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

As 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.

Adapting a model of cervical carcinogenesis to self-identified Black women to evaluate racial disparities in the United States.

BACKGROUND: Self-identified Black women in the United States have higher cervical cancer incidence and mortality than the general population, but these differences have not been clearly attributed across described cancer care inequities. METHODS: A previously established microsimulation model of cervical cancer was adapted to reflect demographic, screening, and survival data for Black US women and compared with a model reflecting data for all US women. Each model input with stratified data (all-cause mortality, hysterectomy rates, screening frequency, screening modality, follow-up, and cancer survival) was sequentially replaced with Black-race specific data to arrive at a fully specified model reflecting Black women. At each step, we estimated the relative contribution of inputs to observed disparities. RESULTS: Estimated (hysterectomy-adjusted) cervical cancer incidence was 8.6 per 100 000 in the all-race model vs 10.8 per 100 000 in the Black-race model (relative risk [RR] = 1.24, range = 1.23-1.27). Estimated all-race cervical cancer mortality was 2.9 per 100 000 vs 5.5 per 100 000 in the Black-race model (RR = 1.92, range = 1.85-2.00). We found the largest contributors of incidence disparities were follow-up from positive screening results (47.3% of the total disparity) and screening frequency (32.7%). For mortality disparities, the largest contributor was cancer survival differences (70.1%) followed by screening follow-up (12.7%). CONCLUSION: To reduce disparities in cervical cancer incidence and mortality, it is important to understand and address differences in care access and quality across the continuum of care. Focusing on the practices and policies that drive differences in treatment and follow-up from cervical abnormalities may have the highest impact.

Global impact and cost-effectiveness of one-dose versus two-dose human papillomavirus vaccination schedules: a comparative modelling analysis.

BACKGROUND: To eliminate cervical cancer as a public health problem, the World Health Organization had recommended routine vaccination of adolescent girls with two doses of the human papillomavirus (HPV) vaccine before sexual initiation. However, many countries have yet to implement HPV vaccination because of financial or logistical barriers to delivering two doses outside the infant immunisation programme. METHODS: Using three independent HPV transmission models, we estimated the long-term health benefits and cost-effectiveness of one-dose versus two-dose HPV vaccination, in 188 countries, under scenarios in which one dose of the vaccine gives either a shorter duration of full protection (20 or 30 years) or lifelong protection but lower vaccine efficacy (e.g. 80%) compared to two doses. We simulated routine vaccination with the 9-valent HPV vaccine in 10-year-old girls at 80% coverage for the years 2021-2120, with a 1-year catch-up campaign up to age 14 at 80% coverage in the first year of the programme. RESULTS: Over the years 2021-2120, one-dose vaccination at 80% coverage was projected to avert 115.2 million (range of medians: 85.1-130.4) and 146.8 million (114.1-161.6) cervical cancers assuming one dose of the vaccine confers 20 and 30 years of protection, respectively. Should one dose of the vaccine provide lifelong protection at 80% vaccine efficacy, 147.8 million (140.6-169.7) cervical cancer cases could be prevented. If protection wanes after 20 years, 65 to 889 additional girls would need to be vaccinated with the second dose to prevent one cervical cancer, depending on the epidemiological profiles of the country. Across all income groups, the threshold cost for the second dose was low: from 1.59 (0.14-3.82) USD in low-income countries to 44.83 (3.75-85.64) USD in high-income countries, assuming one dose confers 30-year protection. CONCLUSIONS: Results were consistent across the three independent models and suggest that one-dose vaccination has similar health benefits to a two-dose programme while simplifying vaccine delivery, reducing costs, and alleviating vaccine supply constraints. The second dose may become cost-effective if there is a shorter duration of protection from one dose, cheaper vaccine and vaccination delivery strategies, and high burden of cervical cancer.

Designing Guidelines for Those Who Do Not Follow Them: The Impact of Adherence Assumptions on Optimal Screening Guidelines.

