Objective HIV infection is associated with cancer risk. This relationship has resulted in a growing cancer burden, especially in resource-limited countries where HIV is highly prevalent. Little is known, however, about how HIV affects cancer survival in these settings. We therefore investigated the role of HIV in cancer survival in Uganda. Design Retrospective cohort (N = 802). Methods Eligible cancer patients were residents of Kyadondo County, at least 18 years of age at cancer diagnosis, and diagnosed between 2003 and 2010 with one of the following: breast cancer, cervical cancer, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, or esophageal cancer. Patients were classified as HIV-infected at cancer diagnosis based on a documented positive HIV antibody test, medical history indicating HIV infection, or an HIV clinic referral letter. The primary outcome, vital status at 1 year following cancer diagnosis, was abstracted from the medical record or determined through linkage to the national hospice database. The risk of death during the year after cancer diagnosis was compared between cancer patients with and without evidence of HIV infection using Cox proportional hazards regression. Results HIV-infected cancer patients in Uganda experienced a more than two-fold increased risk of death during the year following cancer diagnosis compared to HIV-uninfected cancer patients [hazard ratio 2.28; 95% confidence interval (CI) 1.61–3.23]. This association between HIV and 1-year cancer survival was observed for both cancers with (hazard ratio 1.56; 95% CI 1.04–2.34) and without (hazard ratio 2.68; 95% CI 1.20–5.99) an infectious cause. Conclusion This study demonstrates the role of HIV in cancer survival for both cancers with and without an infectious cause in a resource-limited, HIV-endemic setting.

Background Sub-Saharan Africa suffers from a dual burden of infectious and non-communicable diseases. There is limited data on causes and trends of admission and death among patients on the medical wards. Understanding the major drivers of morbidity and mortality would help inform health systems improvements. We determined the causes and trends of admission and mortality among patients admitted to Mulago Hospital, Kampala, Uganda. Methods and results The medical record data base of patients admitted to Mulago Hospital adult medical wards from January 2011 to December 2014 were queried. A detailed history, physical examination and investigations were completed to confirm the diagnosis and identify comorbidities. Any histopathologic diagnoses were made by hematoxylin and eosin tissue staining. We identified the 10 commonest causes of hospitalization, and used Poisson regression to generate annual percentage change to describe the trends in causes of hospitalization. Survival was calculated from the date of admission to the date of death or date of discharge. Cox survival analysis was used to identify factors associate with in-hospital mortality. We used a statistical significance level of p<0.05. A total of 50,624 patients were hospitalized with a median age of 38 (range 13–122) years and 51.7% females. Majority of patients (72%) had an NCD condition as the primary reason for admission. Specific leading causes of morbidity were HIV/AIDS in 30% patients, hypertension in 14%, tuberculosis (TB) in 12%), non-TB pneumonia in11%) and heart failure in 9.3%. There was decline in the proportion of hospitalization due to malaria, TB and pneumonia with an annual percentage change (apc) of -20% to -6% (all p<0.03) with an increase in proportions of admissions due to chronic kidney disease, hypertension, stroke and cancer, with apc 13.4% to 24%(p<0.001). Overall, 8,637(17.1%) died during hospitalization with the highest case fatality rates from non-TB pneumonia (28.8%), TB (27.1%), stroke (26.8%), cancer (26.1%) and HIV/AIDS (25%). HIV-status, age above 50yrs and being male were associated with increased risk of death among patients with infections. Conclusion Admissions and case fatality rates for both infectious and non-infectious diseases were high, with declining trends in infectious diseases and a rising trend in NCDs. Health care systems in sub-Saharan region need to prepare to deal with dual burden of disease.

