Barriers to cervical cancer screening in Africa: a systematic review.

INTRODUCTION: Africa has one of the highest burdens of cervical cancer in the world. The unacceptably high incidence and mortality rates could be reduced through implementing a comprehensive approach to its prevention and control that includes screening, which however, is low in most low-and-middle-income countries. Hence, this systematic review aims at exploring factors that prevent women from utilising cervical cancer screening services in the region. METHODS: A mixed method systematic review was conducted. A search was performed on PubMed (Medline), EMBASE, CINAHL (EBSCOHOST) and Scopus databases for articles published until May 2019 without time, language or study design limits. Two reviewers critically appraised the included studies independently using the standard quality assessment criteria for evaluating primary research papers. Results of the quantitative and mixed methods studies were transformed into qualitative data and synthesised using thematic analysis. RESULTS: From a potential 2 365 studies, 24 from 11 countries met the eligibility criteria and were selected; eight qualitative, 13 quantitative, and three that used the mixed-method approach. The primary barriers were identified as poor access to screening services, lack of awareness and knowledge on cervical cancer and screening, and socio-cultural influences. Service providers perceived lack of skills, screening equipment and supplies, and staff shortages as the major barriers to the provision of screening services. CONCLUSION: Barriers to cervical cancer screening in Africa are multifaceted and require a holistic approach that will address them concurrently at the health system, individual, interpersonal, community and structural levels. Political will complimented by stakeholder involvement is required in the development and implementation of strategies that will ensure acceptability, availability, accessibility, and affordability of screening to minimise barriers in accessing the service.

Africa Guidelines for Hepatocellular Carcinoma Buildup Process.

PURPOSE: Hepatocellular carcinoma (HCC), the fourth most common cancer in Africa, has a dismal overall survival of only 3 months like in sub-Saharan Africa. This is affected by the low gross domestic product and human development index, absence of coherent guidelines, and other factors. METHODS: An open forum for HCC-experienced health care workers from Africa and the rest of the world was held in October 2021. Participants completed a survey to help assess the real-life access to screening, diagnoses, and treatment in the North and Southern Africa (NS), East and West Africa (EW), Central Africa (C), and the rest of the world. RESULTS: Of 461 participants from all relevant subspecialties, 372 were from Africa. Most African participants provided hepatitis B vaccination and treatment for hepatitis B and C. More than half of the participants use serum alpha-fetoprotein and ultrasound for surveillance. Only 20% reported using image-guided diagnostic liver biopsy. The Barcelona Clinic Liver Cancer is the most used staging system (52%). Liver transplant is available for only 28% of NS and 3% EW. C reported a significantly lower availability of resection. Availability of local therapy ranged from 94% in NS to 62% in C. Sorafenib is the most commonly used systemic therapy (66%). Only 12.9% reported access to other medications including immune checkpoint inhibitors. Besides 42% access to regorafenib in NS, second-line treatments were not provided. CONCLUSION: Similarities and differences in the care for patients with HCC in Africa are reported. This reconfirms the major gaps in access and availability especially in C and marginally less so in EW. This is a call for concerted multidisciplinary efforts to achieve and sustain a reduction in incidence and mortality from HCC in Africa.

Environmental and life-style risk factors for esophageal squamous cell carcinoma in Africa: a systematic review and meta-analysis.

