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Scale-up of radiotherapy for cervical cancer in the era of human papillomavirus vaccination in low-income and middle-income countries: a model-based analysis of need and economic impact.

ABSTRACT: BACKGROUND:Radiotherapy is standard of care for cervical cancer, but major global gaps in access exist, particularly in low-income and middle-income countries. We modelled the health and economic benefits of a 20-year radiotherapy scale-up to estimate the long-term demand for treatment in the context of human papillomavirus (HPV) vaccination. METHODS:We applied the Global Task Force on Radiotherapy for Cancer Control investment framework to model the health and economic benefits of scaling up external-beam radiotherapy and brachytherapy for cervical cancer in upper-middle-income, lower-middle-income, and low-income countries between 2015 and 2035. We estimated the unique costs of external-beam radiotherapy and brachytherapy and included a specific valuation of women's caregiving contributions. Model outcomes life-years gained and the human capital and full income net present value of investment. We estimated the effects of stage at diagnosis, radiotherapy delivery system, and simultaneous HPV vaccination (75% coverage) up to a time horizon set at 2072. FINDINGS:For the period from 2015 to 2035, we estimated that 9·4 million women in low-income and middle-income countries required treatment with external-beam radiotherapy, of which 7·0 million also required treatment with brachytherapy. Incremental scale-up of radiotherapy in these countries from 2015 to meet optimal radiotherapy demand by 2035 yielded 11·4 million life-years gained, $59·3 billion in human capital net present value (-$1·5 billion in low-income, $19·9 billion in lower-middle-income, and $40·9 billion in upper-middle-income countries), and $151·5 billion in full income net present value ($1·5 billion in low-income countries, $53·6 billion in lower-middle-income countries, and $96·4 billion in upper-middle-income countries). Benefits increased with advanced stage of cervical cancer and more efficient scale up of radiotherapy. Bivalent HPV vaccination of 12-year-old girls resulted in a 3·9% reduction in incident cases from 2015-2035. By 2072, when the first vaccinated cohort of girls reaches 70 years of age, vaccination yielded a 22·9% reduction in cervical cancer incidence, with 38·4 million requiring external-beam radiotherapy and 28·8 million requiring brachytherapy. INTERPRETATION:Effective cervical cancer control requires a comprehensive strategy. Even with HPV vaccination, radiotherapy treatment scale-up remains essential and produces large health benefits and a strong return on investment to countries at different levels of development. FUNDING:None.

SUBMITTER: Rodin D

PROVIDER: S-EPMC7055962 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Scale-up of radiotherapy for cervical cancer in the era of human papillomavirus vaccination in low-income and middle-income countries: a model-based analysis of need and economic impact.

Rodin Danielle D Burger Emily A EA Atun Rifat R Barton Michael M Gospodarowicz Mary M Grover Surbhi S Hanna Timothy P TP Jaffray David A DA Knaul Felicia M FM Lievens Yolande Y Zubizarreta Eduardo E Milosevic Michael M

The Lancet. Oncology 20190528 7

<h4>Background</h4>Radiotherapy is standard of care for cervical cancer, but major global gaps in access exist, particularly in low-income and middle-income countries. We modelled the health and economic benefits of a 20-year radiotherapy scale-up to estimate the long-term demand for treatment in the context of human papillomavirus (HPV) vaccination.<h4>Methods</h4>We applied the Global Task Force on Radiotherapy for Cancer Control investment framework to model the health and economic benefits o ...[more]

