Allison Portnoy

Population-level health impact of hypothetical waning 1-dose human papillomavirus vaccination and 2-dose mitigation strategies in a high cervical cancer burden setting

Abstract Background We simulated the impact of hypothetical waning scenarios of a 1-dose human papillomavirus (HPV) vaccination paired with switching to 2-dose mitigation strategies guided by empirical vaccine trial reporting timelines. Methods Using 2 independent mathematical models fitted to a high-burden setting, we projected the cumulative cervical cancer cases averted over 85 years for alternative HPV vaccination scenarios under 2 program adoption timelines: 1) de novo introduction of a 1-dose HPV vaccination and 2) a switch from an existing 2-dose HPV vaccination program to a 1-dose vaccination. We assumed 80% vaccination coverage with the bivalent vaccine and an average duration of a 1-dose HPV vaccine protection of either 30 or 25 years with 100% efficacy. We varied the eligible age group(s) at program introduction and the 2-dose mitigation (single-age cohort or multi-age cohort). If needed for mitigation, reintroduction of 2-dose vaccination was assumed to occur in 2036 (ie, 30 years after initiation of the Costa Rica Vaccine Trial). Results Under both vaccine adoption timelines, the models projected that countries could achieve the same level of health benefits by switching to 2 doses in 2036 using a multi-age cohort approach as with initiating a 2-dose or 1-dose vaccination program with no waning. With only a single-age cohort 2-dose mitigation approach, 98%-99% of cases would be prevented compared with the health benefits of 2 doses or a noninferior, durable 1 dose. Conclusions Countries hesitant to adopt a 1-dose HPV vaccination program may have opportunities to leverage the benefits and efficiency of a 1-dose schedule while awaiting longer-term reporting from 1-dose durability studies, including Costa Rica Vaccine Trial.

Vaccination and screening strategies to accelerate cervical cancer elimination in Norway: a model-based analysis

Experts have proposed an 'EVEN FASTER' concept targeting age-groups maintaining circulation of human papillomavirus (HPV). We explored effects of the vaccination component of these proposals compared with cervical cancer (CC) screening-based interventions on age-standardized incidence rate (ASR) and CC elimination (<4 cases/100,000) timing in Norway. We used a model-based approach to evaluate HPV vaccination and CC screening scenarios compared with a status-quo scenario reflecting previous vaccination and screening. For cohorts ages 25-30 years, we examined 6 vaccination scenarios that incrementally increased vaccination coverage from current cohort-specific rates. Each vaccination scenario was coupled with three screening strategies that varied screening frequency. Additionally, we included 4 scenarios that alternatively increased screening adherence. Population- and cohort-level outcomes included ASR, lifetime risk of CC, and colposcopy referrals. Several vaccination strategies coupled with de-intensified screening frequencies lowered ASR, but did not accelerate CC elimination. Alternative strategies that increased screening adherence could both accelerate elimination and improve ASR. The vaccination component of an 'EVEN FASTER' campaign is unlikely to accelerate CC elimination in Norway but may reduce population-level ASR. Alternatively, targeting under- and never-screeners may both eliminate CC faster and lead to greater health benefits compared with vaccination-based interventions we considered.

Choosing the optimal HPV vaccine: The health impact and economic value of the nonavalent and bivalent HPV vaccines in 48 Gavi‐eligible countries

AbstractThe human papillomavirus (HPV) vaccines may provide some level of cross‐protection against high‐risk HPV genotypes not directly targeted by the vaccines. We evaluated the long‐term health and economic impacts of routine HPV vaccination using either the nonavalent HPV vaccine or the bivalent HPV vaccine in the context of 48 Gavi‐eligible countries. We used a multi‐modeling approach to compare the bivalent with or without cross‐protection and the nonavalent HPV vaccine. The optimal, that is, most cost‐effective, vaccine was the vaccine with an incremental cost‐effectiveness ratio below the per‐capita gross domestic product (GDP) for each country. By 2100 and assuming 70% HPV vaccination coverage, a bivalent vaccine without cross‐protection, a bivalent vaccine with favorable cross‐protection and the nonavalent vaccine were projected to avert 14.9, 17.2 and 18.5 million cumulative cases of cervical cancer across all 48 Gavi‐eligible countries, respectively. The relative value of the bivalent vaccine compared to the nonavalent vaccine increased assuming a bivalent vaccine conferred high cross‐protection. For example, assuming a cost‐effectiveness threshold of per‐capita GDP, the nonavalent vaccine was optimal in 83% (n = 40) of countries if the bivalent vaccine did not confer cross‐protection; however, the proportion of countries decreased to 63% (n = 30) if the bivalent vaccine conferred high cross‐protection. For lower cost‐effectiveness thresholds, the bivalent vaccine was optimal in a greater proportion of countries, under both cross‐protection assumptions. Although the nonavalent vaccine is projected to avert more cases of cervical cancer, the bivalent vaccine with favorable cross‐protection can prevent a considerable number of cases and would be considered a high‐value vaccine for many Gavi‐eligible countries.

