Poor oral health and the risk of esophageal squamous cell carcinoma in Malawi.

Esophageal squamous cell carcinoma (ESCC) is the second most common cancer in Malawi. Risk factors for this cancer in Malawi are poorly understood. Poor oral health has previously been linked to increased ESCC risk in other high-incidence regions, including parts of Eastern and Southern Africa. We assessed the relationship between oral health and ESCC risk in a sex, age and location frequency-matched case-control study based at two hospitals in Lilongwe, Malawi from 2017 to 2020. Trained interviewers used a structured questionnaire and direct observation to collect data on demographics; behaviors; oral hygiene habits; the sum of decayed, missing or filled teeth (DMFT score); oral mucosa status; lip depigmentation and dental fluorosis via a visual scale. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI), adjusted for known and suspected ESCC risk factors. During the study period, 300 cases and 300 controls were enrolled. Subjects in the highest tertile of DMFT score (≥7) had an increased risk of ESCC with an adjusted OR of 1.96 (95% CI: 1.16-3.36) compared to those with a DMFT score of 0. Severe dental fluorosis was associated with a statistically nonsignificant increased risk of ESCC (adjusted OR = 2.24, 95% CI: 0.97-5.49) compared to individuals with no fluorosis. Associations with oral mucosa status, lip depigmentation and toothbrushing method and frequency were mostly null or uncertain. Poor oral health, indicated by a higher DMFT score, was associated with increased ESCC risk in Malawi. Dental fluorosis is another possible risk factor in this population, but further evaluation is necessary to clarify any effects of fluorosis on ESCC risk.

State of the science and future directions for research on HIV and cancer: Summary of a joint workshop sponsored by IARC and NCI.

An estimated 38 million people live with human immunodeficiency virus (HIV) worldwide and are at excess risk for multiple cancer types. Elevated cancer risks in people living with HIV (PLWH) are driven primarily by increased exposure to carcinogens, most notably oncogenic viruses acquired through shared transmission routes, plus acceleration of viral carcinogenesis by HIV-related immunosuppression. In the era of widespread antiretroviral therapy (ART), life expectancy of PLWH has increased, with cancer now a leading cause of co-morbidity and death. Furthermore, the types of cancers occurring among PLWH are shifting over time and vary in their relative burden in different parts of the world. In this context, the International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) convened a meeting in September 2022 of multinational and multidisciplinary experts to focus on cancer in PLWH. This report summarizes the proceedings, including a review of the state of the science of cancer descriptive epidemiology, etiology, molecular tumor characterization, primary and secondary prevention, treatment disparities and survival in PLWH around the world. A consensus of key research priorities and recommendations in these domains is also presented.

HIV and prior exposure to antiretroviral therapy alter tumour composition and tumour: T-cell associations in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of lymphoma worldwide, accounting for up to 40% of new non-Hodgkin Lymphoma (NHL) globally. People living with HIV are up to 17 times more likely to develop NHL, and as such, DLBCL is the leading cause of cancer death in this high-risk population. While histologically indistinguishable, HIV-associated (HIV+) and HIV-negative (HIV-) DLBCL are molecularly distinct, and biological differences may have implications for the development of future therapeutic interventions. Further, the impact of immunologic differences in people with HIV, including preceding ART, remains largely unknown. Here, we investigate the impact of HIV infection and ART exposure on the clinical features of DLBCL and T-cell immune response by performing imaging mass cytometry on our unique patient cohort in Malawi. In this cohort, HIV infection is positively prognostic, and HIV+/ART-naïve patients have the best outcomes. No established biomarkers other than Ki67 are associated with HIV or ART status, and the only tumour-intrinsic biomarkers that remain prognostic are MYC and MYC/BCL2 protein co-expression. Finally, TCR clonality is associated with distinct tumour-T cell interactions by HIV/ART status, indicating differential anti-tumour immune responses. We demonstrate previously undescribed HIV and ART-related differences in the DLBCL tumour microenvironment.

Global oncology research and training at US National Cancer Institute-designated cancer centres: results of the 2021 Global Oncology Survey.