BACKGROUND: The African Esophageal Squamous Cell Carcinoma (ESCC) corridor, which spans from Ethiopia down to South Africa, is an esophageal cancer hotspot. Disproportionately high incidence and mortality rates of esophageal cancer have been reported from this region. The aim of this study was to systematically assess the evidence on environmental and life-style risk factors associated with ESCC in African populations. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and carried out a comprehensive search of all African published studies up to March 2023 using PubMed, Embase, Scopus, and African Index Medicus databases. RESULTS: We identified 45 studies with measures of association [odds ratio (OR), relative risk (RR), and 95% confidence intervals (95%CI)], which reported on several environmental and lifestyle risk factors for ESCC in Africa. We performed a meta-analysis on 38 studies investigating tobacco, alcohol use, combined tobacco and alcohol use, polycyclic aromatic hydrocarbon exposure, hot food and beverages consumption (which served as a proxy for esophageal injury through exposure to high temperature), and poor oral health. We found significant associations between all the risk factors and ESCC development. Analysis of fruit and vegetable consumption showed a protective effect. Using population attributable fraction (PAF) analysis, we calculated the proportion of ESCC attributable to tobacco (18%), alcohol use (12%), combined tobacco and alcohol use (18%), polycyclic aromatic hydrocarbon exposure (12%), hot food and beverages intake (16%), poor oral health (37%), and fruit and vegetable consumption (-12%). CONCLUSIONS: Tobacco smoking and alcohol consumption were the most studied risk factors overall. Areas where there is an emerging body of evidence include hot food and beverages and oral health. Concurrently, new avenues of research are also emerging in PAH exposure, and diet as risk factors. Our results point to a multifactorial etiology of ESCC in African populations with further evidence on prevention potential.

Cisplatin-associated ototoxicity amongst cervical cancer patients: A prospective cohort study in south Africa.

BACKGROUND: Concurrent chemoradiotherapy using weekly cisplatin remains standard of care for locally advanced cervical cancer in Sub-Saharan Africa. While cisplatin remains a popular cancer chemotherapeutic, it has an irreversible ototoxic effect on patients' auditory system. However, there is a paucity of epidemiological information on its extent and severity during cervical cancer treatment. In a region with a high burden of cervical cancer, this has serious consequences for aural intervention and rehabilitation. METHODS AND FINDINGS: Using a prospective cohort study design, 82 patients with incident cervical cancer, receiving weekly cisplatin chemotherapy (50 mg/m2 body surface) at a tertiary level hospital in KwaZulu-Natal Province of South Africa, underwent audiological assessments at various intervals. We describe the temporal impact of cisplatin exposure on hearing loss, its combined effect with HIV-infection, and estimate ototoxicity incidence in this cohort. The median age was 52 years with Stages IIB (45%) and IIIB (35.4%) cancers being most common. Complaints of reduced hearing sensitivity increased significantly (p<0.0001). Bilateral, asymmetrical sensorineural hearing loss, with greater effect in the extended high-frequency range, was evident. Cisplatin dosage was significantly associated with ototoxicity severity at one- (p = 0.017), three- (p = 0.010), and six-month (p = 0.015) post-treatment follow-up. HIV-seropositivity (53.7%) was significantly associated with NCI-CTCAE Grading Scale at three- (p = 0.022) and six-months (p = 0.023) post-treatment. Multiple Tobit regression revealed a cumulative dose effect bilaterally, after adjustment for age and HIV status, evident from 9000Hz and above in the right ear, while a plateau effect was observed at 250mg/m2 in the left ear. The incidence was ototoxicity was 98% at a cumulative dose of 150mg/m2. CONCLUSION: The findings of this epidemiologic study highlight the temporal course and severity of ototoxicity experienced by cervical cancer patients treated with cisplatin, with greater impact in HIV-positive subgroup, thus underscores the need for audiological monitoring and timely interventions in this cohort.

The carcinogenicity of opium consumption: a systematic review and meta-analysis.

The carcinogenicity of opium consumption was recently evaluated by a Working Group convened by the International Agency for Research on Cancer (IARC). We supplement the recent IARC evaluation by conducting an extended systematic review as well as a quantitative meta-analytic assessment of the role of opium consumption and risk for selected cancers, evaluating in detail various aspects of study quality on meta-analytic findings. We searched the published literature to identify all relevant studies on opium consumption and risk of selected cancers in humans through 31 October, 2022. Meta-relative risks (mRRs) and associated 95% confidence intervals (CIs) were estimated using random-effects models for studies of cancer of the urinary bladder, larynx, lung, oesophagus, pancreas, and stomach. Heterogeneity among studies was assessed using the I2 statistic. We assessed study quality and conducted sensitivity analyses to evaluate the impact of potential reverse causation, protopathic bias, selection bias, information bias, and confounding. In total, 2 prospective cohort studies and 33 case-control studies were included. The overall pooled mRR estimated for 'ever or regular' versus 'never' use of opium ranged from 1.50 (95% CI 1.13-1.99, I2 = 0%, 6 studies) for oesophageal cancer to 7.97 (95% CI 4.79-13.3, I2 = 62%, 7 studies) for laryngeal cancer. Analyses of cumulative opium exposure suggested greater risk of cancer associated with higher opium consumption. Findings were robust in sensitivity analyses excluding studies prone to potential methodological sources of biases and confounding. Findings support an adverse association between opium consumption and cancers of the urinary bladder, larynx, lung, oesophagus, pancreas and stomach.

