Patterns of Distribution of Childhood Cancer in Africa

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1 Journal of Tropical Pediatrics, 2015, 61, doi: /tropej/fmv005 Advance Access Publication Date: 26 February 2015 Original paper Patterns of Distribution of Childhood Cancer in Africa by D. Cristina Stefan 1,2 1 Department of Paediatrics and Child Health, Tygerberg Hospital and Stellenbosch University, Tygerberg, Cape Town, South Africa 2 South African Medical Research Council (SAMRC), Cape Town, South Africa Correspondence: D. Cristina Stefan, South African Medical Council, Parrow, Cape Town 7550, South Africa. Tel: þ <cristina.stefan@mrc.ac.za>. SUMMARY Background: Very little is known about the regional variation in the incidence of childhood malignancies in Africa. The aim of the study was to perform a comprehensive analysis of the distribution of childhood cancer in Sub-Saharan Africa and compare the results to the Globocan estimations. Methods: A letter of invitation to participate was sent to all centers in Africa registered with the International Agency for Research on Cancer and to all African centers registered with AORTIC and SIOP Africa, requesting similar information as in CanReg 4. Childhood cancers were defined as those occurring below the age of 15 years. The data requested was from 2000 to The malignancies were classified and coded according to the International Classification of Childhood Cancer, 2004 system. Data obtained were analyzed using EpiInfo and Statistica 10 software. Information regarding the estimation of the numbers and incidence of the top 5 childhood cancers in specific countries was obtained from Globocan Web site. Results: There were 21 centers included in the study from 18 Sub-Saharan African countries. The data analyzed differed from center to center and included cases from 1985 to The proportion of childhood cancer out of all cancers ranged between 1.4% in Ghana to 10.0% in Rwanda. In Southern Africa, was the most common malignancy in children in Mozambique (15.8% of all cases) and the second most common in Zambia (15.6%) and in Malawi (12.4%). In Eastern Africa, Uganda recorded as the most common tumor in children (22.0%), while two Kenyan centers reported mainly Burkitt lymphoma (25.1 and 37.1%, respectively). In Central Africa, Congo classified retinoblastoma as the most common childhood cancer with an incidence of 20.1%. In Western Africa, Non-Hodgkin lymphoma was the most common in Ghana (53.6%), in Ivory Coast (73.6%) and in Mali (32.7%). Nephroblastoma remains the most common solid tumor in Africa exceeding 10% of total pediatric cancers in many countries (Rwanda 21.3%, Senegal 22%, Ivory Coast 14.5%, Mali 17.6%, Congo 15.5%, etc). Conclusion: Unlike developed countries, lymphomas, nephroblastoma, and retinoblastoma were the most common pediatric tumors in Africa. Globocan estimations despite bringing significant contribution to the registration map cannot replace the data from local hospital and population- registries. All efforts should be directed in developing functional and reliable childhood cancer registries across the African continent. VC The Author [2015]. Published by Oxford University Press. All rights reserved. For Permissions, please journals.permissions@oup.com 165