Global oncology research and training are crucial to address the growing global burden of cancer, which largely and increasingly occurs in low-income and middle-income countries. To better understand global oncology activities at the 71 National Cancer Institute (NCI)-designated cancer centres, the US NCI Centre for Global Health regularly surveys cancer centre directors, global oncology leads, and principal investigators in 36 US states and the District of Columbia. The survey results complement internal and publicly available data about global oncology research funded directly by the US National Institutes of Health to provide a comprehensive catalogue of global oncology research, training, and activities led by NCI-designated cancer centres. 91% (61 of 67) of responding cancer centres reported global oncology activities not directly funded by the National Institutes of Health. The survey results indicate that global oncology is an important priority at cancer centres and provide a valuable resource for these centres, researchers, collaborators, trainees, and the NCI and other funders.

Global Cancer Surgery: pragmatic solutions to improve cancer surgery outcomes worldwide.

The first Lancet Oncology Commission on Global Cancer Surgery was published in 2015 and serves as a landmark paper in the field of cancer surgery. The Commission highlighted the burden of cancer and the importance of cancer surgery, while documenting the many inadequacies in the ability to deliver safe, timely, and affordable cancer surgical care. This Commission builds on the first Commission by focusing on solutions and actions to improve access to cancer surgery globally, developed by drawing upon the expertise from cancer surgery leaders across the world. We present solution frameworks in nine domains that can improve access to cancer surgery. These nine domains were refined to identify solutions specific to the six WHO regions. On the basis of these solutions, we developed eight actions to propel essential improvements in the global capacity for cancer surgery. Our initiatives are broad in scope, pragmatic, affordable, and contextually applicable, and aimed at cancer surgeons as well as leaders, administrators, elected officials, and health policy advocates. We envision that the solutions and actions contained within the Commission will address inequities and promote safe, timely, and affordable cancer surgery for every patient, regardless of their socioeconomic status or geographic location.

An international report on bacterial communities in esophageal squamous cell carcinoma.

The incidence of esophageal squamous cell carcinoma (ESCC) is disproportionately high in the eastern corridor of Africa and parts of Asia. Emerging research has identified a potential association between poor oral health and ESCC. One possible link between poor oral health and ESCC involves the alteration of the microbiome. We performed an integrated analysis of four independent sequencing efforts of ESCC tumors from patients from high- and low-incidence regions of the world. Using whole genome sequencing (WGS) and RNA sequencing (RNAseq) of ESCC tumors from 61 patients in Tanzania, we identified a community of bacteria, including members of the genera Fusobacterium, Selenomonas, Prevotella, Streptococcus, Porphyromonas, Veillonella and Campylobacter, present at high abundance in ESCC tumors. We then characterized the microbiome of 238 ESCC tumor specimens collected in two additional independent sequencing efforts consisting of patients from other high-ESCC incidence regions (Tanzania, Malawi, Kenya, Iran, China). This analysis revealed similar ESCC-associated bacterial communities in these cancers. Because these genera are traditionally considered members of the oral microbiota, we next explored whether there was a relationship between the synchronous saliva and tumor microbiomes of ESCC patients in Tanzania. Comparative analyses revealed that paired saliva and tumor microbiomes were significantly similar with a specific enrichment of Fusobacterium and Prevotella in the tumor microbiome. Together, these data indicate that cancer-associated oral bacteria are associated with ESCC tumors at the time of diagnosis and support a model in which oral bacteria are present in high abundance in both saliva and tumors of some ESCC patients.

Prevalence of traditional, complementary, and alternative medicine (TCAM) among adult cancer patients in Malawi.