Cisplatin-associated ototoxicity: perspectives from a single institution cervical cancer cohort and implications for developing a locally responsive monitoring programme in a public healthcare setting.

BACKGROUND: Ototoxicity monitoring is uncommon in South Africa, despite the increased use of ototoxic medication to manage the burden of disease in the country. The successful implementation of such a protocol requires cognisance of contextual realities and multiple dimensions for consideration from both patients and service providers. As part of an ongoing cohort study on cisplatin-associated ototoxicity and efforts to better inform the implementation of such programmes, the perspectives of cervical cancer patients and healthcare workers towards ototoxicity monitoring were assessed. METHODS: This concurrent-triangulation mixed-methods study was conducted at a tertiary hospital in South Africa. Self-reported questionnaires from patients (n = 80) and healthcare personnel comprising clinicians, oncology nurses, pharmacists, and radiotherapists (n = 32), results of audiological evaluations, researcher field notes, and estimated patient and service provider costs contributed to data for this study. Data analysis included descriptive statistics, comparison of test characteristics and deductive thematic analysis. RESULTS: The ototoxicity monitoring programme was positively received by the participants, with 90.6% of healthcare personnel and 89% of patients reporting it to be beneficial. The clinicians (76.6%) were identified as the main providers of information on the effects of chemotherapy medication and made the necessary referrals for audiological evaluation. The approximate cost of setting up such a programme included purchase of equipment (US56 700) and the appointment of an audiologist (US 26 250). The approximate costs to patients included transport costs (US$ 38) and the loss of income for the day (US 60), calculated at the minimum wage per hour, if employed. Creative appointment scheduling, easy facility access and detailed locally comprehensible couselling improved patient compliance to the programme. Whilst the sequential use of American Speech-Language-Hearing Association (ASHA) and National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria aided in an evidence-informed approach to aural rehabilitation, DPOAEs and speech discrimination displayed low sensitivity (range 1.45% - 22.39%) but high specificity (range 77.78% - 100%) when identifying ototoxic change. CONCLUSION: This novel study, through a 'real-world' experience, has revealed that an ototoxicity monitoring programme is feasible in South Africa, through meaningful engagements with- and considerations from- patients and service providers regarding planning, delineation of responsibilities and cost implications. The findings can potentially serve as a roadmap for other limited resource environments.

Centella asiatica Modulates Nrf-2 Antioxidant Mechanisms and Enhances Reactive Oxygen Species-Mediated Apoptotic Cell Death in Leukemic (THP-1) Cells.

Centella asiatica is commonly used in traditional medicine owing to its many therapeutic properties including but not limited to antioxidant and antitumor potential. This study examined the antioxidant and antiproliferative effects of its crude (C) and fractionated (C3) ethanolic leaf extracts in THP-1 cells. In THP-1 cells, C and C3 cytotoxicity was evaluated (WST-1 viability assay; 24 h; [0.2-3 mg/mL]) and half maximal inhibitory concentration was obtained. Malondialdehyde (MDA; spectrophotometry), mitochondrial depolarization (Δψm), intracellular reactive oxygen species (IROS; flow cytometry), glutathione (GSH), oxidized GSH (GSSG) concentrations, adenosine triphosphate (ATP) levels, caspase activities (luminometry) and DNA fragmentation (single cell gel electrophoresis assay) were evaluated. Protein expression and gene expression was quantified by Western blotting and quantitative polymerase chain reaction, respectively. THP-1 cell viability was dose-dependently reduced by C and C3. MDA, IROS, GSH, and Δψm were increased and ATP was decreased by C and C3 (P < .01). Antioxidant gene expression, Nrf-2 protein expression, and GSSG levels (P < .01) were increased by C, but were decreased by C3. C and C3 elevated caspase activity and DNA damage (P < .0001), whereas they decreased glutathione peroxidase and Bcl-2 protein expressions (P < .003). c-PARP protein expression and c-myc gene expression was decreased by C, whereas they were increased by C3 (P < .002). C3 reduced OGG-1 gene expression (P < .0003). Antioxidant responses were increased by C, whereas they were decreased by C3. Both C and C3 exerted antiproliferative effects in THP-1 cells by enhancing apoptosis. Of note, C3 more effectively induced apoptosis.