PMID: 31151906

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Project description:BackgroundIntroduction of human papillomavirus (HPV) vaccination has been slow in low-income and middle-income countries (LMICs) because of resource constraints and worldwide shortage of vaccine supplies. To help inform WHO recommendations, we modelled various HPV vaccination strategies to examine the optimal use of limited vaccine supplies and best allocation of scarce resources in LMICs in the context of the WHO global call to eliminate cervical cancer as a public health problem.MethodsIn this mathematical modelling analysis, we developed HPV-ADVISE LMIC, a transmission-dynamic model of HPV infection and diseases calibrated to four LMICs: India, Vietnam, Uganda, and Nigeria. For different vaccination strategies that encompassed use of a nine-valent vaccine (or a two-valent or four-valent vaccine assuming high cross-protection), we estimated three outcomes: reduction in the age-standardised rate of cervical cancer, number of doses needed to prevent one case of cervical cancer (NNV; as a measure of efficiency), and the incremental cost-effectiveness ratio (ICER; in 2017 international $ per disability-adjusted life-year [DALY] averted). We examined different vaccination strategies by varying the ages of routine HPV vaccination and number of age cohorts vaccinated, the population targeted, and the number of doses used. In our base case, we assumed 100% lifetime protection against HPV-16, HPV-18, HPV-31, HPV-33, HPV-45, HPV-52, and HPV-58; vaccination coverage of 80%; and a time horizon of 100 years. For the cost-effectiveness analysis, we used a 3% discount rate. Elimination of cervical cancer was defined as an age-standardised incidence of less than four cases per 100 000 woman-years.FindingsWe predicted that HPV vaccination could lead to cervical cancer elimination in Vietnam, India, and Nigeria, but not in Uganda. Compared with no vaccination, strategies that involved vaccinating girls aged 9-14 years with two doses were predicted to be the most efficient and cost-effective in all four LMICs. NNV ranged from 78 to 381 and ICER ranged from $28 per DALY averted to $1406 per DALY averted depending on the country. The most efficient and cost-effective strategies were routine vaccination of girls aged 14 years, with or without a later switch to routine vaccination of girls aged 9 years, and routine vaccination of girls aged 9 years with a 5-year extended interval between doses and a catch-up programme at age 14 years. Vaccinating boys (aged 9-14 years) or women aged 18 years or older resulted in substantially higher NNVs and ICERs.InterpretationWe identified two strategies that could maximise efforts to prevent cervical cancer in LMICs given constraints on vaccine supplies and costs and that would allow a maximum of LMICs to introduce HPV vaccination.FundingWorld Health Organization, Canadian Institute of Health Research, Fonds de recherche du Québec-Santé, Compute Canada, PATH, and The Bill & Melinda Gates Foundation.TranslationsFor the French and Spanish translations of the abstract see Supplementary Materials section.

Project description:BackgroundMost health economic evaluations of childhood vaccination only capture the health and short-term economic benefits. Measuring broader, long-term effects of vaccination on productivity and externalities could provide a more complete picture of the value of vaccines.MethodMEDLINE, EconLit and NHS-EED databases were searched for articles published between January 1990 and July 2011, which captured broader economic benefits of vaccines in low and middle income countries. Studies were included if they captured at least one of the following categories on broader economic impact: outcome-related productivity gains, behaviour-related productivity gains, ecological externalities, equity gains, financial sustainability gains or macroeconomic benefits.ResultsTwenty-six relevant studies were found, including observational studies, economic models and contingent valuation studies. Of the identified broader impacts, outcome-related productivity gains and ecological externalities were most commonly accounted for. No studies captured behaviour-related productivity gains or macroeconomic effects. There was some evidence to show that vaccinated children 8-14 years of age benefit from increased cognitive ability. Productivity loss due to morbidity and mortality was generally measured using the human capital approach. When included, herd immunity effects were functions of coverage rates or based on reduction in disease outcomes. External effects of vaccines were observed in terms of equitable health outcomes and contribution towards synergistic and financially sustainable healthcare programs.ConclusionDespite substantial variation in the methods of measurement and outcomes used, the inclusion of broader economic impact was found to improve the attractiveness of vaccination. Further research is needed on how different tools and techniques can be used in combination to capture the broader impact of vaccination in a way that is consistent with other health economic evaluations. In addition, more country level evidence is needed from low and middle income countries to justify future investments in vaccines and immunization programs. Finally, the proposed broader economic impact framework may contribute towards better communication of the economic arguments surrounding vaccine uptake, leading to investments in immunization by stakeholders outside of the traditional health care sector such as ministries of finance and national treasuries.

