Mortality impact of achieving WHO cervical cancer elimination targets: a comparative modelling analysis in 78 low-income and lower-middle-income countries.
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SUBMITTER: Canfell K
PROVIDER: S-EPMC7043006 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
| S-EPMC7043009 | biostudies-literature
Project description:Cervical cancer is a malignant tumour that occurs in the cervix and is classified into two histological types, adenocarcinoma and squamous cell carcinoma (SCC); SCC is more common and accounts for 70% of all cases. In 2018 there were ~569,000 new cases of cervical cancer diagnosed worldwide and ~311,000 deaths were attributed to cervical cancer. Of these, between 84 and 90% occurred in low- and middle-income countries (LMICs) such as South Africa, India, China and Brazil. The most common cause of cervical cancer is persistent infection caused by the sexually transmitted human papilloma virus. Other factors that contribute to the incidence of cervical cancer include geography, traditional practices and beliefs, the screening levels, socioeconomic status, healthcare access, public awareness, use of oral contraceptives, smoking and co-infection with HIV. An estimated 11 million women from LMICs will be diagnosed with cervical cancer in the next 10-20 years. The aim of this review was to explore various types of genetic and epigenetic factors that influence the development, progression or suppression of cervical cancer.
| S-EPMC7400218 | biostudies-literature
Project description:ImportanceMany randomized clinical trials (RCTs) led by high-income countries (HICs) now enroll patients from lower middle-income countries (LMICs) and upper middle-income countries (UMICs). Although enrolling diverse populations promotes research collaborations, there are issues regarding which countries participate in RCTs and how this participation may contribute to global research.ObjectiveTo describe which UMICs and LMICs participate in RCTs led by HICs.Design, setting, and participantsA cross-sectional study of all oncology RCTs published globally during January 1, 2014, to December 31, 2017, was conducted. The study cohort was restricted to RCTs led by HICs that enrolled participants from LMICs and UMICs. Study analyses were conducted in November 1, 2021, to May 31, 2022.Main outcomes and measuresA bibliometric approach (Web of Science 2007-2017) was used to explore whether RCT participation was proportional to other measures of cancer research activity. Participation in RCTs (ie, percentage of RCTs in the cohort in which each LMIC and UMIC participated) was compared with country-level cancer research bibliometric output (ie, percentage of total cancer research bibliometric output from the same group of countries that came from a specific LMIC and UMIC).ResultsAmong the 636 HIC-led RCTs, 186 trials (29%) enrolled patients in LMICs (n = 84 trials involving 11 LMICs) and/or UMICs (n = 181 trials involving 26 UMICs). The most common participating LMICs were India (42 [50%]), Ukraine (39 [46%]), Philippines (23 [27%]), and Egypt (12 [14%]). The most common participating UMICs were Russia (115 [64%]), Brazil (94 [52%]), Romania (62 [34%]), China (56 [31%]), Mexico (56 [31%]), and South Africa (54 [30%]). Several LMICs are overrepresented in the cohort of RCTs based on proportional cancer research bibliometric output: Ukraine (46% of RCTs but 2% of cancer research bibliometric output), Philippines (27% RCTs, 1% output), and Georgia (8% RCTs, 0.2% output). Overrepresented UMICs include Russia (64% RCTs, 2% output), Romania (34% RCTs, 2% output), Mexico (31% RCTs, 2% output), and South Africa (30% RCTs, 1% output).Conclusions and relevanceIn this cross-sectional study, a substantial proportion of RCTs led by HICs enrolled patients in LMICs and UMICs. The LMICs and UMICs that participated in these trials did not match overall cancer bibliometric output as a surrogate for research ecosystem maturity. Reasons for this apparent discordance and how these data may inform future capacity-strengthening activities require further study.
| S-EPMC9389348 | biostudies-literature
Project description:Chronic diseases are increasingly becoming a health burden in lower- and middle-income countries, putting pressure on public health efforts to scale up interventions. This article reviews current efforts in interventions on a population and individual level. Population-level interventions include ongoing efforts to reduce smoking rates, reduce intake of salt and trans-fatty acids, and increase physical activity in increasingly sedentary populations. Individual-level interventions include control and treatment of risk factors for chronic diseases and secondary prevention. This review also discusses the barriers in interventions, particularly those specific to low- and middle-income countries. Continued discussion of proven cost-effective interventions for chronic diseases in the developing world will be useful for improving public health policy.
| S-EPMC3686269 | biostudies-other
Project description:Cervical cancer is the fourth leading cause of cancer death in women, with 85% of cases and deaths occurring in developing countries. While organized screening programs have reduced cervical cancer incidence in high-income countries through detection and treatment of precancerous lesions, the implementation of organized screening has not been effective in low-resource settings due to lack of infrastructure and limited budgets. Our objective was to estimate the cost of comprehensive primary and secondary cervical cancer prevention in low- and middle-income countries.We performed a modeling analysis to estimate 1) for girls aged 10 years, the cost of 2-dose human papillomavirus (HPV) vaccination; and 2) for women aged 30 to 49 years, the cost of cervical cancer screening (with visual inspection with acetic acid (VIA), HPV testing, or cytology) and preventive treatment in 102 low- and middle-income countries from 2015 to 2024. We used an Excel-based costing and service utilization model to estimate financial costs (2013 US$) based on prevalence of HPV, prevalence of precancerous lesions, and screening test performance. Where epidemiologic data were unavailable, we extrapolated from settings with data using an individual-based microsimulation model of cervical carcinogenesis (calibrated to 20 settings) and multivariate regression. Total HPV vaccination costs ranged from US$8.6 billion to US$24.2 billion for all scenarios considered (immediate, 5-year, or 10-year roll-out; price per dose US$4.55-US$70 by country income level). The total cost of screening and preventive treatment ranged from US$5.1 billion (10-year roll-out, screening once at age 35 years) to US$42.3 billion (immediate roll-out, high intensity screening). Limitations of this analysis include the assumption of standardized protocols by country income level that did not account for the potential presence of multiple screening modalities or management strategies within a country, and extrapolation of cost and epidemiologic data to settings where data were limited.The estimated cost of comprehensive cervical cancer prevention with 2-dose HPV vaccination of 10-year-old girls and screening of women aged 30 to 49 years ranges from US$13.7 billion to US$66.5 billion, depending on speed of roll-out, vaccine price per dose, and screening test and frequency. Findings demonstrate the substantial impact of vaccine price in middle-income countries that are not eligible for assistance from Gavi, the Vaccine Alliance. Replacing routine cytology with HPV-based screening may reduce total costs. Data on the health impact and relative cost-effectiveness of strategies are needed to determine the best value for public health dollars.