A comparison of clinicopathologic features of prostate cancer between Nigerian and South African black men.

Background: Globally, prostate cancer (PCa) is the commonest non-cutaneous male malignancy. It is more aggressive among black men with little known reasons as to the cause and continued trend among black men. This disproportionate pattern of PCa especially among black men of African ancestry resident in Africa calls for a closer look. Nigeria and South Africa, combined, have the highest cumulative risk incidence of PCa in Africa. The present study investigated the clinicopathologic behaviour of PCa among Nigerian and South African black men and the relationship between the disease and socio-demographic characteristics alongside medical co-morbidities. Methods: A retrospective cross-sectional study was undertaken in which de-identified records of 234 black men with pathologically confirmed PCa between 2007 and 2017 from two tertiary hospitals, in Nigeria (National Hospital, Abuja) and South Africa (Tygerberg Hospital, Cape Town), were reviewed. Results: Median age at presentation from both countries was 66 years (interquartile range, IQR 61-73 years) while the median PSA at presentation was 46 ng/ml (IQR 16-336.5 ng/ml). Half of the men (117/234) presented with locally advanced disease while metastatic disease was observed in 65.9% (27/41) of Nigerian men and 34.1% (14/41) of South African men. Thirty-three per cent of the men presented with organ-confined disease. Overall, Nigerian men presented with less organ-confined disease and significantly higher stage of disease (p < 0.001). Risk stratification using PSA, Gleason scores and T-staging showed that 84.2% (n = 197) of all the men presented with high-risk PCa disease. There was a statistically significant difference between Nigerian and South African black men (p = 0.003) in terms of disease risk at presentation. Logistic regression analysis showed that age (Adjusted OR 1.053 (95% CI 1.003-1.106), p = 0.003) and country of residence (Adjusted OR 4.281 (95% CI 1.690-10.844), p = 0.002) had a statistically significant relationship with high risk of PCa while disease co-morbidities (like diabetes and hypertension) and rural/urban location in both countries did not. Conclusions: Disparities exist between PCa presentation and clinicopathologic behaviour among Nigerian and South African black men. Nigerian men showed higher disease risk at presentation. Environmental-genetic interactions need further exploration in the aetio-pathogenesis of PCa in black men of African ancestry.

Feasibility and first results of a prospective cohort study to investigate cisplatin-associated ototoxicity amongst cancer patients in South Africa.

