Research
Etiology and primary prevention of carcinogenic infections
- Infection-attributable cancer burden: global and local
IARC is the global reference for estimates of the infection-attributable cancer burden (https://gco.iarc.fr/causes/infections). These estimates require constant updating and improvement with pertinent exposure assessment tools and the latest global cancer incidence data. Current research priorities include estimates of the cancer burden due to HIV (e.g. cervical cancer, Kaposi sarcoma, anal cancer), Epstein–Barr virus (e.g. non-Hodgkin lymphoma, gastric carcinoma), and hepatitis viruses (see below). Given that infections are amenable to prevention, such estimates are key indicators for cancer control.
- Public health decision modelling: global and local
EPR has developed expertise in quantitative modelling of HPV transmission, HPV vaccination, and cervical cancer screening. A range of open-source models are used to project the expected impact of cervical cancer control measures and to study phenomena that cannot be investigated exclusively on the basis of empirical data. These models are informed by EPR’s studies of the impacts of HPV vaccination (see below). The goal of this project is to support the design, implementation, and evaluation of HPV-related cancer control programmes in LMICs.
- Impacts of HPV vaccination programmes in LMICs
The evaluation of the effectiveness of HPV vaccination in LMIC settings is crucial, to understand the best implementation strategies, inform cancer control programmes, and sustain stakeholders’ long-term commitment to HPV vaccination. EPR is coordinating a multicentre series of studies based on repeated surveys of HPV prevalence, before and after vaccination. Current sites of collaboration include Bhutan, Rwanda, Armenia, and Uganda. The protocol is also being expanded to other LMICs that represent different implementation scenarios.
- HPV vaccine trials in India
EPR is coordinating a multicentre study of 17 000 females vaccinated at age 10–18 years with one, two, or three doses of quadrivalent HPV vaccine. Long-term follow-up shows that a single dose is as protective as two or three doses against persistent HPV16/18 infections (https://clinicaltrials.gov/ct2/show/NCT00923702). Study outcomes are regularly shared with the WHO Strategic Advisory Group of Experts on Immunization. EPR is also providing technical support to a phase II/III study comparing the safety and immunogenicity of the Serum Institute of India (SIIL) quadrivalent HPV vaccine versus Gardasil in males and females aged 9–14 years (two-dose cohort) and 15–26 years (three-dose cohort).
Visit webpage - PAPRICA (Intervention to improve HPV vaccine coverage in France)
The PAPRICA study is an educational intervention based on a behavioural change model among general practitioners in Lyon, France, aiming to increase knowledge and positive attitudes towards HPV vaccination (https://clinicaltrials.gov/ct2/show/NCT03592225).
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- HPV-AHEAD/HEADLAcE (Role of HPV in causality and prognosis of head and neck cancer)
In the HPV-AHEAD study, the HPV-attributable fraction is being assessed in 8000 head and neck cancers from India and Europe (Belgium, France, Germany, Greece, Italy, and Spain). The stringent protocol includes the detection of both viral DNA and RNA, as well as p16INK4a staining (https://hpv-ahead.iarc.fr/). The HEADLAcE study, with partners from Latin America (Brazil, Colombia, and Peru), and Europe (France, Italy, and Spain), has a similar protocol to assess HPV etiology, and also has a prospective phase in Brazil and Italy to evaluate how HPV biomarkers predict tumour recurrence and survival.
- H. pylori testing and treatment to prevent gastric cancer
EPR is involved in studies of H. pylori eradication to prevent gastric cancer, most notably the HELPER trial, nested within the National Cancer Screening Program of the Republic of Korea. HELPER has recruited more than 12 000 people aged 40–65 years, and 5268 H. pylori-positive participants were randomized to eradication therapy or placebo. The GISTAR study aims to determine whether H. pylori eradication combined with endoscopic screening of atrophic gastritis reduces mortality from gastric cancer among people aged 40–64 years (https://www.gistar.eu).
- Elimination of viral hepatitis
EPR has a programme to estimate and monitor changes in the global burden of hepatocellular carcinoma, as well as its precursor cirrhosis, attributable to HBV and HCV infection. In collaboration with the Department of HIV/AIDS and the Global Hepatitis Programme of WHO, EPR is using a combination of literature reviews and implementation of standard protocols in sentinel centres (e.g. hepatology or gastroenterology units) to develop the best estimates of the national HBV- and HCV-related burden of cirrhosis and hepatocellular carcinoma, thereby measuring local and global progress towards the WHO target for elimination of viral hepatitis.
