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

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          Abstract

          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.

          Abstract

          Jane Kim and co-workers estimate the potential cost-effectiveness of papillomavirus vaccination for adults aged 30-45 years in the United States.

          Author summary

          Why was this study done?
          • Policies for increasing the upper age limit for human papillomavirus (HPV) vaccination to women and men up to age 45 years are being considered in several countries, but the public health value of such policies is uncertain.

          • An important background consideration is to understand the impact and costs of HPV vaccination in the context of existing cervical cancer screening.

          • This study was conducted to directly inform the deliberations of the Advisory Committee on Immunization Practices (ACIP) to guide HPV vaccination policy for women and men in the United States.

          What did the researchers do and find?
          • Two modeling groups that are part of the Cancer Intervention and Surveillance Modeling Network (CISNET) used independent mathematical models calibrated to the US population to evaluate the cost-effectiveness of extending HPV vaccination in females and males up to ages 30, 35, 40, or 45 years.

          • We conducted the analysis in the context of HPV transmission dynamics, historical HPV vaccination uptake, and detailed cervical cancer screening practice patterns in the US population.

          • We evaluated cost and health outcomes of HPV vaccination up to age 45 years for cervical disease, as well as 6 other disease outcomes (5 noncervical HPV-related cancers and genital warts) in both women and men.

          • Findings from both models suggest that at current prices, HPV vaccination beyond age 26 years is not cost-effective, even under a range of sensitivity analyses and favorable assumptions regarding HPV vaccination effectiveness and costs.

          What do these findings mean?
          • HPV vaccination of women and men aged 30 to 45 years provides limited health benefit at the population level, at a substantial cost (at current HPV vaccine prices).

          • Public health decision-makers considering the option to extend HPV vaccination to adults up to age 45 years should consider this evaluation of the value—and the opportunity costs—of adopting such a policy.

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          Most cited references52

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          Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women

          The Lancet, 374(9686), 301-314
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            • Record: found
            • Abstract: not found
            • Article: not found

            Updating cost-effectiveness--the curious resilience of the $50,000-per-QALY threshold.

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Projections of the cost of cancer care in the United States: 2010-2020.

              Current estimates of the costs of cancer care in the United States are based on data from 2003 and earlier. However, incidence, survival, and practice patterns have been changing for the majority of cancers. Cancer prevalence was estimated and projected by phase of care (initial year following diagnosis, continuing, and last year of life) and tumor site for 13 cancers in men and 16 cancers in women through 2020. Cancer prevalence was calculated from cancer incidence and survival models estimated from Surveillance, Epidemiology, and End Results (SEER) Program data. Annualized net costs were estimated from recent SEER-Medicare linkage data, which included claims through 2006 among beneficiaries aged 65 years and older with a cancer diagnosis. Control subjects without cancer were identified from a 5% random sample of all Medicare beneficiaries residing in the SEER areas to adjust for expenditures not related to cancer. All cost estimates were adjusted to 2010 dollars. Different scenarios for assumptions about future trends in incidence, survival, and cost were assessed with sensitivity analysis. Assuming constant incidence, survival, and cost, we projected 13.8 and 18.1 million cancer survivors in 2010 and 2020, respectively, with associated costs of cancer care of 124.57 and 157.77 billion 2010 US dollars. This 27% increase in medical costs reflects US population changes only. The largest increases were in the continuing phase of care for prostate cancer (42%) and female breast cancer (32%). Projections of current trends in incidence (declining) and survival (increasing) had small effects on 2020 estimates. However, if costs of care increase annually by 2% in the initial and last year of life phases of care, the total cost in 2020 is projected to be $173 billion, which represents a 39% increase from 2010. The national cost of cancer care is substantial and expected to increase because of population changes alone. Our findings have implications for policy makers in planning and allocation of resources.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: Project administrationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Academic Editor
                Journal
                PLoS Med
                PLoS Med
                plos
                plosmed
                PLoS Medicine
                Public Library of Science (San Francisco, CA USA )
                1549-1277
                1549-1676
                11 March 2021
                March 2021
                : 18
                : 3
                : e1003534
                Affiliations
                [1 ] Department of Health Policy and Management, Center for Health Decision Science, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America
                [2 ] Cancer Research Division, Cancer Council New South Wales, Sydney, Australia
                [3 ] School of Public Health, University of Sydney, Sydney, Australia
                [4 ] Department of Health Management and Health Economics, University of Oslo, Oslo, Norway
                UTHealth, UNITED STATES
                Author notes

                I have read the journal’s policy and the authors of this manuscript have the following competing interests: KC is the co-principal investigator of Compass (NCT02328872), an unrelated trial of cervical screening, which is conducted and funded by the VCS Foundation, a government-funded health promotion charity. The VCS Foundation has received equipment and a funding contribution for the Compass trial from Roche Molecular Systems but neither KC nor her institution on her behalf have received funding for this trial or any other project. MAS receives salary support from the National Health & Medical Research Council (Australia) and Cancer Institute NSW. KTS receives salary support from the Cancer Institute NSW. All other authors declare no conflicts.

                Author information
                https://orcid.org/0000-0002-9892-9170
                https://orcid.org/0000-0003-2568-7956
                https://orcid.org/0000-0002-0599-3000
                https://orcid.org/0000-0002-0401-2653
                https://orcid.org/0000-0002-6657-5849
                https://orcid.org/0000-0002-6443-6618
                Article
                PMEDICINE-D-20-00445
                10.1371/journal.pmed.1003534
                7951902
                33705382
                ad1f9d13-1f97-4a3f-b268-94a6b6767c2c
                © 2021 Kim et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 13 February 2020
                : 7 January 2021
                Page count
                Figures: 2, Tables: 4, Pages: 15
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100007316, Division of Cancer Prevention, National Cancer Institute;
                Award ID: U01CA199334
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100007316, Division of Cancer Prevention, National Cancer Institute;
                Award ID: U01CA199334
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100007316, Division of Cancer Prevention, National Cancer Institute;
                Award ID: U01CA199334
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100007316, Division of Cancer Prevention, National Cancer Institute;
                Award ID: U01CA199334
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100007316, Division of Cancer Prevention, National Cancer Institute;
                Award ID: U01CA199334
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100007316, Division of Cancer Prevention, National Cancer Institute;
                Award ID: U01CA199334
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100007316, Division of Cancer Prevention, National Cancer Institute;
                Award ID: U01CA199334
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100007316, Division of Cancer Prevention, National Cancer Institute;
                Award ID: U01CA199334
                Award Recipient :
                JJK, KTS, JK, MAS, EAB, SS, CR, KC received grant support from the U.S. National Cancer Institute at the National Institutes of Health (grant number U01CA199334). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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