BACKGROUND: Cervical cancer, one of the most common cancers affecting females in South Africa, commonly requires a cisplatin-based-treatment regimen, which has been associated with ototoxic side effects. However, cisplatin-associated ototoxicity is largely under-reported in South Africa, despite its impact of hearing loss having serious overt ramifications on the quality of life of these patients. Hence, a prospective cohort study was undertaken to assess the audiological changes in female cervical cancer patients receiving cisplatin therapy. OBJECTIVE: To present details of the feasibility study and initial results on hearing patterns in cervical cancer patients receiving cisplatin chemotherapy. . METHODS: Fifty cervical cancer patients commencing with cisplatin chemotherapy underwent audiological assessments at a hospital in South Africa at various time intervals. Assessments included case history, otoscopic examination, immittance audiometry, pure tone audiometry (including high-frequency audiometry), speech audiometry, and distortion product otoacoustic emission testing. Data analysis involved the use of descriptive statistics and the Cochran-Armitage trend test for a linear trend in proportions. RESULTS: Fifty participants, aged between 32 and 79 years (Mean: 53 years; SD = 11.00), were recruited. Clinical findings revealed an incidence of 100% ototoxic hearing loss at the one-month post-treatment, i.e., 98%  after three cycles of cisplatin and 2%  at one-month post-chemotherapy. Sensorineural hearing loss and high-frequency tinnitus were most common. Deterioration in hearing thresholds was more evident in the extended high-frequency range, with the number of "no-responses," from 11,200 Hz to 20,000 Hz, increasing with each successive audiological evaluation. This study further indicated that recruitment and follow-up of study participants within a limited resource setting are possible. However, cognizance must be given to a multidisciplinary approach and constant engagement with participants through regular contact either telephonically or via a short-message-system. CONCLUSION: Exposure to cisplatin treatment contributed to hearing loss in females with cervical cancer, highlighting the need for ototoxicity monitoring during chemotherapy treatments. Furthermore, the results indicate that it is possible to conduct prospective cohort studies, using a multidisciplinary approach in limited-resource environments with appropriate planning and training strategies, as this study was able to achieve its aim successfully.

Hepatocellular Carcinoma in Sub-Saharan Africa.

More than 80% of global hepatocellular carcinoma (HCC) patients are estimated to occur in sub-Saharan Africa (SSA) and Eastern Asia. The most common risk factor of HCC in SSA is chronic hepatitis B virus (HBV) infection, with the incidence highest in West Africa. HBV is highly endemic in SSA and is perpetuated by incomplete adherence to birth dose immunization, lack of longitudinal follow-up care, and impaired access to antiviral therapy. HBV may directly cause HCC through somatic genetic alterations or indirectly through altered liver function and liver cirrhosis. Other risk factors of HCC in SSA include aflatoxins and, to a lesser extent, African iron overload. HIV plus HBV co-infection increases the risk of developing HCC and is increasingly becoming more common because of improving the survival of patients with HIV infection. Compared with the rest of the world, patients with HCC in SSA have the lowest survival. This is partly due to the late presentation of HCC with advanced symptomatic disease as a result of underdeveloped surveillance practices. Moreover, access to care and resource limitations further limit outcomes for the patients who receive a diagnosis in SSA. There is a need for multipronged strategies to decrease the incidence of HCC and improve its outcomes in SSA.

Baseline audiological profiling of South African females with cervical cancer: an important attribute for assessing cisplatin-associated ototoxicity.

BACKGROUND: Cisplatin is a popular antineoplastic agent used to treat cervical cancer in women from low and middle-income countries. Cisplatin treatment is associated with ototoxicity, often resulting in hearing loss. In light of this, it is crucial to conduct baseline audiological assessments prior to treatment initiation in order to evaluate the extent of cisplatin-associated-ototoxicity. Additionally, the identification of inherent risk factors and hearing patterns in specific patient cohorts is needed, especially in South Africa, a middle-income country characterized by the quadruple burden of disease (Human Immunodeficiency Virus (HIV), Tuberculosis (TB), Diabetes and Hypertension). METHODS: This study aimed to describe a profile of risk factors and hearing in a cohort of females with cervical cancer before cisplatin treatment commenced. A descriptive study design that included 82 cervical cancer patients, who underwent audiological evaluation prescribed for ototoxicity monitoring was conducted. RESULTS: All participants (n = 82) presented with risk factors (diabetes, hypertension, HIV, and antiretroviral therapy) for cisplatin ototoxicity and/or pre-existing sensorineural hearing loss. High-frequency tinnitus was the most common otological symptom experienced by 25 (31%) participants. Fifty-nine (72%) participants presented with normal hearing, twenty-two (27%) with a sensorineural hearing loss, and 36% were diagnosed with mild hearing loss. Abnormal Distortion Product Otoacoustic Emissions (DPOAE) findings were obtained bilaterally in two participants (2.4%), in the right ear only of another two (2.4%) participants and the left ear of three participants (3.7%). Most participants (94%) had excellent word recognition scores, demonstrating an excellent ability to recognize words within normal conversational levels under optimal listening conditions. Age was significantly associated with hearing loss at all thresholds. Among the co-morbidities, an HIV positive status significantly triggered hearing loss, especially at higher frequencies. CONCLUSION: This study demonstrated that South African females with cervical cancer present with various co-morbidities, which may predispose them to develop cisplatin-associated -ototoxic hearing loss. Identification of these co-morbidities and hearing loss is essential for the accurate monitoring of cisplatin toxicities. Appropriate management of these patients is pivotal to reduce the adverse effects that hearing impairment can have on an individual's quality of life and to facilitate informed decision-making regarding the commencement of cisplatin chemotherapy.