OBJECTIVES: Model-based cost-effectiveness analyses can inform decisions about screening guidelines by quantifying consequences of alternative algorithms. Although actual screening adherence is imperfect, incorporating nonadherence into analyses that aim to determine optimal screening may affect the policy recommendations. We evaluated the impact of nonadherence assumptions on the optimal cervical cancer screening in Norway. METHODS: We used a microsimulation model of cervical carcinogenesis to project the long-term health and economic outcomes under alternative screening algorithms and adherence patterns. We compared 18 algorithms involving primary human papillomavirus testing (5-yearly) that varied follow-up management of different human papillomavirus results. We considered 12 adherence scenarios: perfect adherence, 8 high- and low-coverage "random-complier" scenarios, and 3 "systematic-complier" scenarios that reflect conditional screening behavior over a lifetime. We calculated incremental cost-effectiveness ratios and considered a strategy with the highest incremental cost-effectiveness ratio < 55 000 US dollars/quality-adjusted life-year as "optimal." RESULTS: Under perfect adherence, the least intensive screening strategy was optimal; in contrast, assuming any nonadherence resulted in a more intensive optimal strategy. Accounting for lower adherence resulted in both lower costs and health benefits, which allowed for a more intensive strategy to be considered optimal, but more harms for women who screen according to guidelines (ie, up to 41% more colposcopies when comparing the optimal strategy in the lowest-adherence scenario with the optimal strategy under perfect adherence). CONCLUSIONS: Assuming nonadherence in analyses designed to inform national guidelines may lead to a relatively more intensive recommendation. Designing guidelines for those who do not adhere to them may lead to over-screening of those who do.

Upper age limits for US male human papillomavirus vaccination for oropharyngeal cancer prevention: a microsimulation-based modeling study.

BACKGROUND: Human papillomavirus (HVP)-positive oropharyngeal cancer is the most common HPV-associated cancer in the United States. The age at acquisition of oral HPV infections that cause oropharyngeal cancer (causal infections) is unknown; consequently, the benefit of vaccination of US men aged 27-45 years remains uncertain. METHODS: We developed a microsimulation-based, individual-level, state-transition model of oral HPV16 and HPV16-positive oropharyngeal cancer among heterosexual US men aged 15-84 years, calibrated to population-level data. We estimated the benefit of vaccination of men aged 27-45 years for prevention of oropharyngeal cancer, accounting for direct- and indirect effects (ie, herd effects) of male and female vaccination. RESULTS: In the absence of vaccination, most (70%) causal oral HPV16 infections are acquired by age 26 years, and 29% are acquired between ages 27 and 45 years. Among men aged 15-45 years in 2021 (1976-2006 birth cohorts), status quo vaccination of men through age 26 years is estimated to prevent 95% of 153 450 vaccine-preventable cancers. Assuming 100% vaccination in 2021, extending the upper age limit to 30, 35, 40, or 45 years for men aged 27-45 years (1976-1994 cohorts) is estimated to yield small benefits (3.0%, 4.2%, 5.1%, and 5.6% additional cancers prevented, respectively). Importantly, status quo vaccination of men through age 26 years is predicted to result in notable declines in HPV16-positive oropharyngeal cancer incidence in young men by 2035 (51% and 24% declines at ages 40-44 years and 45-49 years, respectively) and noticeable declines (12%) overall by 2045. CONCLUSION: Most causal oral HPV16 infections in US men are acquired by age 26 years, underscoring limited benefit from vaccination of men aged 27-45 years for prevention of HPV16-positive oropharyngeal cancers.

Now or later: Health impacts of delaying single-dose HPV vaccine implementation in a high-burden setting.

We aimed to quantify the health impact of immediate introduction of a single-dose human papillomavirus (HPV) vaccination program in a high-burden setting, as waiting until forthcoming trials are completed to implement single-dose HPV vaccination may result in health losses, particularly for cohorts who would age-out of vaccination eligibility. Two mathematical models fitted to a high-burden setting projected cervical cancer incidence rates associated with (a) immediate implementation of one-dose HPV vaccination vs (b) waiting 5 years for evidence from randomized trials to determine if one- or two-doses should be implemented. We conducted analyses assuming a single dose was either noninferior or inferior to two doses. The models projected that immediate implementation of a noninferior single-dose vaccine led to a 7.2% to 9.6% increase in cancers averted between 2021 to 2120, compared to waiting 5 years. Health benefits remained greater with immediate implementation despite an inferior single-dose efficacy (80%), but revaccination of one-dose recipients became more important assuming vaccine waning. Under most circumstances, immediate vaccination avoided health losses for those aging out of vaccine eligibility, leading to greater health benefits than waiting for more information in 5 years.