| S-EPMC5053484 | biostudies-other
Project description:Cervical cancer is the fourth leading cause of cancer-related death in women worldwide, with 90% of cases occurring in low- and middle-income countries (LMICs). There has been a global effort to increase access to affordable screening in these settings; however, a corresponding increase in availability of effective and inexpensive treatment modalities for ablating or excising precancerous lesions is also needed to decrease mortality. This article reviews the current landscape of available and developing technologies for treatment of cervical precancer in LMICs. At present, the standard treatment of most precancerous lesions in LMICs is gas-based cryotherapy. This low-cost, effective technology is an expedient treatment in many areas; however, obtaining and transporting gas is often difficult, and unwieldy gas tanks are not conducive to mobile health campaigns. There are several promising ablative technologies in development that are gasless or require less gas than conventional cryotherapy. Although further evaluation of the efficacy and cost-effectiveness is needed, several of these technologies are safe and can now be implemented in LMICs. Nonsurgical therapies, such as therapeutic vaccines, antivirals, and topical applications, are also promising, but most remain in early-stage trials. The establishment of evidence-based standardized protocols for available treatments and the development and introduction of novel technologies are necessary steps in overcoming barriers to treatment in LMICs and decreasing the global burden of cervical cancer. Guidance from WHO on emerging treatment technologies is also needed.
| S-EPMC5560450 | biostudies-other
Project description:BackgroundEnterotoxigenic Escherichia coli (ETEC) and shigella are two major pathogens that cause moderate-to-severe diarrhoea in children younger than 5 years. Diarrhoea is associated with an increased risk of stunting, which puts children at risk of death due to other infectious diseases.MethodsWe modelled ETEC-related and shigella-related mortality and the effect of moderate-to-severe diarrhoea episodes to determine the number of children with stunting due to these infections in 79 low-income and lower middle-income countries. We applied population attributable risk for increased number of deaths due to other infectious diseases in children who are stunted. We calculated 95% uncertainty intervals (UIs) for the point estimates.FindingsIn children younger than 5 years, we estimate 196 million (95% UI 135-269) episodes of ETEC and shigella diarrhoea occur annually, resulting in 3·5 million (0·8-5·4) cases of moderate-to-severe stunting and 44 400 (29 400-59 800) total ETEC deaths and 63 100 (44 000-81 900) total shigella deaths in 2015. Additional infectious disease mortality due to stunting resulted in increases of 24% (8-34; for ETEC) and 28% (10-39; for shigella) over direct deaths due to diarrhoeal episodes. The distribution of mortality and morbidity varied geographically, with African Region and Eastern Mediterranean Region countries bearing the greatest burden.InterpretationThe expanded effects of non-fatal ETEC and shigella-related diarrhoeal episodes can have lasting consequences. Prevention of these infections could reduce the risk of direct death and stunting and deaths due to other infectious diseases. Understanding the countries and populations with the highest disease risk helps to target interventions for the most vulnerable populations.FundingThe Bill & Melinda Gates Foundation.
| S-EPMC6379821 | biostudies-literature
Project description: Not available
| S-EPMC6422246 | biostudies-literature
Project description:The World Health Organization announced an ambitious call for cervical cancer elimination worldwide. With existing prevention and treatment modalities, cervical cancer elimination is now within reach for high-income countries. Despite limited financing and capacity constraints in low-and-middle-income countries (LMICs), prevention and control efforts can be supported through integrated services and new technologies. We conducted this scoping review to outline a roadmap toward cervical cancer elimination in LMICs and highlight evidence-based interventions and research priorities to accelerate cervical cancer elimination. We reviewed and synthesized literature from 2010 to 2020 on primary and secondary cervical cancer prevention strategies. In addition, we conducted expert interviews with gynecologic and infectious disease providers, researchers, and LMIC health officials. Using these data, we developed a logic model to summarize the current state of science and identified evidence gaps and priority research questions for each prevention strategy. The logic model for cervical cancer elimination maps the needs for improved collaboration between policy makers, production and supply, healthcare systems, providers, health workers, and communities. The model articulates responsibilities for stakeholders and visualizes processes to increase access to and coverage of prevention methods. We discuss the challenges of contextual factors and highlight innovation needs. Effective prevention methods include HPV vaccination, screening using visual inspection and HPV testing, and thermocoagulation. However, vaccine coverage remains low in LMICs. New strategies, including single-dose vaccination could enhance impact. Loss to follow-up and treatment delays could be addressed by improved same-day screen-and-treat technologies. We provide a practical framework to guide cervical cancer elimination in LMICs. The scoping review highlights existing and innovative strategies, unmet needs, and collaborations required to achieve elimination across implementation contexts.
| S-EPMC8281011 | biostudies-literature
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.
| S-EPMC8554391 | biostudies-literature