PURPOSE: The objective of this study is to document the prevalence of traditional, complementary, and alternative medicine (TCAM) use by adult cancer patients at a national teaching hospital in Malawi. We aim to document the products/therapies used, the reason for use, as well as patient-reported satisfaction with TCAM practitioners and modalities. METHODS: We conducted investigator-administered interviews with adult cancer patients presenting to the Kamuzu Central Hospital (KCH) Cancer Clinic in Lilongwe, Malawi between January and July 2018. The KCH is a national teaching hospital in the capital of Lilongwe, which serves patients with cancer from the northern half of Malawi. Descriptive statistics were used to describe TCAM use and logistic regression was applied to identify predictors of TCAM. RESULTS: A total of 263 participants completed the survey, of which 70% (n = 183) were female and average age was 45 (SD 14) years old. The prevalence of overall TCAM use was 84% (n = 222), and 60% (n = 157) of participants reported combining TCAM with conventional cancer treatment. The majority of patients used TCAM to directly treat their cancer versus for symptom management. Patients reported using faith-based healing (64%, n = 168), herbal medicine (56%, n = 148), diet change (46%, n = 120), and vitamins/minerals (23%, n = 61). Participants reported the highest satisfaction for physicians among practitioners and diet change for modalities. Female gender was found to be a predictor of TCAM with conventional treatment use, no other significant predictors were observed. CONCLUSION: There is a high prevalence of TCAM use among an adult population with cancer in Malawi, and a wide variety in the TCAM modalities used among patients. Additional studies are needed to identify risks and benefits of TCAM use to assist with policy and public health, patient safety, and holistically address the global burden of cancer.

Spatial distribution of incident pediatric Burkitt lymphoma in central and northern Malawi and association with malaria prevalence.

BACKGROUND: Burkitt lymphoma (BL) accounts for 90% of pediatric lymphomas in sub-Saharan Africa. Plasmodium falciparum malaria is considered an etiological factor of BL. We describe the geographic distribution of pediatric BL in Malawi and association with P. falciparum malaria prevalence rate (PfPR). METHODS: We enrolled 220 pathologically confirmed incident pediatric BL cases (2013-2018) into an observational clinical cohort at Kamuzu Central Hospital (KCH) in Lilongwe district. KCH is the main tertiary cancer referral center serving the central and northern regions of Malawi. Using an ecological study design, we calculated district-level annual BL incidence rate using census population estimates. District-level PfPR was extracted from the National Malaria Control Program 2010 report. BL incidence and PfPR maps were constructed in QGIS. Moran's I  test was used to identify BL spatial clusters. Pearson's correlation and multiple linear regression analyses were used to statistically examine the relationship between PfPR and BL. RESULTS: BL incidence was higher in central region districts (8.2 cases per million) than northern districts (2.9 cases per million) and was elevated in lakeshore districts. Districts with elevated PfPR tended to have elevated BL incidence. A low-risk BL cluster was detected in the north. Statistically, BL incidence was positively correlated with PfPR (r = .77, p < .01). A 1% increase in PfPR predicted an increase in BL incidence of 0.2 cases per million (p = .03), when controlling for travel time from referral district hospital to KCH. CONCLUSION: Our study supports evidence for an association between P. falciparum and BL and highlights a need to improve geographic accessibility to tertiary cancer services in Malawi's northern region.

The International Collaboration for Research methods Development in Oncology (CReDO) workshops: shaping the future of global oncology research.

Low-income and middle-income countries (LMICs) have a disproportionately high burden of cancer and cancer mortality. The unique barriers to optimum cancer care in these regions necessitate context-specific research. The conduct of research in LMICs has several challenges, not least of which is a paucity of formal training in research methods. Building capacity by training early career researchers is essential to improve research output and cancer outcomes in LMICs. The International Collaboration for Research methods Development in Oncology (CReDO) workshop is an initiative by the Tata Memorial Centre and the National Cancer Grid of India to address gaps in research training and increase capacity in oncology research. Since 2015, there have been five CReDO workshops, which have trained more than 250 oncologists from India and other countries in clinical research methods and protocol development. Participants from all oncology and allied fields were represented at these workshops. Protocols developed included clinical trials, comparative effectiveness studies, health services research, and observational studies, and many of these protocols were particularly relevant to cancer management in LMICs. A follow-up of these participants in 2020 elicited an 88% response rate and showed that 42% of participants had made progress with their CReDO protocols, and 73% had initiated other research protocols and published papers. In this Policy Review, we describe the challenges to research in LMICs, as well as the evolution, structure, and impact of CReDO and other similar workshops on global oncology research.

Uptake and safety of community-based "screen-and-treat" with thermal ablation preventive therapy for cervical cancer prevention in rural Lilongwe, Malawi.