Implementing federal food service guidelines in federal and private worksite cafeterias in the United States leads to improved health outcomes and is cost saving.

Poor diet increases cardiometabolic disease risk, yet the impact of food service guidelines on employee health and its cost effectiveness is poorly understood. Federal food service guidelines (FFSG) aim to provide United States (U.S.) government employees with healthier food options. Using microsimulation modeling, we estimated changes in the incidence of cardiometabolic disease, related mortality, and the cost effectiveness of implementing FFSG in nationally representative model populations of government and private company employees across 5 years and lifetime. We based estimates on changes in workplace intake of six FFSG dietary targets and showed lifetime reductions of heart attacks (- 107/million), strokes (- 30/million), diabetes (- 134/million), ischemic heart disease deaths (- 56/million), and stroke deaths (- 8/million). FFSG is cost saving overall, with total savings in discounted healthcare costs from $4,611,026 (5 years) to $539,809,707 (lifetime) $U.S. This study demonstrates that FFSG improves health outcomes and is cost saving.

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

Several 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.

Potential effectiveness of a therapeutic HPV intervention campaign in Uganda.

Cervical cancer is a major source of morbidity and mortality in Uganda. In addition to prophylactic HPV vaccination, secondary prevention strategies are needed to reduce cancer burden. We evaluated the potential cancer reductions associated with a hypothetical single-contact therapeutic HPV intervention-with 70% coverage and variable efficacy [30%-100%]-using a three-stage HPV modeling framework reflecting HPV and cervical cancer burden in Uganda. In the reference case, we assumed prophylactic preadolescent HPV vaccination starting in 2020 with 70% coverage. A one-time therapeutic intervention targeting 35-year-old women in 2025 (not age-eligible for prophylactic vaccination) averted 1801 cervical cancers per 100 000 women over their lifetime (100% efficacy) or 533 cancers per 100 000 (30% efficacy). Benefits were considerably smaller in birth cohorts eligible for prophylactic HPV vaccination (768 cases averted per 100 000 at 100% efficacy). Evaluating the population-level impact over 40 years, we found introduction of a therapeutic intervention in 2025 with 100% efficacy targeted annually to 30-year-old women averted 139 000 incident cervical cancers in Uganda. This benefit was greatly reduced if efficacy was lower (30% efficacy; 41 000 cases averted), introduction was delayed (2040 introduction; 72 000 cases averted) or both (22 000 cases averted). We demonstrate the potential benefits of a single-contact HPV therapeutic intervention in a low-income setting, but show the importance of high therapeutic efficacy and early introduction timing relative to existing prophylactic programs. Reduced benefits from a less efficacious intervention may be somewhat offset if available within a shorter time frame.

Cost-effectiveness analysis of the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines for the management of abnormal cervical cancer screening tests and cancer precursors.

BACKGROUND: The guidelines for managing abnormal cervical cancer screening tests changed from a results-based approach in 2012 to a risk-based approach in 2019. OBJECTIVE: We estimated the cost-effectiveness of the 2019 management guidelines and the changes in resource utilization moving from 2012 to 2019 guidelines. STUDY DESIGN: We utilized a previously published model of cervical cancer natural history and screening to estimate and compare the lifetime costs and the number of screens, colposcopies, precancer treatments, cancer cases, and cancer deaths associated with the 2012 vs 2019 management guidelines. We assessed these guidelines under the scenarios of observed screening practice and perfect screening adherence to 3-year cytology starting at age 21, with a switch to either 3-year or 5-year cytology plus human papillomavirus cotesting at age 30. In addition, we estimated the lifetime costs and life years to determine the cost-effectiveness of shifting to the 2019 management guidelines. RESULTS: Under the assumptions of both observed screening practice and perfect screening adherence with a strategy of 3-year cytology at ages 21 to 29 and switching to 3-year cotesting at age 30, the management of the screening tests according to the 2019 guidelines was less costly and more effective than the 2012 guidelines. For 3-year cytology screening at ages 21 to 29 and switching to 5-year cotesting at age 30, the 2019 guidelines were more cost-effective at a willingness-to-pay threshold of $100,000 per life year gained. Across all scenarios, the 2019 management guidelines were associated with fewer colposcopies and cancer deaths. CONCLUSION: Our model-based analysis suggests that the 2019 guidelines are more effective overall and also more cost-effective than the 2012 guidelines, supporting the principle of "equal management of equal risks."