Neighborhood greenness and burden of non-communicable diseases in Sub-Saharan Africa: A multi-country cross-sectional study.

Population growth, demographic transitions and urbanization in sub-Saharan Africa (SSA) will increase non-communicable disease (NCD) burden. We studied the association between neighborhood greenness and NCDs in a multi-country cross-sectional study. Among 1178 participants, in adjusted models, a 0.11 unit NDVI increase was associated with lower BMI (ß: -1.01, 95% CI: -1.35, -0.67), and lower odds of overweight/obesity (aOR: 0.73, 95% CI: 0.62, 0.85), diabetes (aOR: 0.77, 95% CI: 0.62, 0.96), and having ≥3 allostatic load components compared to none (aOR: 0.66, 95% CI: 0.52, 0.85). Except for diabetes, these remained statistically significant after Bonferroni correction. We observed no association between NDVI and hypertension or cholesterol. Our findings are consistent with health benefits of neighborhood greenness reported in other countries, suggesting greening strategies could be considered as part of broader public health interventions for NCDs.

Clinical Trials for Treatment and Prevention of HIV-Associated Malignancies in Sub-Saharan Africa: Building Capacity and Overcoming Barriers.

PURPOSE: The aim of this study was to review the current status of clinical trials for HIV-associated malignancies in people living with HIV in sub-Saharan Africa (SSA) and efforts made by the AIDS Malignancy Consortium (AMC) to build capacity in SSA for HIV malignancy research. METHODS: All malignancy-related clinical trials in 49 SSA countries on ClinicalTrials.gov were reviewed and evaluated for inclusion and exclusion criteria pertaining to HIV status. Additional studies by AMC in SSA were compiled from Web-based resources, and narrative summaries were prepared to highlight AMC capacity building and training initiatives. RESULTS: Of 96 cancer trials identified in SSA, only 11 focused specifically on people living with HIV, including studies in Kaposi sarcoma, cervical dysplasia and cancer, non-Hodgkin lymphoma, and ocular surface squamous neoplasia. Recognizing the increasing cancer burden in the region, AMC expanded its clinical trial activities to SSA in 2010, with 4 trials completed to date and 6 others in progress or development, and has made ongoing investments in developing research infrastructure in the region. CONCLUSION: As the HIV-associated malignancy burden in SSA evolves, research into this domain has been limited. AMC, the only global HIV malignancy-focused research consortium, not only conducts vital HIV-associated malignancies research in SSA, but also develops pathology, personnel, and community-based infrastructure to meet these challenges in SSA. Nonetheless, there is an ongoing need to build on these efforts to improve HIV-associated malignancies outcomes in SSA.

Perspectives and practices of ototoxicity monitoring.

BACKGROUND: Treatment of cancer with cisplatin can result in hearing loss. Given the increasing burden of cancer in Africa, appropriate and timely identification, intervention and management of hearing loss in affected patients is of paramount importance. OBJECTIVES: This study describes the perspectives and practices of healthcare professionals in relation to cisplatin-associated ototoxicity at an institution treating patients diagnosed with cancer. METHOD: A concurrent triangulation study design was used to collect quantitative data from seven oncologists, nine nurses and 13 pharmacists using self-administered questionnaires, and qualitative data from four audiologists through semi-structured interviews for this hospital-based study, conducted in South Africa. RESULTS: Levels of awareness of cisplatin-associated ototoxicity varied with only 33% of the nursing personnel being aware in comparison to the oncologists and pharmacists. Oncologists were identified as the main custodians for providing information to patients. Whilst 82% of the participants considered the audiologist to be part of the oncology team, there was no provision for ototoxicity monitoring in the chemotherapy protocols, nor any ototoxicity-monitoring programme in place. There was no evidence that knowledge of cisplatin-associated ototoxicity translated into an appropriate management strategy for such patients. CONCLUSION: Healthcare personnel overseeing the care and management of cancer patients need to improve their awareness of ototoxicity and refer timeously for audiological evaluation. Audiologists require greater awareness of monitoring programmes to appropriately implement and manage such programmes within a cancer platform and be part of a multidisciplinary team.