Malawi has the highest invasive cervical cancer (ICC) mortality rate worldwide, and ICC is the leading cause of cancer death among women. In 2004, Malawi adopted visual inspection with acetic acid (VIA) and ablative treatment with cryotherapy. However, screening coverage has remained low (<30%) and few women (<50%) who require ablative treatment receive it. Additional barriers include long distances to health facilities and challenges with maintaining gas supplies. Thermal ablation is a safe and effective alternative to cryotherapy. We assessed the safety and uptake of community-based ICC screening with VIA and same-day treatment using a handheld thermocoagulator (HTU) in rural Malawi. We held educational talks alongside community leaders and conducted VIA screening in nonclinic community settings to nonpregnant women aged 25 to 49 years without history of hysterectomy or genital cancer/precancer. Eligible women received same-day thermal ablation and HIV testing/counseling. We collected cervical biopsies before treatment and followed up women at Weeks 6 and 12, with repeat biopsy at Week 12. Between July and August 2017, 408 (88%) of 463 eligible women underwent VIA. Overall, 7% (n = 30) of women had a positive VIA, of whom 93% (n = 28) underwent same-day thermal ablation. Among the 30 VIA-positive women, 5 had cervical intraepithelial neoplasia (CIN) 1, 4 had CIN 2/3 and 21 had benign histologic findings. Abnormal vaginal discharge (60%) and light vaginal bleeding (52%) were the most reported adverse events. There was high uptake of the community-based ICC screening in the study population and treatment was safe in this setting. Similar strategies that minimize false-positive results are urgently needed in Malawi.

Pediatric lymphoma patients in Malawi present with poor health-related quality of life at diagnosis and improve throughout treatment and follow-up across all Pediatric PROMIS-25 domains.

BACKGROUND: Patient-reportedoutcomes (PROs) that assess health-related quality of life (HRQoL) are increasingly important components of cancer care and research that are infrequently used in sub-Saharan Africa (SSA). METHODS: We administered the Chichewa Pediatric Patient-Reported Outcome Measurement Information System Pediatric (PROMIS)-25 at diagnosis, active treatment, and follow-up among pediatric lymphoma patients in Lilongwe, Malawi. Mean scores were calculated for the six PROMIS-25 HRQoL domains (Mobility, Anxiety, Depressive Symptoms, Fatigue, Peer Relationships, Pain Interference). Differences in HRQoL throughout treatment were compared using the minimally important difference (MID) and an ANOVA analysis. Kaplan-Meier survival estimates and Cox hazard ratios for mortality are reported. RESULTS: Seventy-five children completed PROMIS-25 surveys at diagnosis, 35 (47%) during active treatment, and 24 (32%) at follow-up. The majority of patients died (n = 37, 49%) or were lost to follow-up (n = 6, 8%). Most (n = 51, 68%) were male, median age was 10 (interquartile range [IQR] 8-12), 48/73 (66%) presented with advanced stage III/IV, 61 (81%) were diagnosed with Burkitt lymphoma and 14 (19%) Hodgkin lymphoma. At diagnosis, HRQoL was poor across all domains, except for Peer Relationships. Improvements in HRQoL during active treatment and follow-up exceeded the MID. On exploratory analysis, fair-poor PROMIS Mobility <40 and severe Pain Intensity = 10 at diagnosis were associated with increased mortality risk and worse survival, but were not statistically significant. CONCLUSIONS: Pediatric lymphoma patients in Malawi present with poor HRQoL that improves throughout treatment and survivorship. Baseline PROMIS scores may provide important prognostic information. PROs offer an opportunity to include patient voices and prioritize holistic patient-centered care in low-resource settings.

Building Capacity for Global Cancer Research: Existing Opportunities and Future Directions.

