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      Assessing cost-effectiveness of HPV vaccines with decision analytic models: what are the distinct challenges of low- and middle-income countries? A protocol for a systematic review

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          Abstract

          Background

          Cervical cancer poses a huge health burden, both to developed and developing nations, making prevention and control strategies necessary. However, the challenges of designing and implementing prevention strategies differ for low- and middle-income countries (LMICs) as compared to countries with fully developed health care systems. Moreover, for many LMICs, much of the data needed for decision analytic modelling, such as prevalence, will most likely only be partly available or measured with much larger uncertainty. Lastly, imperfect implementation of human papillomavirus (HPV) vaccination may influence the effectiveness of cervical cancer prevention in unpredictable ways. This systematic review aims to assess how decision analytic modelling studies of HPV cost-effectiveness in LMICs accounted for the particular challenges faced in such countries. Specifically, the study will assess the following: (1) whether the existing literature on cost-effectiveness modelling of HPV vaccines acknowledges the distinct challenges of LMICs, (2) how these challenges were accommodated in the models, (3) whether certain parameters systemically exhibited large degrees of uncertainty due to lack of data and how influential were these parameters on model-based recommendations, and (4) whether the choice of modelling herd immunity influences model-based recommendations, especially when coverage of a HPV vaccination program is not optimal.

          Methods

          We will conduct a systematic review to identify suitable studies from MEDLINE (via PubMed), EMBASE, NHS Economic Evaluation Database (NHS EED), EconLit, Web of Science, and CEA Registry. Searches will be conducted for studies of interest published since 2006. The searches will be supplemented by hand searching of the most relevant papers found in the search. Studies will be critically appraised using Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement checklist. We will undertake a descriptive, narrative, and interpretative synthesis of data to address the study objectives.

          Discussion

          The proposed systematic review will assess how the cost-effectiveness studies of HPV vaccines accounted for the distinct challenges of LMICs. The gaps identified will expose areas for additional research as well as challenges that need to be accounted for in future modelling studies.

          Systematic review registration

          PROSPERO CRD42015017870.

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          Most cited references12

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          The causal relation between human papillomavirus and cervical cancer.

          The causal role of human papillomavirus infections in cervical cancer has been documented beyond reasonable doubt. The association is present in virtually all cervical cancer cases worldwide. It is the right time for medical societies and public health regulators to consider this evidence and to define its preventive and clinical implications. A comprehensive review of key studies and results is presented.
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            HPV screening for cervical cancer in rural India.

            In October 1999, we began to measure the effect of a single round of screening by testing for human papillomavirus (HPV), cytologic testing, or visual inspection of the cervix with acetic acid (VIA) on the incidence of cervical cancer and the associated rates of death in the Osmanabad district in India. In this cluster-randomized trial, 52 clusters of villages, with a total of 131,746 healthy women between the ages of 30 and 59 years, were randomly assigned to four groups of 13 clusters each. The groups were randomly assigned to undergo screening by HPV testing (34,126 women), cytologic testing (32,058), or VIA (34,074) or to receive standard care (31,488, control group). Women who had positive results on screening underwent colposcopy and directed biopsies, and those with cervical precancerous lesions or cancer received appropriate treatment. In the HPV-testing group, cervical cancer was diagnosed in 127 subjects (of whom 39 had stage II or higher), as compared with 118 subjects (of whom 82 had advanced disease) in the control group (hazard ratio for the detection of advanced cancer in the HPV-testing group, 0.47; 95% confidence interval [CI], 0.32 to 0.69). There were 34 deaths from cancer in the HPV-testing group, as compared with 64 in the control group (hazard ratio, 0.52; 95% CI, 0.33 to 0.83). No significant reductions in the numbers of advanced cancers or deaths were observed in the cytologic-testing group or in the VIA group, as compared with the control group. Mild adverse events were reported in 0.1% of screened women. In a low-resource setting, a single round of HPV testing was associated with a significant reduction in the numbers of advanced cervical cancers and deaths from cervical cancer. 2009 Massachusetts Medical Society
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              Epidemiology and natural history of human papillomavirus infections and type-specific implications in cervical neoplasia.

              Worldwide human papillomavirus (HPV) prevalence in women with normal cytology at any given point in time is approximately 10% indicating that HPV is one of the most common sexually transmitted infections. HPV-16 is consistently the most common type and HPV-18 the second with some minor regional differences. Furthermore, across the spectrum of cervical lesions, HPV-16 is consistently the most common HPV type contributing to 50-55% of invasive cervical cancer cases strongly suggesting that this viral type has a biological advantage for transmission, persistency and transformation. The same phenomenon is observed albeit at a lower level for HPV-18 and HPV-45. Sexual behavioral patterns across age groups and populations are central to the description of the HPV circulation and of the risk of infection. The concept of group sexual behavior (in addition to individual sexual behavior) is important in exploring HPV transmission and has implications for defining and monitoring HPV and cancer prevention strategies. In natural history studies, the pattern of HPV DNA prevalence by age groups is similar to the patterns of HPV incidence. Rates of exposure in young women are high and often include multiple types. There is a spontaneous and rapid decrease of the HPV DNA detection rates in the middle-age groups followed by a second rise in the post-menopausal years. This article reviews: 1) the evidence in relation to the burden of HPV infections in the world and the contributions of each HPV type to the spectrum of cervical cellular changes spanning from normal cytology to invasive cervical cancer; 2) the critical role of the patterns of sexual behavior in the populations; and 3) selected aspects of the technical and methodological complexity of natural history studies of HPV and cervical neoplasia.
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                Author and article information

                Contributors
                ekwunife@uni-bremen.de
                andreas.gerber@iqwig.de
                Christoph.Mosch@uni-wh.de
                jfomahon@tcd.ie
                Stefan.Lhachimi@uni-bremen.de
                Journal
                Syst Rev
                Syst Rev
                Systematic Reviews
                BioMed Central (London )
                2046-4053
                12 May 2015
                12 May 2015
                2015
                : 4
                : 68
                Affiliations
                [ ]Cooperative Research Group for Evidence-Based Public Health, Department of Prevention and Evaluation, Leibniz Institute for Prevention Research and Epidemiology—BIPS, Bremen, Germany
                [ ]Department of Clinical Pharmacy and Pharmacy Management, Nnamdi Azikiwe University, Awka, Nigeria
                [ ]Institute for Quality and Efficiency in Health Care (IQWiG), Cologne, Germany
                [ ]Institute for Research in Operative Medicine (IFOM), Universität Witten/Herdecke, Witten, Germany
                [ ]Department of Health Policy and Management, School of Medicine, Trinity College Dublin, Dublin, Ireland
                [ ]Institute for Public Health and Nursing Research—IPP, Health Sciences Bremen, University of Bremen, Bremen, Germany
                Article
                57
                10.1186/s13643-015-0057-8
                4489355
                25963745
                46ef8592-4b94-45f1-878d-3417a40e940f
                © Ekwunife et al.; licensee BioMed Central. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 31 March 2015
                : 5 May 2015
                Categories
                Protocol
                Custom metadata
                © The Author(s) 2015

                Public health
                uterine cervical neoplasm,papillomavirus vaccines,mass vaccination,cost-effectiveness analysis,low- and middle-income countries

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