Project description:BackgroundThe WHO Director-General has issued a call for action to eliminate cervical cancer as a public health problem. To help inform global efforts, we modelled potential human papillomavirus (HPV) vaccination and cervical screening scenarios in low-income and lower-middle-income countries (LMICs) to examine the feasibility and timing of elimination at different thresholds, and to estimate the number of cervical cancer cases averted on the path to elimination.MethodsThe WHO Cervical Cancer Elimination Modelling Consortium (CCEMC), which consists of three independent transmission-dynamic models identified by WHO according to predefined criteria, projected reductions in cervical cancer incidence over time in 78 LMICs for three standardised base-case scenarios: girls-only vaccination; girls-only vaccination and once-lifetime screening; and girls-only vaccination and twice-lifetime screening. Girls were vaccinated at age 9 years (with a catch-up to age 14 years), assuming 90% coverage and 100% lifetime protection against HPV types 16, 18, 31, 33, 45, 52, and 58. Cervical screening involved HPV testing once or twice per lifetime at ages 35 years and 45 years, with uptake increasing from 45% (2023) to 90% (2045 onwards). The elimination thresholds examined were an average age-standardised cervical cancer incidence of four or fewer cases per 100 000 women-years and ten or fewer cases per 100 000 women-years, and an 85% or greater reduction in incidence. Sensitivity analyses were done, varying vaccination and screening strategies and assumptions. We summarised results using the median (range) of model predictions.FindingsGirls-only HPV vaccination was predicted to reduce the median age-standardised cervical cancer incidence in LMICs from 19·8 (range 19·4-19·8) to 2·1 (2·0-2·6) cases per 100 000 women-years over the next century (89·4% [86·2-90·1] reduction), and to avert 61·0 million (60·5-63·0) cases during this period. Adding twice-lifetime screening reduced the incidence to 0·7 (0·6-1·6) cases per 100 000 women-years (96·7% [91·3-96·7] reduction) and averted an extra 12·1 million (9·5-13·7) cases. Girls-only vaccination was predicted to result in elimination in 60% (58-65) of LMICs based on the threshold of four or fewer cases per 100 000 women-years, in 99% (89-100) of LMICs based on the threshold of ten or fewer cases per 100 000 women-years, and in 87% (37-99) of LMICs based on the 85% or greater reduction threshold. When adding twice-lifetime screening, 100% (71-100) of LMICs reached elimination for all three thresholds. In regions in which all countries can achieve cervical cancer elimination with girls-only vaccination, elimination could occur between 2059 and 2102, depending on the threshold and region. Introducing twice-lifetime screening accelerated elimination by 11-31 years. Long-term vaccine protection was required for elimination.InterpretationPredictions were consistent across our three models and suggest that high HPV vaccination coverage of girls can lead to cervical cancer elimination in most LMICs by the end of the century. Screening with high uptake will expedite reductions and will be necessary to eliminate cervical cancer in countries with the highest burden.FundingWHO, UNDP, UN Population Fund, UNICEF-WHO-World Bank Special Program of Research, Development and Research Training in Human Reproduction, Canadian Institute of Health Research, Fonds de recherche du Québec-Santé, Compute Canada, National Health and Medical Research Council Australia Centre for Research Excellence in Cervical Cancer Control.

Project description:BackgroundThis systematic review aimed to describe common aetiologies of severe and non-severe community acquired pneumonia among children aged 1 month to 9 years in low- and middle-income countries.MethodsWe searched the MEDLINE, EMBASE, and PubMed online databases for studies published from January 2010 to August 30, 2020. We included studies on acute community-acquired pneumonia or acute lower respiratory tract infection with ≥1 year of continuous data collection; clear consistent case definition for pneumonia; >1 specimen type (except empyema studies where only pleural fluid was required); testing for >1 pathogen including both viruses and bacteria. Two researchers reviewed the studies independently. Results were presented as a narrative summary. Quality of evidence was assessed with the Quality Assessment Tool for Quantitative Studies. The study was registered on PROSPERO [CRD42020206830].ResultsWe screened 5184 records; 1305 duplicates were removed. The remaining 3879 titles and abstracts were screened. Of these, 557 articles were identified for full-text review, and 55 met the inclusion criteria - 10 case-control studies, three post-mortem studies, 11 surveillance studies, eight cohort studies, five cross-sectional studies, 12 studies with another design and six studies that included patients with pleural effusions or empyema. Studies which described disease by severity showed higher bacterial detection (Streptococcus pneumoniae, Staphylococcus aureus) in severe vs non-severe cases. The most common virus causing severe disease was respiratory syncytial virus (RSV). Pathogens varied by age, with RSV and adenovirus more common in younger children. Influenza and atypical bacteria were more common in children 5-14 years than younger children. Malnourished and HIV-infected children had higher rates of pneumonia due to bacteria or tuberculosis.ConclusionsSeveral viral and bacterial pathogens were identified as important targets for prevention and treatment. Bacterial pathogens remain an important cause of moderate to severe disease, particularly in children with comorbidities despite widespread PCV and Hib vaccination.

Dataset Information

Scale-up of radiotherapy for cervical cancer in the era of human papillomavirus vaccination in low-income and middle-income countries: a model-based analysis of need and economic impact.

Publications

Scale-up of radiotherapy for cervical cancer in the era of human papillomavirus vaccination in low-income and middle-income countries: a model-based analysis of need and economic impact.

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