Cancer incidence and mortality are increasing in low- and middle-income countries (LMICs), where more than 75% of global cancer burden will occur by the year 2040. The primary drivers of cancer morbidity and mortality in LMICs are environmental and behavioral risk factors, inadequate prevention and early detection services, presence of comorbidities, and poor access to treatment and palliation. These same drivers also contribute to marked cancer health disparities in high-income countries. Studying cancer in LMICs provides opportunities to better understand and address these drivers to benefit populations worldwide, and reflecting this, global oncology as an academic discipline has grown substantially in recent years. However, sustaining this growth requires a uniquely trained workforce with the skills to pursue relevant, rigorous, and equitable global oncology research. Despite this need, dedicated global cancer research training programs remain somewhat nascent and uncoordinated. In this paper, we discuss efforts to address these gaps in global cancer research training at the US National Institutes of Health.

Identifying transcriptional profiles and evaluating prognostic biomarkers of HIV-associated diffuse large B-cell lymphoma from Malawi.

Lymphoma incidence in sub-Saharan Africa (SSA) is increasing due to HIV and population aging. Diffuse Large B-cell lymphoma (DLBCL), the most common lymphoma in SSA and worldwide, is highly associated with HIV, but molecular studies of HIV-associated DLBCL are scarce globally. We describe profiling of DLBCL from Malawi, aiming to elucidate tumor biology and identify clinically meaningful biomarkers specifically for SSA. Between June 1, 2013 and June 1, 2016, 59 cases of DLBCL (32 HIV+/27 HIV-) enrolled in the Kamuzu Central Hospital Lymphoma Study were characterized, of which 54 (92%) were negative for Epstein-Barr virus. Gene expression profiling (GEP) by whole transcriptome sequencing was performed on the first 36 cases (22 HIV+/14 HIV-). Immunohistochemistry (IHC) and GEP results were compared with published data and correlated to clinical outcome and pathologic features. Unsupervised clustering strongly segregated DLBCL by HIV status (p = 0.0003, Chi-squared test), indicating a marked contribution of HIV to expression phenotype. Pathway analysis identified that HIV-associated tumors were enriched in hypoxia, oxidative stress, and metabolism related gene expression patterns. Cell-of-origin subtype, determined by sequencing and IHC, did not associate with differences in overall survival (OS), while Ki-67 proliferation index ≥80% was associated with inferior OS in HIV+ DLBCL only (p = 0.03) and cMYC/BCL2 co-expression by IHC was negatively prognostic across the entire cohort (p = 0.01). This study provides among the first molecular characterizations of DLBCL from SSA, demonstrates marked gene expression differences by HIV status, and identifies genomic and immunophenotypic characteristics that can inform future basic and clinical investigations.

Outcomes and prognostic factors for women with breast cancer in Malawi.

BACKGROUND: Breast cancer incidence in sub-Saharan Africa (SSA) is increasing, and SSA has the highest age-standardized breast cancer mortality rate worldwide. However, high-quality breast cancer data are limited in SSA. MATERIALS AND METHODS: We examined breast cancer patient and tumor characteristics among women in Lilongwe, Malawi and evaluated risk factor associations with patient outcomes. We consecutively enrolled 100 women ≥ 18 years with newly diagnosed, pathologically confirmed breast cancer into a prospective longitudinal cohort with systematically assessed demographic data, HIV status, and clinical characteristics. Tumor subtypes were further determined by immunohistochemistry, overall survival (OS) was estimated using Kaplan-Meier methods, and hazards ratios (HR) were calculated by Cox proportional hazard analyses. RESULTS: Of the 100 participants, median age was 49 years, 19 were HIV-positive, and 75 presented with late stage (III/IV) disease. HER2-enriched and triple-negative/basal-like subtypes represented 17% and 25% tumors, respectively. One-year OS for the cohort was 74% (95% CI 62-83%). Multivariable analyses revealed mortality was associated with HIV (HR, 5.15; 95% CI 1.58-16.76; p = 0.006), stage IV disease (HR, 8.86; 95% CI 1.07-73.25; p = 0.043), and HER2-enriched (HR, 7.46; 95% CI 1.21-46.07; p = 0.031), and triple-negative subtypes (HR, 7.80; 95% CI 1.39-43.69; p = 0.020). CONCLUSION: Late stage presentation, HER2-enriched and triple-negative subtypes, and HIV coinfection were overrepresented in our cohort relative to resource-rich settings and were associated with mortality. These findings highlight robust opportunities for population- and patient-level interventions across the entire cascade of care to improve breast cancer outcomes in low-income countries in SSA.