Health Impact and Cost-Effectiveness of Achieving the National Salt and Sugar Reduction Initiative Voluntary Sugar Reduction Targets in the United States: A Microsimulation Study.

BACKGROUND: High intake of added sugar is linked to weight gain and cardiometabolic risk. In 2018, the US National Salt and Sugar Reduction Initiative proposed government-supported voluntary national sugar reduction targets. This intervention's potential effects and cost-effectiveness are unclear. METHODS: A validated microsimulation model, CVD-PREDICT (Cardiovascular Disease Policy Model for Risk, Events, Detection, Interventions, Costs, and Trends), coded in C++, was used to estimate incremental changes in type 2 diabetes, cardiovascular disease (CVD), quality-adjusted life-years (QALYs), costs, and cost-effectiveness of the US National Salt and Sugar Reduction Initiative policy. The model was run at the individual level, incorporating the annual probability of each person's transition between health statuses on the basis of risk factors. The model incorporated national demographic and dietary data from the National Health and Nutrition Examination Survey across 3 cycles (2011 through 2016), added sugar-related diseases from meta-analyses, and policy costs and health-related costs from established sources. A simulated nationally representative US population was created and followed until age 100 years or death, with 2019 as the year of intervention start. Findings were evaluated over 10 years and a lifetime from health care and societal perspectives. Uncertainty was evaluated in a 1-way analysis by assuming 50% industry compliance and probabilistic sensitivity analyses through a second-order Monte Carlo approach. Model outputs included averted diabetes cases, CVD events and CVD deaths, QALYs gained, and formal health care cost savings, stratified by age, race, income, and education. RESULTS: Achieving the US National Salt and Sugar Reduction Initiative sugar reduction targets could prevent 2.48 million CVD events, 0.49 million CVD deaths, and 0.75 million diabetes cases; gain 6.67 million QALYs; and save $160.88 billion net costs from a societal perspective over a lifetime. The policy became cost-effective (<150 000/QALYs) at 6 years, highly cost-effective (<50 000/QALYs) at 7 years, and cost-saving at 9 years. Results were robust from a health care perspective, with lower (50%) industry compliance, and in probabilistic sensitivity analyses. The policy could also reduce disparities, with greatest estimated health gains per million adults among Black or Hispanic individuals, lower income, and less educated Americans. CONCLUSIONS: Implementing and achieving the US National Salt and Sugar Reduction Initiative sugar reformation targets could generate substantial health gains, equity gains, and cost savings.

Cost-Effectiveness of Offering Cervical Cancer Screening with HPV Self-Sampling among African-American Women in the Mississippi Delta.

BACKGROUND: African-American women in the United States have an elevated risk of cervical cancer incidence and mortality. In the Mississippi Delta, cervical cancer disparities are particularly stark. METHODS: We conducted a micro-costing study alongside a group randomized trial that evaluated the efficacy of a patient-centered approach ("Choice" between self-collection at home for HPV testing or current standard of care within the public health system in Mississippi) versus the current standard of care ["Standard-of-care screening," involving cytology (i.e., Pap) and HPV co-testing at the Health Department clinics]. The interventions in both study arms were delivered by community health workers (CHW). Using cost, screening uptake, and colposcopy adherence data from the trial, we informed a mathematical model of HPV infection and cervical carcinogenesis to conduct a cost-effectiveness analysis comparing the "Choice" and "Standard-of-care screening" interventions among un/underscreened African-American women in the Mississippi Delta. RESULTS: When each intervention was simulated every 5 years from ages 25 to 65 years, the "Standard-of-care screening" strategy reduced cancer risk by 6.4% and was not an efficient strategy; "Choice" was more effective and efficient, reducing lifetime risk of cervical cancer by 14.8% and costing $62,720 per year of life saved (YLS). Screening uptake and colposcopy adherence were key drivers of intervention cost-effectiveness. CONCLUSIONS: Offering "Choice" to un/underscreened African-American women in the Mississippi Delta led to greater uptake than CHW-facilitated screening at the Health Department, and may be cost-effective. IMPACT: We evaluated the cost-effectiveness of an HPV self-collection intervention to reduce disparities.