2 166 Patterns of Distribution of Childhood Cancer in Africa KEYWORDS: distribution, cancer, childhood, developing countries, Africa. INTRODUCTION Very little is known about the regional variation in the incidence of various childhood malignancies in Africa. Most studies published are addressing one disease only, or report findings from a restricted geographical area. There are no known dedicated childhood cancer registers in Africa with the exception of the one kept by the South African Children s Cancer Study Group, presently at Tygerberg Hospital, Faculty of Health Sciences, University of Stellenbosch, South Africa. However, many centers enter children in the same cancer register with adults. Most of African cancer registers are not population but hospital registers, on records of admitted patients. There are also a few registers on the pathology findings on the biopsy or operative specimens [1]. The total population coverage is approximately 18 million with data until 2007 representing less than 0.18% of the African population which is estimated at a little more than 1 billion inhabitants [2] Children represent 41% of the total people living in Africa; in some countries they even constitute more than half of the population. Assuming a rate of childhood malignancies of 88 per million (Globocan 2012), the estimated annual number of new childhood cancer cases/year in Africa would be around A recent publication by Magrath showed that the proportion of childhood cancer of 4.8% of all malignancies is higher in Africa than in developed countries and reflects the higher proportion of children relative to the general population [3]. The true incidence of childhood cancer in Africa remains difficult to determine. Any estimation of the burden of disease has to rely on data provided by the sparse existing registries. The most detailed and comprehensive attempt at such estimation was done by the Globocan team at The International Agency for Research in Cancer, in However, the Globocan statistics for Africa are mostly on extrapolation of older data from registries covering just limited regions within the countries studied; these data were often adjusted using figures from neighboring countries. For countries where no data were available, the figures reported in Globocan are simply those of the adjacent countries. Notwithstanding the value of the Globocan estimates of the cancer incidence, prevalence and mortality, they leave room for updates and corrections This study collates figures from a number of cancer registries in Sub-Saharan Africa and attempts to provide an alternative estimation of childhood cancers on reporting the data from the local units. The study also provides a comparison between the estimates given by Globocan and the reported data sent by the African participants. Methods Study population This study included all children with cancer aged less than 15 years, entered in various local-, regional- or national- registries from 18 Sub-Saharan African countries (Table 1). A letter of invitation to participate was sent to all cancer registries in Africa on the International Agency for Research on Cancer (IARC) membership list and to all African registries centers registered with African Organization for Research and Training in Cancer (AORTIC) and International Society for Pediatric Oncology (SIOP) Africa. The letter requested the same information as in CanReg 4: date of birth, date of diagnosis, age, gender, diagnosis, ethnic group, address and information about the tumor [topography, morphology, stage, International Classification of Diseases (ICD) codes and follow up (if completed); Fig. 1 (Canreg form)]. The time interval studied was from 2000 to However, many centers sent additional information which was then analyzed and included in the study (from 1985 to 2012). All malignant and all intracranial and intraspinal tumors were included. The malignancies were classified and coded according to the International Classification of Childhood Cancer, 2004 system. The analysis of the data was done by using CanReg4 (when available) and statistical packages such as Statistica10. Some centers sent already analyzed reports. Statistical analysis The statistical significance of findings was tested by using Statistica 10 software. Maps reflecting the

3 Patterns of Distribution of Childhood Cancer in Africa 167 Table 1. List of the units from Eastern Africa Country Type of Time period Number of cases Most frequent cases Globocan estimations 2012 Kenya Kenya Eldoret (region Kijabe (regional Non-Hodgkin 22.63% Leukemia 15.82% Burkitt lymphoma14.64% Nephroblastoma 8.3% Soft tissue tumors 70% Burkitt lymphoma 16.6% NHL 8.5% Hodgkin lymphoma 7.6% 3.5% Nephroblastoma 3.4% Rwanda Lymphomas 27% Nephroblastoma 21.3% Leukemia 10.8% Osteosarcoma 8.2% Brain tumors 6 % Sudan Sudan Tanzania Uganda Central Sudan (regional Sudan (hospital series) Bugando Medical Centre National cancer Registry (population Lymphomas 42.8% Leukemia 19.8% Nephroblastoma 12.8% Soft Tissue tumors 7% Bone tumor 5.9% Lymphomas 35% Leukemia 26% Nephroblastoma 13% Soft tissue tumors Naso pharyngeal carcinomas 3.8% Lymphoma BL 41% Retinoblastoma 18% Wilms 14% Leukemia 8% Neuroblastoma 6% % Burkitt lymphoma 20.52% Non-Hodgkin 12.81% Leukemia 6.87% Nephroblastoma 6.78% NHL 17.7% Leukemia 14.6% KS 11.2% Nephroblastoma 6.3% Brain tumors 6.3% NHL 15.9% Leukemia 9.9% 6.4% Kidney 5% HL 4.1% Nephroblastoma 19.7% NHL 13.7% Leukemia 12.7% Brain 6.6% Nasopharinx 2.3% 19.7% Leukemia 7.1% NHL 6.7% Kidney 3.8% HL 3% NHL 26.5% 13.5% Leukemia 9.8% Kidney 7% HL 4.3% NHL: Non Hodgkin Lymphoma; HL: Hodgkin Lymphoma; KS: ; BL: Burkitt Lymphoma.