How I treat Burkitt lymphoma in children, adolescents, and young adults in sub-Saharan Africa.

Burkitt lymphoma (BL) is the most common pediatric cancer in sub-Saharan Africa (SSA), and also occurs frequently among adolescents and young adults (AYAs), often associated with HIV. Treating BL in SSA poses particular challenges. Although highly effective, high-intensity cytotoxic treatments used in resource-rich settings are usually not feasible, and lower-intensity continuous infusion approaches are impractical. In this article, based on evidence from the region, we review management strategies for SSA focused on diagnosis and use of prephase and definitive treatment. Additionally, potentially better approaches for risk stratification and individualized therapy are elaborated. Compared with historical very low-intensity approaches, the relative safety, feasibility, and outcomes of regimens incorporating anthracyclines and/or high-dose systemic methotrexate for this population are discussed, along with requirements to administer such regimens safely. Finally, research priorities for BL in SSA are outlined including novel therapies, to reduce the unacceptable gap in outcomes for patients in SSA vs high-income countries (HICs). Sustained commitment to incremental advances and innovation, as in cooperative pediatric oncology groups in HICs, is required to transform care and outcomes for BL in SSA through international collaboration.

High Cancer Burden Among Antiretroviral Therapy Users in Malawi: A Record Linkage Study of Observational Human Immunodeficiency Virus Cohorts and Cancer Registry Data.

BACKGROUND: With antiretroviral therapy (ART), AIDS-defining cancer incidence has declined and non-AIDS-defining cancers (NADCs) are now more frequent among human immunodeficiency virus (HIV)-infected populations in high-income countries. In sub-Saharan Africa, limited epidemiological data describe cancer burden among ART users. METHODS: We used probabilistic algorithms to link cases from the population-based cancer registry with electronic medical records supporting ART delivery in Malawi's 2 largest HIV cohorts from 2000-2010. Age-adjusted cancer incidence rates (IRs) and 95% confidence intervals were estimated by cancer site, early vs late incidence periods (4-24 and >24 months after ART start), and World Health Organization (WHO) stage among naive ART initiators enrolled for at least 90 days. RESULTS: We identified 4346 cancers among 28 576 persons. Most people initiated ART at advanced WHO stages 3 or 4 (60%); 12% of patients had prevalent malignancies at ART initiation, which were predominantly AIDS-defining eligibility criteria for initiating ART. Kaposi sarcoma (KS) had the highest IR (634.7 per 100 000 person-years) followed by cervical cancer (36.6). KS incidence was highest during the early period 4-24 months after ART initiation. NADCs accounted for 6% of new cancers. CONCLUSIONS: Under historical ART guidelines, NADCs were observed at low rates and were eclipsed by high KS and cervical cancer burden. Cancer burden among Malawian ART users does not yet mirror that in high-income countries. Integrated cancer screening and management in HIV clinics, especially for KS and cervical cancer, remain important priorities in the current Malawi context.

Mature outcomes and prognostic indices in diffuse large B-cell lymphoma in Malawi: a prospective cohort.

Outcomes for diffuse large B-cell lymphoma (DLBCL) in sub-Saharan Africa (SSA) are poorly described. We report mature data from one of the first prospective SSA cohorts. Patients aged ≥18 years with DLBCL were enrolled in Malawi 2013-2017. Participants were treated with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy and concurrent antiretroviral therapy (ART) if positive for human immunodeficiency virus (HIV+). Eighty-six participants (mean age 47 years, standard deviation 13) were enrolled: 54 (63%) were male and 51 (59%) were HIV+, of whom 34 (67%) were on ART at DLBCL diagnosis. Median CD4 count was 0·113 cells × 109 /l (interquartile range [IQR] 0·062-0·227) and 25 (49%) had HIV viral load <400 copies/µl. Participants received median six cycles CHOP (IQR 4-6). No patients were lost to follow-up and the 2-year overall survival was 38% (95% confidence interval 28-49). In multivariable analyses, Eastern Cooperative Oncology Group performance status (PS) ≥2 and lactate dehydrogenase (LDH) >2× upper limit of normal (ULN) were associated with mortality. HIV status was not associated with mortality. A simplified prognostic model of LDH >2× ULN and PS ≥2 performed at least as well as the age-adjusted International Prognostic Index. DLBCL can be successfully treated in SSA and outcomes did not differ by HIV status. A simplified prognostic model prognosticates well and may be easier to use in resource-limited settings but requires validation.