The impact of vaccination on gender equity: conceptual framework and human papillomavirus (HPV) vaccine case study

Abstract Background Although the beneficial effects of vaccines on equity by socioeconomic status and geography are increasingly well-documented, little has been done to extend these analyses to examine the linkage between vaccination and gender equity. In this paper, evidence from the published literature is used to develop a conceptual framework demonstrating the potential impact of vaccination on measures of gender equity. This framework is then applied to human papillomavirus (HPV) vaccination in three countries with different economic and disease burden profiles to establish a proof of concept in a variety of contexts. Methods We conducted a literature review examining evidence on the linkage between health outcomes and dimensions of gender equity. We utilized the Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model to estimate cervical cancer incidence and deaths due to HPV types 16/18 by age in each country. We estimated labor force participation and fertility effects from improvements in health, and converted these into inputs consistent with those used to calculate the United Nations Gender Inequality Index to assess gender equity. Results In our case study, we found that HPV vaccination among girls could help narrow socioeconomic gender disparities by quantifying the main pathways by which HPV vaccination improves health, which enables improvement in gender equity indicators such as labor force participation and maternal mortality ratios. While these improvements are small when averaged over the entire population, the components measured – labor force participation and maternal mortality ratio – account for 50% of the index scores. Conclusions This proof of concept model is a starting point to inform future health and economic analyses that might incorporate the impact of gender equity as an additional impact of vaccination in improving the health and well-being of the population.

Switching clinic‐based cervical cancer screening programs to human papillomavirus self‐sampling: A cost‐effectiveness analysis of vaccinated and unvaccinated Norwegian women

AbstractSeveral countries have implemented primary human papillomavirus (HPV) testing for cervical cancer screening. HPV testing enables home‐based, self‐collected sampling (self‐sampling), which provides similar diagnostic accuracy as clinician‐collected samples. We evaluated the impact and cost‐effectiveness of switching an entire organized screening program to primary HPV self‐sampling among cohorts of HPV vaccinated and unvaccinated Norwegian women. We conducted a model‐based analysis to project long‐term health and economic outcomes for birth cohorts with different HPV vaccine exposure, that is, preadolescent vaccination (2000‐ and 2008‐cohorts), multiage cohort vaccination (1991‐cohort) or no vaccination (1985‐cohort). We compared the cost‐effectiveness of switching current guidelines with clinician‐collected HPV testing to HPV self‐sampling for these cohorts and considered an additional 44 strategies involving either HPV self‐sampling or clinician‐collected HPV testing at different screening frequencies for the 2000‐ and 2008‐cohorts. Given Norwegian benchmarks for cost‐effectiveness, we considered a strategy with an additional cost per quality‐adjusted life‐year below $55 000 as cost‐effective. HPV self‐sampling strategies considerably reduced screening costs (ie, by 24%‐40% across cohorts and alternative strategies) and were more cost‐effective than clinician‐collected HPV testing. For cohorts offered preadolescent vaccination, cost‐effective strategies involved HPV self‐sampling three times (2000‐cohort) and twice (2008‐cohort) per lifetime. In conclusion, we found that switching from clinician‐collected to self‐collected HPV testing in cervical screening may be cost‐effective among both highly vaccinated and unvaccinated cohorts of Norwegian women.

Health gains and financial protection from human papillomavirus vaccination in Ethiopia: findings from a modelling study

AbstractHigh out-of-pocket (OOP) medical expenses for cervical cancer (CC) can lead to catastrophic health expenditures (CHEs) and medical impoverishment in many low-resource settings. There are 32 million women at risk for CC in Ethiopia, where CC screening is extremely limited. An evaluation of the population health and financial risk protection benefits, and their distributional consequences across socioeconomic groups, from human papillomavirus (HPV) vaccination will be critical to support CC prevention efforts in this setting. We used a static cohort model that captures the main features of HPV vaccines and population demographics to project health and economic outcomes associated with routine HPV vaccination in Ethiopia. Health outcomes included the number of CC cases, and costs included vaccination and operational costs in 2015 US dollars over the years 2019–2118 and CC treatment costs over the lifetimes of cohorts eligible for vaccination in Ethiopia. We estimated the household OOP medical expenditures averted (assuming 68% of direct medical expenditures were financed OOP) and cases of CHE averted. A case of CHE was defined as 40% of household consumption expenditures, and the cases of CHE averted depended on wealth quintile, disease incidence, healthcare use and OOP payments. Our analysis shows that, assuming 100% vaccine efficacy against HPV-16/18 and 50% vaccination coverage, routine HPV vaccination could avert up to 970 000 cases of CC between 2019 and 2118, which translates to ∼932 000 lives saved. Additionally, routine HPV vaccination could avert 33 900 cases of CHE. Approximately one-third of health benefits would accrue to the poorest wealth quintile, whereas 50% of financial risk protection benefits would accrue to this quintile. HPV vaccination can reduce disparities in CC incidence, mortality and household health expenditures. This understanding and our findings can help policymakers in decisions regarding targeted CC control efforts and investment in a routine HPV vaccination programme following an initial catch-up programme.

