Presentation and Outcomes of Childhood Cancer Patients at Uganda Cancer Institute.

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.

Esophageal cancer male to female incidence ratios in Africa: A systematic review and meta-analysis of geographic, time and age trends.

Esophageal squamous cell carcinoma (ESCC) remains the predominant histological subtype of esophageal cancer (EC) in many transitioning countries, with an enigmatic and geographically distinct etiology, and consistently elevated incidence rates in many Eastern and Southern African countries. To gain epidemiological insights into ESCC patterns across the continent, we conducted a systematic review and meta-analysis of male-to-female (M:F) sex ratios of EC age-standardised (world) incidence rates in Africa according to geography, time and age at diagnosis. Data from 197 populations in 36 countries were included in the analysis, based on data from cancer registries included in IARC's Cancer Incidence in Five Continents, Cancer in Africa and Cancer in Sub-Saharan Africa reports, alongside a systematic search of peer-reviewed literature. A consistent male excess in incidence rates overall (1.7; 95% CI: 1.4, 2.0), and in the high-risk Eastern (1.6; 95% CI: 1.4, 1.8) and Southern (1.8; 95% CI: 1.5, 2.0) African regions was observed. Within the latter two regions, there was a male excess evident in 30-39 year olds that was not observed in low-risk regions. Despite possible referral biases affecting the interpretability of the M:F ratios in place and time, the high degree of heterogeneity in ESCC incidence implies a large fraction of the disease is preventable, and directs research enquiries to elucidate early-age exposures among young men in Africa.

A Population-Level Evaluation of the Effect of Antiretroviral Therapy on Cancer Incidence in Kyadondo County, Uganda, 1999-2008.

BACKGROUND: The introduction of antiretroviral therapy (ART) in the United States and Europe has led to changes in the incidence of cancers among HIV-infected persons, including dramatic decreases in Kaposi sarcoma and non-Hodgkin lymphoma, and increases in Hodgkin lymphoma, 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 the Joint United Nations Program on HIV/AIDS 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% confidence interval: 0.91 to 0.99, P = 0.02] and stomach cancer decreased by 13% [IRR = 0.87 (95% CI: 0.80 to 0.95), P = 0.002]. Conversely, incidence of non-Hodgkin lymphoma increased by 6% [IRR = 1.06 (95% CI: 1 to 1.12), P = 0.05], liver cancer by 12% [IRR = 1.12 (95% CI: 1.04 to 1.21), P = 0.002], prostate cancer by 5% [IRR = 1.05 (95% CI: 1 to 1.10), P = 0.05], and breast cancer by 5% [IRR = 1.05 (95% CI: 1 to 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. CONCLUSIONS: 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.

The incidence of oesophageal cancer in Eastern Africa: identification of a new geographic hot spot?

The incidence of oesophageal cancer (OC) varies geographically, with more than 80% of cases and deaths worldwide occurring in developing countries. The aim of this study is to characterize the disease burden of OC in four urban populations in Eastern Africa, which may represent a previously undescribed high-incidence area. Data on all cases of OC diagnosed between 2004 and 2008 were obtained from four population-based cancer registries in: Blantyre, Malawi; Harare, Zimbabwe; Kampala, Uganda; and Nairobi, Kenya. Age-standardized incidence rates (ASRs) were calculated for each population, and descriptive statistics for incident cases were determined. In Blantyre, 351 male (59%) and 239 (41%) female cases were reported, with ASRs of 47.2 and 30.3. In Harare, 213 male (61%) and 134 (39%) female cases were reported, with ASRs of 33.4 and 25.3, respectively. In Kampala, 196 male (59%) and 137 female (41%) cases were reported, with ASRs of 36.7 and 24.8. In Nairobi, 323 male (57%) and 239 female (43%) cases were reported, with ASRs of 22.6 and 21.6. Median age at diagnosis was significantly different among the four populations, ranging from 50 years in Blantyre to 65 years in Harare (p<0.0001). Except in Nairobi, incidence among males was significantly higher than among females (p<0.01). Squamous cell OC was the predominant histologic subtype at all sites. ASRs at all four sites were remarkably higher than the mean worldwide ASR. Investigation to evaluate potential etiologic effects of dietary, lifestyle, environmental, and other factors impacting the incidence in this region is needed.

Trends in the incidence of cancer in Kampala, Uganda 1991-2010.