4 168 Patterns of Distribution of Childhood Cancer in Africa FIG. 1.Map of Africa with the most common childhood cancer per country analyzed. distribution of most frequent cancers across the continent, as well as correlation with the population (for national registries) in various geographical regions, were constructed (map with the most common cancer per country). Ethical consideration Ethical approval and consent to participate were obtained locally by each center and also were granted by the Health Research Ethics Committee, University of Stellenbosch. Patients were anonymous, as the data were sent and recorded without any private details. The principal investigator was granted an International Cancer Technology Transfer Fellowships (ICRETT) fellowship from the International Union for Cancer Control (UICC) in 2011 in order to conduct the study. RESULTS In the study, there were 21 centers included from 18 countries in Sub-Saharan Africa. The data analyzed differed from center to center and included cases from 1985 to There were no dedicated childhood cancer registries and no reporting center had as chair a pediatric oncologist. The study did not asses the data from Groupe Franco Africain d oncologie Pediatrique (GFAOP). The percentage of childhood cancer ranged between 1.4% in Ghana to 9.4% in Rwanda.

5 Patterns of Distribution of Childhood Cancer in Africa 169 Table 2. List of the units from Southern Africa Country Type of Time period Number of cases Most frequent cases Globocan estimations 2012 Lesotho 1 unit Brain tumors 18.8% Leukemia 18.3% Nephro 16.3% Lymphomas 10.1% Retinoblastoma 9.6% Malawi Mozambique Namibia National cancer Population Maputo (population 1 Unit Population Burkitt lymphoma 45.75% 12.35% Retinoblastoma 7.48% Non-Hodgkin 6.77% Nephroblastoma 5.52% % Non-Hodgkin 14.95% Burkitt lymphoma 14.23% Nephroblastoma 9.12% Soft tissue tumors 58.26% Leukemia 22.75% Retinoblastoma 16.40% Nephroblastoma 12.70% Neuroblastoma 6.35% Burkitt lymphoma 5.82% South Africa Population Leukemia 27.45% Lymphoma 12.92% Nephroblastoma 12.89% CNS tumors 10.56% Sarcomas 8.68% Zambia National cancer Non-Hodgkin 22.7% 15.6% (population Burkitt lymphoma 9.0% Nephroblastoma 7.5% Retinoblastoma 6.5% Zimbabwe NCR Soft tissue sarcomas (20.9%) (KS 12.2% of all) Leukemia 16.9% Lymphoma 14.5% Nephroblastoma 12.8% CNS tumors 11.0% No data available NHL 44.2% 15.1% Nephroblastoma 6.8% Liver 2.7% HL 2.4% NHL 31.5% 22.1% Leukemia 12.9% Brain 2.7% Nephroblastoma 2.7% 27.2% Nephroblastoma 9% Hepatic tumors 9% NHL 9% Leukemia 20.9% Brain18% Kidney 11.1% NHL 8.4% Kaposi 5% NHL 22.6% 21% Leukemia 7.8% Kidney 7% Brain 4.6% 39.6% Kidney 13.7% Leukemia 9.8% Brain 8% NHL 4% CNS: Central Nervous System; NCR: National Cancer Registry.

