THEMATIC AREA 1: Cancer Surveillance, Epidemiology and burden of disease
CARTA training is designed to enhance students’ skills and knowledge along the pathway to a PhD and to guide and propel them through the research process. As the facilitator or coordinator of PhD training in your institution, you can choose whether to:
Understanding local context (access to healthcare, surveillance, socio-economic and environmental challenges) in Africa is critical to developing strategies to address burden of disease. CARTA fellows choosing to work on this theme will geo-temporally map potential oncogenic infectious agents and layer those over geo-temporal cancer patterns in the context of evolving lifestyle cancer risk in sub-Saharan Africa (SSA). One specific workstream will be offered within this thematic area:
Project 1: Characterisation of oncogenic risk factors in sub-Saharan Africa
Project mentors and team: Judith Mwansa-Kambafwike (CARTA graduate), Mazvita Sengayi and Carl Chen (South Africa), Phiona Bukirwa (Uganda) and Lydia Businge (Rwanda).
Pathogens and toxins with oncogenic potential such as Schistosoma mansoni and haematobium, HIV (Sengayi-Muchengeti et al. 2023), and mycotoxins (Xue et al. 2019) have significant provincial variations within each country. Furthermore, demographic transitions and increases in smoking, obesity, alcohol use occurring in the three countries may affect associations between infections and cancer. Beyond cervical cancer, the oncogenic impact of HPV extends to head and neck, penile and anal cancers (Chikandiwa et al. 2019) and molecular and pathologic evidence
suggests a role in colorectal, oesophageal, prostate, lung and breast cancers. This presents opportunities to map potential oncogenic infectious agents and cancer patterns in the context of evolving lifestyle cancer risk. Objectives include: (i) Scoping: To identify sources of data for infectious agents in areas with existing population-based cancer registries, (ii) Environmental: To map prevalence data of infectious agents of interest with cancer data for hypothesis generation, and (iii) Individual: To characterize associations between HIV, HPV, mycotoxins, malaria, TB, Schistosomiasis, and other infections and risk factors and specific cancers.
This hypotheses-generating work will be conducted in an exploratory, phased manner to investigate novel associations between cancer and infectious factors. Fellows may choose a cancer of interest to work on (i.e. S. mansoni in colorectal and liver cancer, S. haematobium in bladder cancer, HPV and multiple cancers, malaria and EBV in Burkitt’s lymphoma, mycotoxins and oesophageal cancer).
Findings from this pilot work would form the foundation for a multi-country, multi-disciplinary, well-funded proposal to investigate the pathogen-cancer relationship; designed, written and submitted by a CARTA fellow, in conjunction with DISCOURSE mentors, at the end of year 2. The goal would be to identify novel approaches for diagnosing, preventing and treating a high burden cancer.
THEMATIC AREA 2: Cancer Screening and early diagnosis
CARTA training is designed to enhance students’ skills and knowledge along the pathway to a PhD and to guide and propel them through the research process. As the facilitator or coordinator of PhD training in your institution, you can choose whether to:
Cancer screening and diagnosis are important components of the cancer control continuum. Effective screening can reduce the incidence and improve the prognosis of cancers. Lack of cancer screening and diagnostics infrastructures are stumbling blocks for cancer control in SSA.
Project 2: Cervical cancer (CC) screening and early diagnosis
Project mentors and team: Carole Metekoua (South Africa), Judith Mwansa-Kambafwike and Admire Chikandiwa (CARTA graduates, South Africa), Henry Zakumumpa (CARTA graduate, Uganda), Athanase Munyaneza (Rwanda).