The Kampala cancer registry is the longest established in Africa. Trends in incidence rates for a 20-year period (1991-2010) for Kyadondo County (Kampala city and a rural hinterland) illustrate the effects of changing lifestyles in urban Africa, and the effects of the epidemic of HIV-AIDS. There has been an overall increase in the risk of cancer during the period in both sexes, with incidence rates of major cancers such as breast and prostate showing particularly marked increases (3.7% and 5.2% annually, respectively). In the 1960s cancer of the oesophagus was the most common cancer of men (and second in women), and incidence in the last 20 years has not declined. Cancer of the cervix, always the most frequent cancer of women, has shown an increase over the period (1.8% per year), although the rates appear to have declined in the last 4 years. HIV prevalence in adults in Uganda fell from a maximum in 1992 to a minimum (about 6%) in 2004, and has risen a little subsequently, while availability of antiretroviral drugs has risen sharply in recent years. Incidence of Kaposi sarcoma in men fell until about 2002, and has been relatively constant since then, while in women there has been a continuing decline since 2000. Other HIV related cancers-non-Hodgkin lymphoma of younger adults, and squamous cell carcinoma of conjunctiva-have shown major increases in incidence, although the former (NHL) has shown a small decline in incidence in the most recent 2 years.

Mind the gaps: a qualitative study of perceptions of healthcare professionals on challenges and proposed remedies for cervical cancer help-seeking in post conflict northern Uganda.

BACKGROUND: There are limited data on perceptions of health professionals on challenges faced by cervical cancer patients seeking healthcare in the developing countries. We explored the views of operational level health professionals on perceived barriers to cervical screening and early help-seeking for symptomatic cervical cancer and the proposed remedies to the challenges. METHODS: Fifteen key informant interviews were held with health professionals including medical directors, gynecologists, medical officers, nurses and midwives in the gynecology and obstetrics departments of two hospitals in northern Uganda during August 2012 to April 2013. We used content analysis techniques to analyze the data. RESULTS: Health professionals' perceived barriers to cervical cancer care included: (i) patients and community related barriers e.g. lack of awareness on cervical cancer and available services, discomfort with exposure of women's genitals and perceived pain during pelvic examinations, and men's lack of emotional support to women (ii) individual healthcare professional's challenges e.g. inadequate knowledge and skills about cervical cancer management; (iii) health facility related barriers e.g. long distances and lack of transport to cervical cancer screening and care centers, few gynecologists and lack of pathologists, delayed histology results, lack of established palliative care services and inadequate pain control; and (iv) health policy challenges e.g. lack of specialized cancer treatment services, and lack of vaccination for human papilloma virus. Other challenges included increased number of cervical cancer patients and late stage of cervical cancer at presentations. CONCLUSIONS: Operational level healthcare professionals in northern Uganda reported several practical challenges facing cervical cancer care that influence their decisions, management goals and practices. The challenges and proposed remedies can inform targeted interventions for early detection, management, and control of cervical cancer in Uganda.

Clinical oncology in resource-limited settings.

Infectious Agents and Cancer is introducing a new section of Clinical Oncology with the main objective of stimulating debate through articles published in the section. Infectious diseases have been the major causes of morbidity and mortality in human populations, and have dominated the medical approach to clinical and public health. Successful efforts to control mortality from acute infections have paved the way for chronic, mostly indolent, infections to become major causes of morbidity. Cancer, hitherto thought to be rare in resource-limited settings, is becoming a major contributor. The changes in mortality patterns are due, in part, to diseases linked to rapid changes in lifestyle, urbanization, and pollution. These diseases include many of the non-infection associated cancers. However, there is a dearth of information about the burden, pathogenesis, and therapeutic approaches about cancer in resource-limited countries. There are also substantial other challenges, including economic, infrastructure, technology, and personnel. The Journal advocates for interactive local-global (lo-bal) efforts to generate relevant knowledge about cancer burden, pathogenesis, and therapeutic approaches using a bottom-up approach to sharpen the focus on local and global relevance of research and clinical and public practice, particularly in resource-limited countries. The section on Clinical Oncology in Infectious Agents and Cancer will harness these "lo-bal" strategies to reduce substantially the time from concept, discovery, and development and implementation of locally and globally applicable diagnostic and therapeutic technologies.

Kaposi sarcoma trends in Uganda and Zimbabwe: a sustained decline in incidence?

