The contribution of smoking and smokeless tobacco to oesophageal squamous cell carcinoma risk in the African oesophageal cancer corridor: Results from the ESCCAPE multicentre case-control studies.

Tobacco use is a well-established risk factor for oesophageal squamous cell carcinoma (ESCC) but the extent of its contribution to the disease burden in the African oesophageal cancer corridor has not been comprehensively elucidated, including by type of tobacco use. We investigated the contribution of tobacco use (smoking and smokeless) to ESCC in Tanzania, Malawi and Kenya. Hospital-based ESCC case-control studies were conducted in the three countries. Incident cases and controls were interviewed using a comprehensive questionnaire which included questions on tobacco smoking and smokeless tobacco use. Logistic regression models were used to estimate odds ratios (OR) and their 95% confidence intervals (CI) of ESCC associated with tobacco, adjusted for age, sex, alcohol use, religion, education and area of residence. One thousand two hundred seventy-nine cases and 1345 controls were recruited between August 5, 2013, and May 24, 2020. Ever-tobacco use was associated with increased ESCC risk in all countries: Tanzania (OR 3.09, 95%CI 1.83-5.23), and in Malawi (OR 2.45, 95%CI 1.80-3.33) and lesser in Kenya (OR 1.37, 95%CI 0.94-2.00). Exclusive smokeless tobacco use was positively associated with ESCC risk, in Tanzania, Malawi and Kenya combined (OR 1.92, 95%CI 1.26-2.92). ESCC risk increased with tobacco smoking intensity and duration of smoking. Tobacco use is an important risk factor of ESCC in Tanzania, Malawi and Kenya. Our study provides evidence that smoking and smokeless tobacco cessation are imperative in reducing ESCC risk.

A very-hot food and beverage thermal exposure index and esophageal cancer risk in Malawi and Tanzania: findings from the ESCCAPE case-control studies.

BACKGROUND: Consumption of very-hot beverages/food is a probable carcinogen. In East Africa, we investigated esophageal squamous cell carcinoma (ESCC) risk in relation to four thermal exposure metrics separately and in a combined score. METHODS: From the ESCCAPE case-control studies in Blantyre, Malawi (2017-20) and Kilimanjaro, Tanzania (2015-19), we used logistic regression models adjusted for country, age, sex, alcohol and tobacco, to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for self-reported thermal exposures whilst consuming tea, coffee and/or porridge. RESULTS: The study included 849 cases and 906 controls. All metrics were positively associated with ESCC: temperature of drink/food (OR 1.92 (95% CI: 1.50, 2.46) for 'very hot' vs 'hot'), waiting time before drinking/eating (1.76 (1.37, 2.26) for <2 vs 2-5 minutes), consumption speed (2.23 (1.78, 2.79) for 'normal' vs 'slow') and mouth burning (1.90 (1.19, 3.01) for ≥6 burns per month vs none). Amongst consumers, the composite score ranged from 1 to 12, and ESCC risk increased with higher scores, reaching an OR of 4.6 (2.1, 10.0) for scores of ≥9 vs 3. CONCLUSIONS: Thermal exposure metrics were strongly associated with ESCC risk. Avoidance of very-hot food/beverage consumption may contribute to the prevention of ESCC in East Africa.

Geophagia and risk of squamous cell esophageal cancer in the African esophageal cancer corridor: Findings from the ESCCAPE multicountry case-control studies.

Geophagia, the intentional practice of consuming soil, occurs across the African esophageal cancer corridor, particularly during pregnancy. We investigated whether this practice is linked to endemic esophageal squamous cell carcinoma (ESCC) in this region. We conducted ESCC case-control studies in Tanzania, Malawi and Kenya. Cases were patients with incident histologically/clinically confirmed ESCC and controls were hospital patients/visitors without digestive diseases. Participants were asked if they had ever eaten soil (never/regularly/pregnancy-only). Odds ratios (OR) are adjusted for sex, age, tobacco, alcohol, country, religion and marital status. Overall, 934 cases (Malawi 535, Tanzania 304 and Kenya females 95) and 995 controls provided geophagia information. Among controls, ever-geophagia was common in women (Malawi 49%, Kenya 43% and Tanzania 29%) but not in men (10% Malawi, <1% Tanzania). In women, ESCC ORs were 1.25 (95% CI: 0.70, 2.22) for regular versus never geophagia and 0.88 (95% CI: 0.64, 1.22) for pregnancy-only versus never. Findings were stronger based on comparisons of cases with hospital visitor controls and were null using hospital patients as controls. In conclusion, geophagia is too rare to contribute to the male ESCC burden in Africa. In women, the practice is common but we did not find consistent evidence of a link to ESCC. The study cannot rule out selection bias masking modest effects. Physical effects of geophagia do not appear to have a large impact on overall ESCC risk. Research with improved constituent-based geophagia exposure assessment is needed.

Mobile health-delivered narrative intervention to increase cervical cancer screening among Malawian women living with HIV: A pilot randomized controlled trial.