Systematic Review of Genetic Factors in the Etiology of Esophageal Squamous Cell Carcinoma in African Populations.

Background: Esophageal squamous cell carcinoma (ESCC), one of the most aggressive cancers, is endemic in Sub-Saharan Africa, constituting a major health burden. It has the most divergence in cancer incidence globally, with high prevalence reported in East Asia, Southern Europe, and in East and Southern Africa. Its etiology is multifactorial, with lifestyle, environmental, and genetic risk factors. Very little is known about the role of genetic factors in ESCC development and progression among African populations. The study aimed to systematically assess the evidence on genetic variants associated with ESCC in African populations. Methods: We carried out a comprehensive search of all African published studies up to April 2019, using PubMed, Embase, Scopus, and African Index Medicus databases. Quality assessment and data extraction were carried out by two investigators. The strength of the associations was measured by odds ratios and 95% confidence intervals. Results: Twenty-three genetic studies on ESCC in African populations were included in the systematic review. They were carried out on Black and admixed South African populations, as well as on Malawian, Sudanese, and Kenyan populations. Most studies were candidate gene studies and included DNA sequence variants in 58 different genes. Only one study carried out whole-exome sequencing of 59 ESCC patients. Sample sizes varied from 18 to 880 cases and 88 to 939 controls. Altogether, over 100 variants in 37 genes were part of 17 case-control genetic association studies to identify susceptibility loci for ESCC. In these studies, 25 variants in 20 genes were reported to have a statistically significant association. In addition, eight studies investigated changes in cancer tissues and identified somatic alterations in 17 genes and evidence of loss of heterozygosity, copy number variation, and microsatellite instability. Two genes were assessed for both genetic association and somatic mutation. Conclusions: Comprehensive large-scale studies on the genetic basis of ESCC are still lacking in Africa. Sample sizes in existing studies are too small to draw definitive conclusions about ESCC etiology. Only a small number of African populations have been analyzed, and replication and validation studies are missing. The genetic etiology of ESCC in Africa is, therefore, still poorly defined.

A Review of Cisplatin-Associated Ototoxicity.

Cisplatin, an effective antineoplastic drug used in the treatment of many cancers, has ototoxic potential, thus placing cancer patients, receiving this treatment, at risk of hearing loss. It is therefore important for health care professionals managing these patients to be aware of cisplatin's ototoxic properties and its clinical signs to identify patients at risk of developing a hearing impairment. Eighty-five English peer-reviewed articles and two books, from January 1975 to July 2015, were identified from PubMed, ScienceDirect, and EBSCOhost. An overview of cisplatin-associated ototoxicity, namely its clinical features, incidence rates, molecular and cellular mechanisms, and risk factors, is presented in this article. This review further highlights the importance of a team-based approach to complement an audiological monitoring program in reducing any further loss in the quality of life of affected patients, as there is currently no otoprotective agent routinely recommended for the prevention of cisplatin-associated ototoxicity.

Withania somnifera modulates cancer cachexia associated inflammatory cytokines and cell death in leukaemic THP-1 cells and peripheral blood mononuclear cells (PBMC's).