Screening of asymptomatic at-risk populations
- Cancer Screening in Five Continents (CanScreen5)
The CanScreen5 project aims to uniformly collect, analyse, and disseminate data on the characteristics and performance of cancer screening programmes globally. A web-based open access platform facilitates data interpretation (https://canscreen5.iarc.fr), and self-paced training modules enable participants to propose measures to improve the quality of cancer screening programmes, to maximize the benefits and minimize the potential harms (https://learning.iarc.fr/edp/resources/pgm-cancer-screening). Capacity-building is supported through regional training sessions with programme managers, in partnership with WHO regional offices.
CANSCREEN5 WEBSITE TOUR WATCH VIDEO
- RISCC (Risk-Based Screening for Cervical Cancer for Europe)
RISCC is a European Union-funded consortium aiming to identify optimal risk-based cervical cancer screening protocols. The RISCC consortium is based on data from four large European population-based randomized controlled trials of HPV screening and from the Finnish phase IV cluster-randomized vaccination trial of vaccinating only girls versus both girls and boys. EPR contributes to RISCC through its open-source model for disease progression by assessing health gains and screening-related harms associated with different risk-based programmes (https://www.riscc-h2020.eu/).
- CBIG-SCREEN (Cervical cancer screening in vulnerable women in Europe)
EPR is supporting the implementation of this multicentre research study, which aims to tackle inequality in the cervical cancer screening continuum in Estonia, Portugal, and Romania. These focus countries have been identified to represent different health-care settings within Europe. The interventions aim to increase screening participation among vulnerable women from the current 26% to 45%, and intend to offer support to policy-makers and national programmes to help Europe reach the WHO 2030 target of screening at least 70% of women for cervical cancer.
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- ESTAMPA (HPV-based cervical screening and triage methods in Latin America)
ESTAMPA is a multicentre study aiming to evaluate different techniques and strategies to triage HPV-positive women in Latin America (visual inspection, Pap test, liquid-based cytology, dual-stain cytology, HPV genotyping, HPV persistence, novel tests for E6/E7 oncoproteins and methylation, short-term repeat HPV testing, risk stratification models). The study includes a 5-year screening round, at which programmatic aspects and implementation research questions to guide scale-up of HPV-based screening in LMIC contexts will be evaluated.
- CESTA (HPV-based cervical screen-and-treat approaches for high-risk populations)
The multicentre CESTA (Cervical cancer screening and treatment algorithms using HPV testing in Africa) study aims to provide clear evidence on the efficacy of two HPV screen-and-treat algorithms with or without visual triage recommended by the WHO guidelines. CESTA targets underscreened and HIV-positive women living in Senegal and South Africa. The acceptability and side-effects of ablative treatment are also being investigated, as well as the use of other novel triage tests within HPV screen-and-treat scenarios.
- AIMA-CC (Cervical cancer screening of HIV-positive women in LMICs)
AIMA-CC aims to provide evidence on the effectiveness and feasibility of HPV-based screening algorithms (self-sampling, Xpert HPV assay) among HIV-positive women in low-resource settings. This cross-sectional study is under way in Abidjan (Côte d’Ivoire), Bobo-Dioulasso (Burkina Faso), and Phnom Penh (Cambodia) and involves about 2000 women receiving highly active antiretroviral therapy. AIMA-CC (“Follow-up”) will also assess the effectiveness of thermal ablation for the treatment of cervical precancerous lesions (https://clinicaltrials.gov/ct2/show/NCT03789513).
- SAVE-CERVIX (Artificial intelligence image recognition in cervical screening in LMICs)
EPR is supporting the development and evaluation of promising new cervical imaging technologies for LMICs. This includes a device (n-AVE) that uses high-quality images and artificial intelligence (AI) to give a colposcopic diagnosis. Training the AI-based classifier on more images obtained in colposcopy clinics in India and Thailand is under way, to improve its accuracy and generalizability to different settings and locations (https://www.isrctn.com/ISRCTN18333554). EPR is also developing an application of a new AI-based algorithm to detect HPV in urine using infrared spectroscopy.
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- DELTA study in Zambia (Treatment modalities in cervical screening in LMICs)
EPR is supporting the development and evaluation of a new battery-powered portable thermal ablator to treat cervical precancers, by comparing it with cryocautery and large loop excision of the transformation zone (LLETZ) to prevent cervical neoplasia, in a randomized controlled trial in Zambia (https://clinicaltrials.gov/ct2/show/NCT02956239). This new device avoids many of the practical disadvantages of cryotherapy, is preferred by health-care providers, and produces minimal complications or discomfort. The successful preliminary findings of this study have informed the recent WHO thermal ablation guidelines.