Identifying a Single Optimal Integrated Cervical Cancer Prevention Policy in Norway: A Cost-Effectiveness Analysis

Background Interventions targeting the same disease but at different points along the disease continuum (e.g., screening and vaccination to prevent cervical cancer [CC]) are often evaluated in isolation, which can affect cost-effectiveness profiles and policy conclusions. We evaluated nonavalent human papillomavirus (HPV) vaccine (9vHPV) compared with bivalent HPV vaccine (2vHPV) alongside deintensified screening intervals for a vaccinated birth cohort to inform a single optimal integrated CC prevention policy. Methods Using a multimodeling approach, we evaluated the health and economic impacts of alternative CC screening strategies for a Norwegian birth cohort eligible for HPV vaccination in 2021 assuming they received 1) 2vHPV or 2) 9vHPV. We conducted 1) a restricted analysis that evaluated the optimal HPV vaccine under current screening guidelines; and 2) a comprehensive analysis including alternative screening and vaccination strategy combinations. We calculated incremental cost-effectiveness ratios (ICERs) and evaluated them according to different cost-effectiveness thresholds. Results Assuming a cost-effectiveness threshold of $40,000 per quality-adjusted life year (QALY) gained, we found that, while holding screening intensity fixed, switching the routine vaccination program in Norway from 2vHPV to 9vHPV would not be considered cost-effective (ICER of $132,700 per QALY gained). However, when allowing for varying intensities of CC screening, we found that switching to 9vHPV would be cost-effective compared with 2vHPV under an alternative threshold of $55,000 per QALY gained, if coupled with reductions in the number of lifetime screens. Conclusions Our analysis highlights the importance of evaluating the full potential policy landscape for country-level decision makers considering policy adoption, including nonindependent primary and secondary prevention efforts, to draw appropriate conclusions and avoid sub-optimal outcomes. Highlights Without evaluating the full potential policy landscape, including primary and secondary prevention efforts, country-level decision makers may not be able to draw appropriate policy conclusions, resulting in suboptimal outcomes. An applied example from cervical cancer prevention in Norway compared a restricted analysis of current screening guidelines to a comprehensive analysis including alternative screening and vaccination strategy combinations. We found that a switch from bivalent to nonavalent human papillomavirus vaccine would be considered cost-effective in Norway if coupled with reductions in the number of lifetime screens compared with the current screening strategy. A comprehensive analysis that considers how different types of interventions along the disease continuum affect each other will be critical for decision makers interpreting cost-effectiveness analysis results.

Cost‐effectiveness of primary human papillomavirus triage approaches among vaccinated women in Norway: A model‐based analysis

AbstractAs Norway considers revising triage approaches following their first adolescent cohort with human papillomavirus (HPV) vaccination entering the cervical cancer screening program, we analyzed the health impact and cost‐effectiveness of alternative primary HPV triage approaches for women initiating cervical cancer screening in 2023. We used a multimodeling approach that captured HPV transmission and cervical carcinogenesis to evaluate the health benefits, harms and cost‐effectiveness of alternative extended genotyping and age‐based triage strategies under five‐yearly primary HPV testing (including the status‐quo screening strategy in Norway) for women born in 1998 (ie, age 25 in 2023). We examined 35 strategies that varied alternative groupings of high‐risk HPV genotypes (“high‐risk” genotypes; “medium‐risk” genotypes or “intermediate‐risk” genotypes), number and types of HPV included in each group, management of HPV‐positive women to direct colposcopy or active surveillance, wait time for re‐testing and age at which the HPV triage algorithm switched from less to more intensive strategies. Given the range of benchmarks for severity‐specific cost‐effectiveness thresholds in Norway, we found that the preferred strategy for vaccinated women aged 25 years in 2023 involved an age‐based switch from a less to more intensive follow‐up algorithm at age 30 or 35 years with HPV‐16/18 genotypes in the “high‐risk” group. The two potentially cost‐effective strategies could reduce the number of colposcopies compared to current guidelines and simultaneously improve health benefits. Using age to guide primary HPV triage, paired with selective HPV genotype and follow‐up time for re‐testing, could improve both the cervical cancer program effectiveness and efficiency.