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Background The introduction of antiretroviral therapy (ART) in the US and Europe has led to changes in the incidence of cancers among HIV- infected persons, including dramatic decreases in Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL), and increases in Hodgkin lymphoma (HD), liver and anogenital malignancies. We sought to evaluate whether increasing availability of ART is associated with changing cancer incidence in Uganda. Methods Incident cases of 10 malignancies were identified from Kampala Cancer Registry from 1999 to 2008. ART coverage rates for Uganda were abstracted from UNAIDS reports. Negative binomial and poisson regression modeled the association between ART coverage and age-adjusted cancer incidence. Results ART coverage in Uganda increased from 0 to 43% from 1999 to 2008. With each 10% increase in ART coverage, incidence of Kaposi sarcoma decreased by 5%(incidence rate ratio [IRR]=0·95, 95% CI: 0·91–0·99, P=0·02) and stomach cancer decreased by 13% (IRR=0·87 [0·80–0·95], P=0·002). Conversely, incidence of non-Hodgkin lymphoma increased by 6% (IRR=1·06 [1–1·12], P=0·05), liver cancer by 12% (IRR=1·12 [1·04–1·21], P=0·002), prostate cancer by 5% (IRR=1·05 [1–1·10], P=0·05), and breast cancer by 5% (IRR=1·05 [1–1·11], P=0·05). ART coverage was not associated with incidence of invasive cervical cancer, lung, colon, and Hodgkin disease. These findings were similar when restricted to histologically confirmed cases. Conclusion Our findings suggest that AIDS-defining malignancies and other malignancies are likely to remain significant public health burdens in sub-Saharan Africa even as ART availability increases.

Burkitt lymphoma (BL) accounts for the majority of pediatric non-Hodgkin lymphomas being less common but significantly more lethal when diagnosed in adults. Much of our knowledge of the genetics of BL thus far has originated from the study of pediatric BL (pBL), leaving its relationship to adult (aBL) and other adult lymphomas not fully explored. We sought to more thoroughly identify the somatic changes that underlie lymphomagenesis in aBL and any molecular features that associate with clinical disparities within and between pBL and aBL. Through comprehensive whole-genome sequencing of 230 BL and 295 diffuse large B-cell lymphoma (DLBCL) tumors, we identified additional significantly mutated genes (SMGs) including more genetic features that associate with tumor EBV status, and unraveled new distinct subgroupings within BL and DLBCL with three predominantly comprising BLs: DGG-BL (DDX3X, GNA13 and GNAI2), IC-BL (ID3, CCND3), and Q53-BL (quiet TP53). Each BL subgroup is characterized by combinations of common driver and non-coding mutations caused by aberrant somatic hypermutation (aSHM). The largest subgroups of BL cases, IC-BL and DGG-BL are further characterized by distinct biological and gene expression differences. IC-BL and DGG-BL and their prototypical genetic features (ID3 and TP53) had significant associations with patient outcomes that were different among aBL and pBL cohorts. These findings highlight shared pathogenesis between aBL and pBL, and establish genetic subtypes within BL that serve to delineate tumors with distinct molecular features, providing a new framework for epidemiological, diagnostic, and therapeutic strategies.

Introduction . Limited data suggest that children with cancer in sub-Saharan Africa have poor survival. We aimed to describe the presentation, treatment outcomes, and factors associated with survival among children with cancer managed at Uganda Cancer Institute. Methods . We retrospectively evaluated patients with childhood cancer (age ≤19 years) from Kyadondo County treated at Uganda Cancer Institute from 2006 to 2009. Cox’s regression and Kaplan-Meier methods were used to study 1-year survival. Results . Among 310 patients studied, median age was 7 years (range = 0.25-19 years), 64% were boys, and 92% had histological confirmation of cancer diagnosis. The commonest diagnoses were Burkitt lymphoma (BL, N = 87), Kaposi sarcoma (KS, N = 68), non-BL non-Hodgkin lymphoma (NHL, N = 32), acute lymphoblastic leukemia (ALL, N = 28), Wilms (N = 28), and Hodgkin disease (HD, N = 20). Advanced disease at diagnosis was common for all cancers (ranging from 45% for KS to 83% for non-BL NHL). Overall, 33.2% abandoned treatment. One-year survival was 68% for HD (95% confidence interval [CI] = 11.3-40.6), 67% for KS (95% CI = 52.1-77.9), 55% for BL (95% CI = 42-66.9), 44% for Wilms (95% CI = 22.5-63), 43% for non-BL NHL (95% CI = 23.3-61.3), and 20% for ALL (95% CI = 6.4-38.7). In univariate and multivariate analysis, anemia and thrombocytopenia were associated with mortality for several cancers. Conclusion . Survival among children with cancer in Uganda is poor. Advanced stage disease and loss to follow-up likely contribute to poor outcomes. Anemia and thrombocytopenia may augment traditional staging methods to provide better prognostic factors in Uganda and warrant further evaluation.