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- Zimbabwe randomized controlled trial to evaluate treatment time and use of analgesics for thermal ablation
WHO has recently recommended thermal ablation for treatment of cervical lesions, but there remain a few unresolved issues about the technique. The duration of application of the probe on the cervix varies from 20 to 60 seconds in previous studies, and no anaesthesia is used for the procedure. At least a few women (< 5%) experience moderate to severe pain during the procedure. EPR developed this new randomized controlled trial to evaluate treatment time and whether pain can be reduced by simple application of local anaesthetic (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=15741).
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- GUIDES (Facilitators and barriers for WHO cervical screening and treatment guidelines)
GUIDES aims to identify barriers and facilitators for the implementation of the WHO cervical cancer screening and treatment guidelines in specific local contexts and propose interventions to maximize the adoption and the fidelity of local implementation of the most up-to-date WHO guidelines. GUIDES will use the Consolidated Framework for Implementation Research (CFIR) to guide the interviewing of decision-makers, scientific societies, and health providers to understand their knowledge, their perceptions, and the acceptability of the implementation of guidelines.
- CARE4Afrique (Implementation and capacity-building for cervical cancer and breast cancer prevention)
EPR is supporting the implementation and evaluation of pilot projects using the visual inspection with acetic acid (VIA) screen-and-treat approach, and the increase of breast cancer early diagnosis capacity in Benin, Cameroon, Côte d’Ivoire, and Senegal. This study is also evaluating some novel approaches, such as the use of thermal ablation for the treatment of eligible screen-positive women and the introduction of HPV self-collection as a replacement for VIA (https://www.isrctn.com/ISRCTN21518741).
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- Interventions to improve participation in cervical cancer and breast cancer screening in France
The AppDateYou study aims to assess the impact of women’s informed decision-making through conversational artificial intelligence (a chatbot) to increase adherence to cervical cancer screening among non-respondent women. EPR is supporting the development and evaluation of a social network (CANelles) aimed to be used in the breast cancer screening programme in France, as a shared decision-making tool for women and general practitioners.
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- Colorectal cancer screening demonstration projects in LMICs
EPR is supporting the implementation of multicentre studies in Morocco, the Islamic Republic of Iran, and Saudi Arabia to evaluate the acceptability, feasibility, organization, implementation, monitoring, and evaluation of colorectal cancer screening in the general population setting by integrating the programme within the existing public health services to inform and guide the eventual scaling up of colorectal cancer screening to cover the entire country (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=5847).
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- BELUNGS (Implementation of pilot lung cancer screening in Belarus)
EPR is supporting this study to evaluate the development and implementation of a pilot programme for low-dose computed tomography (LDCT) lung cancer screening in Belarus (https://www.isrctn.com/ISRCTN16878075).
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- APACHES (Anal cancer natural history and screening)
EPR has a particular interest in the natural history and prevention of anal cancer, a cancer type that is rare in the general population but has an elevated incidence in established high-risk groups. APACHES is an ongoing prospective study of 500 HIV-positive men who have sex with men, in six centres in France. APACHES was designed particularly to answer essential questions about the progression and regression of high-grade anal lesions, and will evaluate the utility of several (bio)markers (including epigenetic) for anal cancer prevention (https://clinicaltrials.gov/ct2/show/NCT02287961).
Early diagnosis of common cancer types
- Assessment of cancer prevention in Morocco
The IMPACT study, based at the oncology centres in Rabat and Casablanca, is comparing breast cancer cases diagnosed within and outside the early diagnosis programme. The patterns-of-care study (patterns of care of patients with breast cancer and cervical cancer in Morocco) is evaluating the quality of care for women diagnosed with breast cancer and cervical cancer within the public health delivery system of Morocco. EPR is also helping to examine potential determinants of delayed referral in oncology centres in Morocco and the barriers to reaching cancer treatment facilities.
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- ABCDE India and Uganda (Evaluation of new technologies for breast cancer early diagnosis)
EPR is supporting the implementation of a multi-level, multi-component intervention strategy, including telepathology, a low-cost portable breast ultrasound device, and novel strategies such as molecular and histopathological diagnosis from cell blocks, to reduce access and diagnostic delays and improve the quality of diagnostic services for patients with breast cancer in India and Uganda.
- PUD-INDIA (Portable ultrasound device to triage clinical breast examination-positive women)
The aim of this study is to estimate the diagnostic accuracy of a low-cost, battery-powered portable ultrasound device (PUD) to triage which lumps need further evaluation from those that are clearly benign, and compare it with that of standards of care among clinical breast examination (CBE) screen-positive women. The use of the PUD can save CBE-positive women from unnecessary radiation, can lower costs, and can reduce the workload of radiologists. Non-radiologist clinicians can be trained to use the PUD to evaluate CBE-positive women.