Impact and cost-effectiveness of strategies to accelerate cervical cancer elimination: A model-based analysis.

Following the global call for action by the World Health Organization to eliminate cervical cancer (CC), we evaluated how each CC policy decision in Norway influenced the timing of CC elimination, and whether introducing nonavalent human papillomavirus (HPV) vaccine would accelerate elimination timing and be cost-effective. We used a multi-modeling approach that captured HPV transmission and cervical carcinogenesis to estimate the CC incidence associated with six past and future CC prevention policy decisions compared with a pre-vaccination scenario involving 3-yearly cytology-based screening. Scenarios examined the introduction of routine HPV vaccination of 12-year-old girls with quadrivalent vaccine in 2009, a temporary catch-up program for females aged up to 26 years in 2016-2018 with bivalent vaccine, the universal switch to bivalent vaccine in 2017, expansion to include 12-year-old boys in 2018, the switch from cytology- to HPV-based screening for women aged 34-69 in 2020, and the potential switch to nonavalent vaccine in 2021. Introducing routine female vaccination in 2009 enabled elimination to be achieved by 2056 and prevented 17,300 cases. Cumulatively, subsequent policy decisions accelerated elimination to 2039. According to our modeling assumptions, switching to the nonavalent vaccine would not be considered 'good value for money' at relevant cost-effectiveness thresholds in Norway unless the incremental cost was $19 per dose or less (range: $17-24) compared to the bivalent vaccine. CC control policies implemented over the last decade in Norway may have accelerated the timeframe to elimination by more than 17 years and prevented over 23,800 cases by 2110.

Human papillomavirus vaccination for adults aged 30 to 45 years in the United States: A cost-effectiveness analysis.

BACKGROUND: A nonavalent human papillomavirus (HPV) vaccine has been licensed for use in women and men up to age 45 years in the United States. The cost-effectiveness of HPV vaccination for women and men aged 30 to 45 years in the context of cervical cancer screening practice was evaluated to inform national guidelines. METHODS AND FINDINGS: We utilized 2 independent HPV microsimulation models to evaluate the cost-effectiveness of extending the upper age limit of HPV vaccination in women (from age 26 years) and men (from age 21 years) up to age 30, 35, 40, or 45 years. The models were empirically calibrated to reflect the burden of HPV and related cancers in the US population and used standardized inputs regarding historical and future vaccination uptake, vaccine efficacy, cervical cancer screening, and costs. Disease outcomes included cervical, anal, oropharyngeal, vulvar, vaginal, and penile cancers, as well as genital warts. Both models projected higher costs and greater health benefits as the upper age limit of HPV vaccination increased. Strategies of vaccinating females and males up to ages 30, 35, and 40 years were found to be less cost-effective than vaccinating up to age 45 years, which had an incremental cost-effectiveness ratio (ICER) greater than a commonly accepted upper threshold of $200,000 per quality-adjusted life year (QALY) gained. When including all HPV-related outcomes, the ICER for vaccinating up to age 45 years ranged from $315,700 to $440,600 per QALY gained. Assumptions regarding cervical screening compliance, vaccine costs, and the natural history of noncervical HPV-related cancers had major impacts on the cost-effectiveness of the vaccination strategies. Key limitations of the study were related to uncertainties in the data used to inform the models, including the timing of vaccine impact on noncervical cancers and vaccine efficacy at older ages. CONCLUSIONS: Our results from 2 independent models suggest that HPV vaccination for adult women and men aged 30 to 45 years is unlikely to represent good value for money in the US.

Impact of COVID-19-related care disruptions on cervical cancer screening in the United States.