Trends in Kaposi sarcoma (KS) incidence over four decades were described for Zimbabwe and Uganda. KS data were retrieved from the population-based cancer registries of Bulawayo (1963-1971) and Harare (1990-2005), Zimbabwe and Kyadondo, Uganda (1960-1971 and 1991-2007). Joinpoint regression models were used to analyze time trends of KS incidence. Trends were compared to HIV/AIDS trends and were also described as rates versus birth cohort by age. In both countries, an increased incidence of KS accompanied the emergence of the HIV/AIDS epidemic (p-value < 0.0001). In Zimbabwe, KS incidence (both sexes, all ages) changed in parallel to that of HIV/AIDS prevalence, whereas in Uganda, despite an observed decrease in HIV/AIDS prevalence since 1992, we observed a decrease in KS incidence in men younger than 50 years (Annual Percent Change, APC after 1991 = -4.5 [-5.6; -3.4], p-value < 0.05) but not in men aged >50 years (APC after 1991 = 1.0 [-2.8; 5.0]) nor in women (APC = 1.0 [-0.6; 2.6]). In both populations, a period effect at older ages was observed, with initial increases in incidence in men followed subsequently by a downturn in rates of the same magnitude. The uniformly declining rates in younger men (aged less than 30 years) suggested that a recent cohort effect was also in operation with a reduced risk in generations born after the mid-1950s in Uganda and in the mid-1960s in Zimbabwe. The combined introduction of antiretroviral therapy and effective prevention programmes against HIV/AIDS appeared to be the key contributors to the KS decline observed in both Uganda and Zimbabwe.

Changing cancer incidence in Kampala, Uganda, 1991-2006.

Incidence rates of different cancers have been calculated for the population of Kyadondo County (Kampala, Uganda) for a 16-year period (1991-2006). This period coincides with continuing social and lifestyle changes and the peak and subsequent wane of the epidemic of HIV-AIDS. There has been an overall increase in the risk of cancer during the period in both sexes, with the incidence rates of cancers of the breast and prostate showing particularly marked increases (4.5% annually). Prostate cancer is now the most common cancer in men. The incidence of cancer of the esophagus, formerly the most common cancer in men and second in frequency in women, has remained relatively constant, whereas the incidence of cancer of the cervix, the most common malignancy in women, continues to increase. Since the early 1990s the incidence of Kaposi sarcoma (KS) in men has declined, and while remaining relatively constant in women, it has been diagnosed at progressively later ages. The rates of pediatric KS have declined by about 1/3rd. The incidence of squamous cell cancers of the conjunctiva has also declined since the mid 1990s. Cancer control in Uganda, as elsewhere in sub-Saharan Africa, involves meeting the challenge of emerging cancers associated with westernization of lifestyles (large bowel, breast and prostate); although the incidence of cancers associated with poverty and infection (liver, cervix, esophagus) shows little decline, the residual burden of the AIDS-associated cancers remains a major burden.

Association between invasive cancer of the cervix and HIV-1 infection in Tanzania: the need for dual screening.

BACKGROUND: Cancer of the cervix is the second commonest malignancy in females worldwide and is the leading malignancy among women in Tanzania. Cancer of the cervix has been strongly associated with Human Papilloma Virus (HPV) which is a sexually transmitted disease. However, the role of HIV-1 in the aetiology of cancer of the cervix is less clear. Studies suggest that HPV and HIV-1 infection are synergistic and therefore their dual occurrence may fuel increased incidence of cancer of the cervix and AIDS. We therefore conducted a study to determine the association between cancer of the cervix and HIV-1. METHODS: The study was carried out in Ocean Road Cancer Institute, Dar-es-salaam, Tanzania between January and March 2007. A hospital-based case control design was used to study 138 cases and 138 controls. The cases were consenting women 18 years and above with histologically confirmed squamous cell carcinoma of the cervix, while the controls were consenting non-cancer adult women attendants or visitors. The participants were counselled and tested for HIV-1 and interviewed to assess risk factors for cancer of the cervix and HIV-1. Estimation of risk was done by computing odds ratios and confidence intervals. Confounding and interaction between the factors were assessed using logistic regression. RESULTS: HIV-1 prevalence was much higher among the cases (21.0%) than among the controls (11.6%). In logistic regression, HIV-1 was associated with cancer of the cervix (OR = 2.9, 95% CI = 1.4-5.9). Among the cases the mean age was lower for HIV-1 infected (44.3 years) than HIV-1 uninfected women (54 years, p = 0.0001). CONCLUSION: HIV-1 infection is associated with invasive cancer of the cervix. Resource-constrained countries with a high burden of HIV-1 and cervical cancer should adopt a high-risk approach that targets HIV-1 positive women for screening of cervical cancer initially by utilizing HIV/AIDS resources.