Objective: This study aimed to develop and evaluate a mobile health (mHealth)-delivered, theory-guided, culturally tailored storytelling narrative (STN) intervention to increase cervical cancer screening among Malawian women living with human immunodeficiency virus (HIV). Methods: This study involved two phases: Phase 1: development of a theory-guided and culturally adapted STN intervention and Phase 2: a pilot randomized controlled trial was conducted. Participants were randomly assigned to one of three arms: Arm 1: tablet-based video (mHealth) with STN (n = 60); Arm 2: mHealth with a video of nonnarrative educational materials (n = 59); and Arm 3: control group with only reading nonnarrative educational materials in person (n = 60). Cervical cancer screening was measured using visual inspection with acetic acid (VIA) uptakes by self-report and health passport record review at 2 and 6 months after intervention. Results: Both arms 1 and 2 had nearly twice the rate of VIA uptakes than those in Arm 3 (51.0% and 50.0%, respectively, vs. 35.0%, P = 0.01) at 2 months follow-up, but there were no differences among groups from 2- to 6-month follow-ups. All groups demonstrated significant improvement of knowledge about risk factors, intention, and VIA uptakes. Conclusions: The findings demonstrate the preliminary effectiveness of the intervention on cervical cancer screening behavior and the feasibility of the study regarding recruitment, retention, treatment fidelity, and acceptability of the single 30-min session. The feasibility and the preliminary results of the effectiveness of the proposed study indicate scaling up the STN intervention to a larger population of women to increase cervical cancer screening uptake to prevent deaths due to cervical cancer in Malawi.

Alcohol consumption and oesophageal squamous cell cancer risk in east Africa: findings from the large multicentre ESCCAPE case-control study in Kenya, Tanzania, and Malawi.

BACKGROUND: The contribution of alcohol to the large burden of oesophageal squamous cell carcinoma (ESCC) in east Africa remains uncertain and difficult to assess owing to complex consumption patterns of traditional and commercial drinks. We aimed to assess whether alcohol drinking, overall and at specific intake levels, contributes to ESCC risk in east Africa. METHODS: We did a hospital-based case-control study in Kenya, Tanzania, and Malawi, which included comprehensive assessment of a variety of locally consumed alcohol that we used to classify drinkers as exclusively low alcohol-by-volume (ABV; <30% ABV) drinkers or drinkers of some high-ABV drinks, as well as the number of drinks consumed, average weekly ethanol intake, and the contribution of each drink type to overall ethanol consumption. Cases were patients aged 18 years and older with incident primary ESCC, confirmed histologically for the majority of cases, and a clinical diagnosis for the remainder. Controls were frequency-matched on age and sex in a 1:1 ratio with cases. The controls were recruited from the same hospitals as cases and included outpatients, inpatients, and hospital visitors who did not have cancer or any other digestive disease. Consenting participants took part in face-to-face interviews in which they were asked whether they had ever consumed alcohol (the primary exposure variable); those who had were asked follow-up questions about their consumption habits for different alcoholic drinks. FINDINGS: 1279 cases and 1346 controls were recruited between Aug 5, 2013, and May 24, 2020, including 430 cases and 440 controls from Kenya, 310 cases and 313 controls from Tanzania, and 539 cases and 593 controls from Malawi. 65 (4·8%) of 1344 cases were excluded. Consistent positive associations with ESCC risk were found for ever having consumed alcohol in Kenyan men and Tanzanian men, and for daily number of drinks and estimated ethanol intake in Kenya, Tanzania (both sexes) and Malawian women. Corresponding population-attributable fractions of ESCC for those reporting ever drinking alcohol (vs never drinking) were 65% (95% CI 52-78) in Kenyan men and 23% (<1-45) in Kenyan women, and 56% (95% CI 36-76) in Tanzanian men and 5% (0-42) in Tanzanian women. Increased risk and population-attributable fractions were almost entirely due to risks in high-ABV drinkers. INTERPRETATION: Alcohol appears to be a substantial contributor to ESCC risk in east Africa, particularly among men, and a large fraction of ESCC could be prevented by cessation or reduction of alcohol consumption. Future studies should consider independent ascertainment of alcohol intake to assess the potential of under-reporting in Malawi. FUNDING: US National Cancer Institute, Wereld Kanker Onderzoek Fonds, and the IARC Environment and Lifestyle Epidemiology Branch. TRANSLATIONS: For the Swahili and Chichewa translations of the abstract see Supplementary Materials section.

A Malawi guideline for research study participant remuneration.

Background: Research participant remuneration has been variable and inconsistent world-wide for many years owing to uncertainty regarding best practice and a lack of written guidelines for investigators and research ethics committees.  Recent recommendations are that researchers and regulators should develop regionally appropriate written guidelines to define reasonable remuneration based on expense reimbursement, compensation for time and burden associated with participation.   Incentives to motivate participation are acceptable in specific circumstances. Methods: We wished to develop regionally informed, precise and applicable guidelines in Malawi that might also be generally useful for African researchers and review committees.  We therefore reviewed the current literature and developed widely applicable and specific remuneration tables using acceptable and evidence-based payment rationales. Results: There were good international guidelines and limited published regional guidelines.  There were published examples of best practice and sufficient material to suggest a structured remuneration table.  The rationale and method for the table were discussed at an inter-disciplinary workshop resulting in a reimbursement and compensation model with fixed rates.  Payment is recommended pro rata and equally across a study. Conclusions: Transparent, fair remuneration of research participants is recommended by researchers and regulators in Malawi.  The means to achieve this are now presented in the Malawi research participant remuneration table.