Real-world experience using hydroxyurea in children with sickle cell disease in Lilongwe, Malawi.

INTRODUCTION: Sickle cell disease (SCD) is among the most common inherited hematologic diseases in sub-Saharan Africa (SSA). Historically, hydroxyurea administration in SSA has been restricted due to limited region-specific evidence for safety and efficacy. METHODS: We conducted a prospective observational cohort study of pediatric patients with SCD in Malawi. From January 2015 to November 2017, hydroxyurea at doses of 10-20 mg/kg/day was administered to children with clinically severe disease (targeted use policy). From December 2017 to July 2018, hydroxyurea was prescribed to all patients (universal use policy). RESULTS: Of 187 patients with SCD, seven (3.7%) died and 23 (12.3%) were lost to follow-up. The majority (135, 72.2%) were prescribed hydroxyurea, 59 (43.7%) under the targeted use policy and 76 (56.3%) under the universal use policy. There were no documented severe toxicities. Under the targeted use policy, children with SCD demonstrated absolute decreases in the rates of hospitalization (-4.1 per 1000 person-days; -7.2, -1.0; P = .004), fevers (-4.2 per 1000 person-days; -7.2, -1.1; P = .002), transfusions (-2.3 per 1000 person-days; 95% confidence interval: -4.9, 0.3; P = .06), and annual school absenteeism (-51.2 per person-year; -60.1, -42.3; P < .0001) within 6 months of hydroxyurea commencement. CONCLUSION: We successfully implemented universal administration of hydroxyurea to children with SCD at a tertiary hospital in Malawi. Similar to recently reported trials, hydroxyurea was safe and effective during routine programmatic experience, with clinical benefits particularly among high-risk children. This highlights the importance of continued widespread scale-up of hydroxyurea within SCD programs across SSA.

Epidemiological and histopathological profile of malignant melanoma in Malawi.

BACKGROUND: Studies on malignant melanoma have largely focused on Caucasian populations due to higher incidence in lighter-skinned individuals. While there is a well developed body of literature describing melanoma in African-Americans, much less is known about melanoma in black Africans. Prior reports have suggested that it is reportedly extremely rare in black Africans who are considered to mostly have the acral lentiginous subtype. However, an accurate understanding of melanoma in this part of the world is hindered by the very limited nature of prior publications. The aim of this study was to determine the epidemiological profile, anatomical distribution and histopathological features of melanoma presenting in Africans at a tertiary referral hospital in Malawi. METHODS: This is a retrospective study that characterized melanoma cases diagnosed from January 2012 to December 2017, at a cancer referral centre in Malawi. All confirmed, malignant melanoma cases during the study period were retrieved. Data abstracted included age, sex, anatomic site and whether it was a primary or metastatic site. Breslow thickness in millimetres, Clark level of invasion, presence of ulceration and melanoma subtype were also evaluated. RESULTS: One hundred thirty-two cases were included in the study, 81 (61%) were female and 26 (20%) were from a metastatic site. The mean age was 57 years (sd = 15) with the majority in the age group 60-69 years. Males presented at an older age than females. Ninety five percent of cutaneous melanomas were located on acral sites, most commonly the foot (87%) and the most common histopathological subtype was acral lentiginous. Eighty four percent presented with a Breslow thickness over 4 mm (median 9 mm). CONCLUSION: Our study shows that malignant melanoma occurs in black people in Malawi and may be an under-appreciated malignancy. While long term clinical follow-up was not available, most patients presented at late stages of the disease, supporting a poor prognosis. These results suggest that increased awareness of melanoma in black Africans and earlier intervention may have meaningful impacts on outcomes and survival.