OBJECTIVES: To quantify the secondary impacts of the COVID-19 pandemic disruptions to cervical cancer screening in the United States, stratified by step in the screening process and primary test modality, on cervical cancer burden. METHODS: We conducted a comparative model-based analysis using three independent NCI Cancer Intervention and Surveillance Modeling Network cervical models to quantify the impact of eight alternative COVID-19-related screening disruption scenarios compared to a scenario of no disruptions. Scenarios varied by the duration of the disruption (6 or 24 months), steps in the screening process being disrupted (primary screening, surveillance, colposcopy, excisional treatment), and primary screening modality (cytology alone or cytology plus human papillomavirus "cotesting"). RESULTS: The models consistently showed that COVID-19-related disruptions yield small net increases in cervical cancer cases by 2027, which are greater for women previously screened with cytology compared with cotesting. When disruptions affected all four steps in the screening process under cytology-based screening, there were an additional 5-7 and 38-45 cases per one million screened for 6- and 24-month disruptions, respectively. In contrast, under cotesting, there were additional 4-5 and 35-45 cases per one million screened for 6- and 24-month disruptions, respectively. The majority (58-79%) of the projected increases in cases under cotesting were due to disruptions to surveillance, colposcopies, or excisional treatment, rather than to primary screening. CONCLUSIONS: Women in need of surveillance, colposcopies, or excisional treatment, or whose last primary screen did not involve human papillomavirus testing, may comprise priority groups for reintroductions.

Estimating the health impact of vaccination against ten pathogens in 98 low-income and middle-income countries from 2000 to 2030: a modelling study.

BACKGROUND: The past two decades have seen expansion of childhood vaccination programmes in low-income and middle-income countries (LMICs). We quantify the health impact of these programmes by estimating the deaths and disability-adjusted life-years (DALYs) averted by vaccination against ten pathogens in 98 LMICs between 2000 and 2030. METHODS: 16 independent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, and yellow fever. Using standardised demographic data and vaccine coverage, the impact of vaccination programmes was determined by comparing model estimates from a no-vaccination counterfactual scenario with those from a reported and projected vaccination scenario. We present deaths and DALYs averted between 2000 and 2030 by calendar year and by annual birth cohort. FINDINGS: We estimate that vaccination of the ten selected pathogens will have averted 69 million (95% credible interval 52-88) deaths between 2000 and 2030, of which 37 million (30-48) were averted between 2000 and 2019. From 2000 to 2019, this represents a 45% (36-58) reduction in deaths compared with the counterfactual scenario of no vaccination. Most of this impact is concentrated in a reduction in mortality among children younger than 5 years (57% reduction [52-66]), most notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 120 million (93-150) deaths will be averted by vaccination, of which 58 million (39-76) are due to measles vaccination and 38 million (25-52) are due to hepatitis B vaccination. We estimate that increases in vaccine coverage and introductions of additional vaccines will result in a 72% (59-81) reduction in lifetime mortality in the 2019 birth cohort. INTERPRETATION: Increases in vaccine coverage and the introduction of new vaccines into LMICs have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained. FUNDING: Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.

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

The 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.

Cost-effectiveness of cervical cancer screening with primary HPV testing for unvaccinated women in Sweden.

BACKGROUND: Sweden revised their cervical cancer screening program in 2017 to include cytology-based screening for women aged 23-29 years and primary human papillomavirus (HPV) testing for women aged 30-64 years; however, alternative strategies may be preferred. To inform cervical cancer prevention policies for unvaccinated women, we evaluated the cost-effectiveness of alternative screening strategies, including the current Swedish guidelines. METHODS: We adapted a mathematical simulation model of HPV and cervical cancer to the Swedish context using primary epidemiologic data. We compared the cost-effectiveness of alternative screening strategies that varied by the age to start screening, the age to switch from cytology to HPV testing, HPV strategies not preceded by cytology, screening frequency, and management of HPV-positive/cytology-negative women. RESULTS: We found that the current Swedish guidelines were more costly and less effective than alternative primary HPV-based strategies. All cost-efficient strategies involved primary HPV testing not preceded by cytology for younger women. Given a cost-effectiveness threshold of €85,619 per quality-adjusted life year gained, the optimal strategy involved 5-yearly primary HPV-based screening for women aged 23-50 years and 10-yearly HPV-based screening for women older than age 50 years. CONCLUSIONS: Primary screening based on HPV alone may be considered for unvaccinated women for those countries with similar HPV burdens.