is crucial for improving equity in global health, and estimates of the costs of doing so are needed to inform budgeting for immunization programs. These meta-regression-based cost estimates can help countries to improve budgeting, planning, and resource allocation for efforts to reach zero-dose children.

Widespread vaccination for human papillomavirus (HPV) alters the landscape of cervical cancer (CC) risk, requiring adaptations to the CC screening program. To assess the cost-effectiveness and harm-benefit tradeoffs of adapting CC screening strategies on the basis of age at HPV vaccination. Individual-based mathematical modeling study. Published data. Hypothetical cohorts of women vaccinated in 7 different age groups (12, 13 to 15, 16 to 18, 19 to 21, 22 to 24, 25 to 27, and 28 to 30 years) with either bivalent or nonavalent vaccines in Norway. Lifetime. Extended health care sector (that is, including patient time and travel costs). HPV-based screening strategies that varied screening start age, interval, and number of lifetime screening tests. Incremental cost-effectiveness ratios, defined as the additional cost per quality-adjusted life-year (QALY) gained. "Preferred" (that is, cost-effective) screening for each age group was identified using a cost-effectiveness threshold of $55 000 per QALY. Harm-benefit tradeoffs were quantified as the ratio of colposcopy referrals to CC cases averted. For all vaccination age groups and both vaccines, less frequent screening with longer intervals between screening than the 5-year interval currently recommended was consistently preferred at the threshold of $55 000 per QALY, but the preferred strategy varied by age at vaccination. For women vaccinated between ages 12 and 24 years, preferred strategies involved screening every 15 to 25 years, resulting in screening 2 to 3 times per lifetime. Less frequent screening remained a preferred strategy under imperfect screening adherence and in scenarios that excluded bivalent vaccine cross-protection. The analysis did not address screening for unvaccinated women, who may benefit from herd immunity. A high-value screening program likely involves less frequent screening for women who were vaccinated against HPV by age 30 years. Strategies could be tailored on the basis of age at vaccination and type of HPV vaccine. Norwegian Cancer Society and National Cancer Institute.

Background: Reliable estimates of immunization delivery costs are essential for planning, budgeting, and economic evaluation. Despite recent empirical studies, many low- and middle-income countries (LMICs) lack up-to-date cost estimates, particularly for adolescent and campaign vaccination. This study generated standardized country-level delivery cost estimates across vaccination modalities in LMICs. Methods: Using data from empirical costing studies in the 2024 update of the Immunization Delivery Cost Catalogue, we fitted Bayesian meta-regression models to estimate per-dose delivery costs, not including vaccine and injection supplies costs, for routine childhood vaccination, routine adolescent vaccination (using human papillomavirus vaccination as a proxy), and mass campaigns. Models incorporated country-level covariates (gross domestic product per capita, population size, diphtheria-tetanus-pertussis third-dose coverage, urbanization, population density, and under-five mortality) and study-level characteristics (cost category and costing perspective). Fitted models were used to generate country-specific and population-weighted mean economic and financial costs per dose in 2024 US dollars. Results: The analysis included 141 observations for routine childhood, 49 for adolescent, and 104 for campaign vaccination. The population-weighted mean full economic cost per dose across LMICs was $4.27 (95% prediction interval: $1.95–11.58) for routine childhood vaccination, $20.56 ($8.56–57.83) for adolescent vaccination, and $14.71 ($4.90–86.98) for campaigns. Corresponding estimates for incremental economic costs per dose were $16.64 ($7.90–38.22), $20.43 ($8.27–47.78), and $3.53 ($1.70–8.56). Substantial heterogeneity was observed across countries, delivery modalities, and cost perspectives. Conclusions: Leveraging an expanded evidence-base and Bayesian meta-regression, this study provides updated delivery cost estimates across vaccination modalities for 136 LMICs. These estimates offer a practical resource for analyses where empirical cost data are unavailable. Key points: This study provides updated estimates of how much it costs to deliver vaccines across low- and middle-income countries, showing that costs vary widely depending on how vaccines are delivered and the context of each country. On average, delivering vaccines to adolescents (facility-based, school-based, and outreach) is substantially more expensive than routine childhood vaccination, while campaign delivery costs fall in between, reflecting differences in logistics and delivery strategies. These results offer practical, comparable cost benchmarks that policymakers and researchers can use to plan immunization programs and make informed decisions when country-specific data are not available.