This project characterises existing CC screening and diagnostic capacity in Uganda, Rwanda, and South Africa. Objectives include: (i) Identifying the approaches, technologies, and human resources available for screening and diagnosis of CC in the three countries using local and global sources (e.g. gap analysis from the global CanScreen5 assessment conducted in Rwanda), (ii) Mapping distribution, accessibility and effectiveness of CC screening and diagnosis resources (e.g. distance to the healthcare facility, cost to the patient and/or treatment turnaround time), and (iii) Estimating the level of under-diagnoses. Describe cost effectiveness and feasibility of options to improve CC screening and diagnosis in each country. With objectives achieved, fellow(s) will be positioned to design a high-value, multi-country study to test interventions to strengthen screening.
Project 3: Investigating factors responsible for low uptake of cervical cancer screening in Rwanda
Project mentors and team: Athanase Munyaneza and Marc Hagenima (Rwanda).
CC screening coverage among high-risk eligible women is extremely low: 14-20% in most of Africa (Gafaranga et al. 2022). This country-specific project will identify fundamental factors contributing to low uptake of CC screening in Rwanda. CC screening data (from clinics) will be integrated with the National Cancer Registry (NCR) database to identify CC cases that did not undergo screening. CC cases identified through screening will be compared with unscreened cases to identify promotive and risk factors for cancer screening. The fellow will use the findings from this study to design interventions to address identified factors, leading to a multi-country (co-designed) implementation science proposal to evaluate impacts of implementing the interventions in rural and urban settings in multiple countries.
THEMATIC AREA 3: Factors impacting cancer treatment effectiveness and survival
Incident and mortality data on cervical cancer (CC) are understudied in SSA. Two proposed projects will utilise an existing cohort of ~1500 women diagnosed with CC in 2021-2022 and treated at the Charlotte Maxeke Johannesburg Academic Hospital Radiation Oncology Department (CMH), (hereafter known as the “CMH cohort”). One project will address barriers to early detection (Tshabalala et al. 2023) and the other will examine use of biomarkers for management and prognosis.
Project 4: Describing treatments received by HIV+ and HIV- patients in investigating 2-yr overall cervical cancer survival
Project mentors and team: Oluwatosin Ayeni and Maureen Joffe (South Africa) and Judith Mwansa-Kambafwile (CARTA graduate, South Africa).
This project will describe the socio-demographic and clinical characteristics of the CMH cohort and will assess determinants of stage at diagnosis (including barriers to screening and timely treatment) using regression analysis. It will then compare 2-year overall survival among HIV-positive and HIV-negative patients by treatment received (i.e. conservative, surgical, chemotherapy and radiotherapy) using Kaplan Meyer plots and hazard ratio assessment for survival determinants.
This pilot research will provide the foundational evidence to design a multi-country clinic-epidemiologic proposal to initiate implementation science research to develop and test interventions to increase CC screening rates and for specific clinical management approaches (based on stage and risk factors) to improve clinical outcomes.
Project 5: Identifying performance biomarkers in predicting progression of cervical HSILs and overall cervical cancer survival
Project mentors and team: Admire Chikandiwa (CARTA graduate, Wits University), Maureen Joffe (Wits University).
Clinical biomarkers could improve early detection and management of high-grade squamous intra-epithelial lesions (HSILs) and CC. Biomarkers might have prognostic (i.e. predict disease course) and predictive value (i.e. predict clinical effect, relapse-free period, survival, sensitivity to treatment) which will help to triage patients to specific therapies.
The CARTA fellow will have the opportunity to utilize the existing CMH cohort data set. The cohort study objective is to describe treatments received and compare 2-year overall survival among HIV-positive and HIV-negative patients from the retrospective cohort. The fellow (working with mentors) will establish two sub-cohorts: a) women with high-grade squamous intraepithelial lesions (HSIL) (pre-cancerous, associated with HPV); b) women diagnosed with CC. The fellow will evaluate roles of biomarkers, including p16INK4a, Ki-67, Cyclin D1, P53 and BCL-2, VEGF, CK7 and CK8, and the diversity of the cervicovaginal microbiome. Samples will be from large loop excision of the transformation zone (LLETZ) excisional biopsy in HSIL, or a punch biopsy in the case of invasive CC.