BACKGROUND: Cancer and inflammation are associated with cachexia. Withania somnifera (W. somnifera) possesses antioxidant and anti-inflammatory potential. We investigated the potential of an aqueous extract of the root of W. somnifera (WRE) to modulate cytokines, antioxidants and apoptosis in leukaemic THP-1 cells and peripheral blood mononuclear cells (PBMC's). METHODS: Cytotoxcity of WRE was determined at 24 and 72 h (h). Oxidant scavenging activity of WRE was evaluated (2, 2-diphenyl-1 picrylhydrazyl assay). Glutathione (GSH) levels, caspase (- 8, - 9, - 3/7) activities and adenosine triphosphate (ATP) levels (Luminometry) were thereafter assayed. Tumour necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1ß and IL-10 levels were also assessed using enzyme-linked immunosorbant assay. RESULTS: At 24 h, WRE (0.2-0.4 mg/ml) decreased PBMC viability between 20 and 25%, whereas it increased THP-1 viability between 15 and 23% (p < 0.001). At 72 h, WRE increased PBMC viability by 27-39% (0.05, 0.4 mg/ml WRE) whereas decreased THP-1 viability between 9 and 16% (0.05-0.4 mg/ml WRE) (p < 0.001). Oxidant scavenging activity was increased by WRE (0.05-0.4 mg/ml, p < 0.0001). PBMC TNF-α and IL-10 levels were decreased by 0.2-0.4 mg/ml WRE, whereas IL-1ß levels were increased by 0.05-0.4 mg/ml WRE (p < 0.0001). In THP-1 cells, WRE (0.05-0.4 mg/ml) decreased TNF-α, IL-1ß and IL-6 levels (p < 0.0001). At 24 h, GSH levels were decreased in PBMC's, whilst increased in THP-1 cells by 0.2-0.4 mg/ml WRE (p < 0.0001). At 72 h, WRE (0.1-0.4 mg/ml) decreased GSH levels in both cell lines (p < 0.0001). At 24 h, WRE (0.2-0.4 mg/ml) increased PBMC caspase (-8, -3/7) activities whereas WRE (0.05, 0.1, 0.4 mg/ml) increased THP-1 caspase (-9, -3/7) activities (p < 0.0001). At 72 h, PBMC caspase (-8, -9, -3/7) activities were increased at 0.05-0.1 mg/ml WRE (p < 0.0001). In THP-1 cells, caspase (-8, -9, -3/7) activities and ATP levels were increased by 0.1-0.2 mg/ml WRE, whereas decreased by 0.05 and 0.4 mg/ml WRE (72 h, p < 0.0001). CONCLUSION: In PBMC's and THP-1 cells, WRE proved to effectively modulate antioxidant activity, inflammatory cytokines and cell death. In THP-1 cells, WRE decreased pro-inflammatory cytokine levels, which may alleviate cancer cachexia and excessive leukaemic cell growth.

Consumption of processed food dietary patterns in four African populations.

OBJECTIVE: To identify predominant dietary patterns in four African populations and examine their association with obesity. DESIGN: Cross-sectional study.Setting/SubjectsWe used data from the Africa/Harvard School of Public Health Partnership for Cohort Research and Training (PaCT) pilot study established to investigate the feasibility of a multi-country longitudinal study of non-communicable chronic disease in sub-Saharan Africa. We applied principal component analysis to dietary intake data collected from an FFQ developed for PaCT to ascertain dietary patterns in Tanzania, South Africa, and peri-urban and rural Uganda. The sample consisted of 444 women and 294 men. RESULTS: We identified two dietary patterns: the Mixed Diet pattern characterized by high intakes of unprocessed foods such as vegetables and fresh fish, but also cold cuts and refined grains; and the Processed Diet pattern characterized by high intakes of salad dressing, cold cuts and sweets. Women in the highest tertile of the Processed Diet pattern score were 3·00 times more likely to be overweight (95 % CI 1·66, 5·45; prevalence=74 %) and 4·24 times more likely to be obese (95 % CI 2·23, 8·05; prevalence=44 %) than women in this pattern's lowest tertile (both P<0·0001; prevalence=47 and 14 %, respectively). We found similarly strong associations in men. There was no association between the Mixed Diet pattern and overweight or obesity. CONCLUSIONS: We identified two major dietary patterns in several African populations, a Mixed Diet pattern and a Processed Diet pattern. The Processed Diet pattern was associated with obesity.