Purpose: Sexual transmission of human papillomavirus (HPV) infection is important for capturing the indirect effects of interventions in mathematical models, but limited data create challenges for reflecting sexual behavior patterns over the lifespan of individuals and across heterogenous populations. We used nationally representative data from the United States to parameterize, calibrate, and validate a heterosexual transmission model of HPV. Methods: Based on sexual behavior data from the National Survey of Family Growth (2011–2019), we categorized respondents into 4 sexual activity categories, using their percentile of cumulative lifetime partners compared with others within their same sex and age group. We modeled probabilistic partnership acquisition and dissolution by age, sex, and sexual activity category. Partnership data were incorporated into an existing agent-based model of HPV transmission in the United States. We calibrated 1) per-partnership HPV transmission and 2) reduced risk of type-specific reinfection from natural immunity to fit age- and type-specific HPV prevalence using the National Health and Nutrition Examination Survey (NHANES 2002–2008). We validated the final model by comparing model-based projections of HPV prevalence against empirical data in the US population before and after widespread HPV vaccination. Results: After calibrating to fit overall HPV prevalence, model validation exercises indicated that the distribution of prevaccine HPV prevalence across sexual activity categories closely matched NHANES estimates. Simulating vaccination rates over 10 y, the model replicated postvaccine NHANES data for prevalence of HPV16. Conclusion: Capturing HPV transmission dynamics requires an understanding of sexual behavior across populations and over time. Defining sexual activity categories based on cumulative lifetime partners can capture patterns of HPV risk over a lifespan to reflect the dynamics of HPV transmission and vaccination. Highlights: Using data from a large national survey, we developed sexual behavior inputs for an agent-based model of HPV transmission. We define 4 heterogenous risk groups using cumulative lifetime sexual behavior for males and females and find we can recreate validation data on both lifetime sexual patterns and age-specific HPV prevalence. Our calibrated model also reproduces early patterns of HPV reduction following HPV vaccine introduction. Modelers seeking to understand the long-term effects of the HPV vaccine should carefully consider the heterogeneity of sexual behavior across groups as well as changes in behavior over the lifespan.

Background: Recent shifts in the global health funding landscape—most notably the dismantling of the United States Agency for International Development (USAID) and possible reduced contributions to the Global Fund to Fight AIDS, TB, and Malaria (Global Fund)—threaten essential tuberculosis (TB) services in low- and middle-income countries (LMICs). We quantified the potential impact on the household economic burden of TB. Methods and findings: We used linked epidemiological and economic models, calibrated to 79 LMICs, to estimate future TB patient costs under six scenarios: continuation of 2024 funding levels (baseline), termination of USAID, termination of USAID plus announced reductions in Global Fund contributions from the USA alone, termination of USAID plus complete termination of Global Fund contributions from the USA alone, termination of USAID plus announced reductions in Global Fund contributions from all donor countries contributing 1% or more to the budget, and full elimination of external funding for TB. Outcomes included total TB-attributable household costs and numbers of households experiencing catastrophic costs (disease-related costs >20% of annual income). USAID termination was projected to produce US$7.5 (95% uncertainty interval: $6.1–8.9) billion in additional patient-incurred costs and 3.9 (3.1–4.6) million additional households experiencing catastrophic costs over 2025–2050. The worst-case scenario (elimination of all external funding) resulted in $79.7 ($60.0–99.2) billion in additional patient-incurred costs and 40.5 (30.9–50.7) million additional households experiencing catastrophic costs—a 32% increase over baseline. Impacts were greatest for poorer households, with over 50% of additional catastrophic costs occurring in the poorest 20% of households. This analysis is limited by substantial uncertainty regarding costs faced by untreated patients and assumptions of constant patient costs and uniform treatment reductions over time. Conclusions: Abrupt reductions in international donor funding for TB may reverse recent progress toward financial risk protection and health equity in LMICs. Strategies to reduce the disruption caused by funding cuts and protect vulnerable populations are urgently needed.