The African Esophageal Cancer Consortium: A Call to Action.

Esophageal cancer is the eighth most common cancer worldwide and the sixth most common cause of cancer-related death; however, worldwide incidence and mortality rates do not reflect the geographic variations in the occurrence of this disease. In recent years, increased attention has been focused on the high incidence of esophageal squamous cell carcinoma (ESCC) throughout the eastern corridor of Africa, extending from Ethiopia to South Africa. Nascent investigations are underway at a number of sites throughout the region in an effort to improve our understanding of the etiology behind the high incidence of ESCC in this region. In 2017, these sites established the African Esophageal Cancer Consortium. Here, we summarize the priorities of this newly established consortium: to implement coordinated multisite investigations into etiology and identify targets for primary prevention; to address the impact of the clinical burden of ESCC via capacity building and shared resources in treatment and palliative care; and to heighten awareness of ESCC among physicians, at-risk populations, policy makers, and funding agencies.

A framework for Controlled Human Infection Model (CHIM) studies in Malawi: Report of a Wellcome Trust workshop on CHIM in Low Income Countries held in Blantyre, Malawi.

Controlled human infection model (CHIM) studies have pivotal importance in vaccine development, being useful for proof of concept, pathogenesis, down-selection and immunogenicity studies.  To date, however, they have seldom been carried out in low and middle income countries (LMIC), which is where the greatest burden of vaccine preventable illness is found.  This workshop discussed the benefits and barriers to CHIM studies in Malawi.  Benefits include improved vaccine effectiveness and host country capacity development in clinical, laboratory and governance domains.  Barriers include acceptability, safety and regulatory issues. The report suggests a framework by which ethical, laboratory, scientific and governance issues may be addressed by investigators considering or planning CHIM in LMIC.

Subtyping sub-Saharan esophageal squamous cell carcinoma by comprehensive molecular analysis.

Esophageal squamous cell carcinoma (ESCC) is endemic in regions of sub-Saharan Africa (SSA), where it is the third most common cancer. Here, we describe whole-exome tumor/normal sequencing and RNA transcriptomic analysis of 59 patients with ESCC in Malawi. We observed similar genetic aberrations as reported in Asian and North American cohorts, including mutations of TP53, CDKN2A, NFE2L2, CHEK2, NOTCH1, FAT1, and FBXW7. Analyses for nonhuman sequences did not reveal evidence for infection with HPV or other occult pathogens. Mutational signature analysis revealed common signatures associated with aging, cytidine deaminase activity (APOBEC), and a third signature of unknown origin, but signatures of inhaled tobacco use, aflatoxin and mismatch repair were notably absent. Based on RNA expression analysis, ESCC could be divided into 3 distinct subtypes, which were distinguished by their expression of cell cycle and neural transcripts. This study demonstrates discrete subtypes of ESCC in SSA, and suggests that the endemic nature of this disease reflects exposure to a carcinogen other than tobacco and oncogenic viruses.

Oesophageal cancer and Kaposi's sarcoma in Malawi: a comparative analysis.

Given that oesophageal cancer (OC) is common in Malawi and its outcome is so dismal, would it be pragmatic to promptly mitigate the effects of smoking, alcohol and aflatoxins rather than seek a higher degree of local evidence for their role in OC? We retrospectively analysed a total of 13,217 OC and Kaposi's sarcoma (KS) cases as recorded in the Malawi National Cancer Registry from 1985 to February, 2006. We found no OC clustering to suggest a role for culturally variable habits like smoking, alcohol, maize use and maize storage in the country. It may be that drinking and eating hot foods physically damages the oesophageal mucosa, this is in line with work recently reported from Asia. We also found that OC numbers have risen in line with KS (and HIV) suggesting a link between these conditions.

Management of HIV associated Kaposi's sarcoma in Malawi.

Kaposi's sarcoma is a common malignancy in Malawi and is often managed with single agent vincristine. This article outlines feasible combination chemotherapy for Kaposi's sarcoma in Malawi which should be made more widely available.

The need for a national cancer policy in Malawi.

Cancer is causing a lot of suffering and death in Africa but is not considered a major health problem in Africa. This needs to change. Cancer should be given equal emphasis to HIV/AIDS, tuberculosis (TB) and Malaria. A national cancer policy is required in Malawi to develop and improve evidence-based cancer prevention, early diagnosis, curative and palliative therapy. A national cancer policy is crucial to ensure a priotised, clear, coordinated and sustained fight against cancer. When no policy exists, events are likely to be random, stakeholders and practitioners in the fight against cancer may not agree on how to proceed, may duplicate efforts or may neglect areas that would have greater nationwide impact resulting in poor quality activities and haphazard development.