Purpose “Endemic” Burkitt lymphoma (BL) is a common childhood cancer in Africa. Social and treatment factors may contribute to poor survival. With the aim of improving BL outcomes in Uganda, we undertook a comprehensive project (BL Project) that provided diagnostic support, access to standard chemotherapy, nutritional evaluations, and case management. We evaluated survival of children with BL in the context of the project. Patients and methods Patients followed by the BL Project who consented to research were enrolled in this study. Children with a pathology diagnosis consistent with BL were eligible. Data were collected prospectively. First‐line chemotherapy generally consisted of six cycles of cyclophosphamide, vincristine, low‐dose methotrexate (COM). We used Kaplan–Meier and Cox regression analyses to evaluate factors associated with overall survival (OS). Results Between July 2012 and June 2017, 341 patients with suspected BL presented to the BL Project. One hundred eighty patients with a pathology‐based diagnosis were included in this study. The median age was seven years (interquartile range, 5–9), 74% lived ≥100 km from the Uganda Cancer Institute, 61% had late‐stage disease, 84% had ECOG performance status < 3, 63% reported B‐symptoms, and 22% showed neurologic symptoms. Fewer than 10% abandoned therapy. The four‐year OS rate was 44% (95% CI, 36%–53%). In a multivariate model, ECOG status was significantly associated with mortality. Conclusion The BL Project reduced effects of lacking supportive care and oncology resources, and allowed patients from Uganda to receive curative intent therapy with minimal loss to follow‐up. Nonetheless, OS remains unacceptably low. Improved therapeutic approaches to endemic BL are urgently needed in Africa.

Background Perceptions of high cost and resource intensity remain political barriers to the prioritization of childhood cancer treatment programs in many low‐ and middle‐income countries (LMICs). Little knowledge exists of the actual cost and cost‐effectiveness of such programs. To improve outcomes for children with Burkitt lymphoma (BL), the most common childhood cancer in Africa, the Uganda Cancer Institute implemented a comprehensive BL treatment program in 2012. We undertook an economic evaluation of the program to ascertain the cost‐effectiveness of BL therapy in a specific LIC setting. Methods We compared the treatment of BL to usual care in a cohort of 122 patients treated between 2012 and 2014. Costs included variable, fixed, and family costs. Our primary measure of effectiveness was overall survival (OS). Patient outcomes were determined through prospective capture and retrospective chart abstraction. The cost per disability‐adjusted life‐year (DALY) averted was calculated using the World Health Organization’s Choosing Interventions That Are Cost‐Effective (WHO‐CHOICE) methodology. Results The 2‐year OS with treatment was 55% (95% CI, 45% to 64%). The cost per DALY averted in the treatment group was US$97 (Int$301). Cumulative estimate of national DALYs averted through treatment was 8607 years, and the total national annual cost of treatment was US$834,879 (Int$2,590,845). The cost of BL treatment fell well within WHO‐CHOICE cost‐effectiveness thresholds. The ratio of cost per DALY averted to per capita gross domestic product was 0.14, reflecting a very cost‐effective intervention. Conclusion This study demonstrates that treating BL with locally tailored protocols is very cost‐effective by international standards. Studies of this kind will furnish crucial evidence to help policymakers prioritize the allocation of LMIC health system resources among noncommunicable diseases, including childhood cancer.