6 170 Patterns of Distribution of Childhood Cancer in Africa Table 3. List of the units from Western Africa Country Type of Time period Number of cases Most frequent cases Globocan estimations 2012 Ivory Coast Ghana (Accra) Mali (Bamako) Nigeria 1 center Treichville (population Accra 1 unit (hospital series) 1 unit (population Jos (Central Nigeriaregional The Globocan reported the lowest percentage in Namibia (0.8%) and the highest in Mali (12.3%). In Southern Africa, was the most common malignancy in children in Mozambique (15.8% of all cases) and the second most common in Zambia (15.6%) and in Malawi (12.3%) (Table 2) Burkitt lymphoma 73.6% Nephroblastoma 14.5% Leukemia 4.5% Hodgkin lymphoma 3.9% Retinoblastoma 1.8% Lymphomas 53.6% CNS tumors 12.7% Nephroblastoma 10.6% Leukemia 6.7% Hepatic tumors 4% NHL 32.7% Nephroblastoma 17.6% Hodgkin lymphoma 8.4% Retinoblastoma 5.8% Rabdomyosarcoma 3.3% Rhabdomyosarcoma 31% NHL 19.5% Retinoblastoma 8% Nephroblastoma 5% Hodgkin lymphoma 3.5% Nigeria Zaria Burkitt Lymphoma % (Northern Retinoblastoma 14.2% Nigeria Rhabdomyosarcoma % regional NHL 9.5% Nephroblastoma 9.5% Senegal Dakar Nephroblastoma 22% Retinoblastoma 19% Leukemia 13% Lymphoma 12% Hodgkin lymphoma 9% NHL 16.3% Nephroblastoma 15.2% Hodgkin lymphoma 4.9% Leukemia 2.46% Oral cavity 1.79% Nephroblastoma 20.9% NHL 17% Hepatic tumors 15% Hodgkin lymphoma 5.6% Brain tumors4.8% NHL 19.7% Nephroblastoma 18.4% Leukemia 4.6% HL 4.2% Bladder 4.1% NHL 27.5% Nephroblastoma 10.4% HL 4.6% Leukemia 4.2% Liver 4.1% Nephroblastoma 17% NHL 15% Leukemia 5.8% HL 4.3% Bladder tumors 3.9% Non-Hodgkin lymphoma (predominantly Burkitt lymphoma) ranged first in Zambia (31.7%) and in Malawi (45.7%). In Eastern Africa, Uganda recorded as the most common tumor in children (22.03%), while two Kenyan centers reported mainly Burkitt lumphoma (25.1% and 37.1%, respectively).

7 Patterns of Distribution of Childhood Cancer in Africa 171 Table 4. List of the units from Central Africa Country Type of Time period Number of cases Most frequent cases Globocan estimations 2012 Congo (Brazzaville) 1 unit (population In Western Africa, Non-Hodgkin lymphomas (including Burkitt; 53.6%) remain the most common in Ghana, in Ivory Coast (73.6%) and in Mali (32.7%) (Table 3). Nephroblastoma is one of the most common solid tumors in Africa with an incidence exceeding 10% in many countries (Ivory Coast 14.5%, Mali 17.6%, Congo 15.5%, Sudan 13%, etc). In Rwanda, nephroblastoma was the most common childhood cancer in girls with an unexpected incidence of 26%. It was also reported on top of list in Senegal with a 22% incidence. The histopathology confirmation ranged between 49% in Nigeria to above 80% in Namibia, Mali, Lesotho and South Africa. Most patients were reported by South Africa with (over 20 years) and 119 in Mali (over 4 years). No selection criteria for centers were applied in the survey. Table 1 contains the list of the countries of residence of the respondents. No reports were received regarding the follow-up or the date of last contact. In none of the centers was the chairperson of the a pediatric oncologist (except in South Africa). The top 5 most common childhood cancers in 18 units studied are presented in table with a comparison of their corresponding Globocan estimations. For practical reasons, Burkitt lymphoma was reported separately (when data available) from the rest of Non-Hodgkin Lymphoma. DISCUSSION There is no attempt yet, as far as could be determined, to characterize the global and regional distribution of incidence of major childhood cancers in Africa Retinoblastoma 20.1% Leukemia 19.4% Nephroblastoma 15.6% Lymphoma 14.1% Hepatoblastoma 5.9% Nephroblastoma 19% Leukemia 12% Hepatoblastoma 7.5% NHL 7.5% Brain tumors 4.5% Data collected and analyzed identified typical patterns of cancers in Sub-Saharan African children. The incidence of childhood cancer in Africa is higher than previously described in the literature and needs further research. Most of the childhood cancers suspected and diagnosed were referred and treated in specialized units. The centers which contributed to the data were all referring centers for the treatment of childhood cancer in their countries. The overall incidence of childhood cancer increased by 1% per year over the past 3 decades of the 20th century in Europe, North America, Australia although the rate of increase seems to have leveled off over the past decade [4, 5]. Population- cancer registries around the world report incidences between 50 and 200 per million children per year. The childhood cancer incidence in Africa varied between 120 per million in Zimbabwe [6] to 448 per million in South Africa [7] and 55 per million in Congo [8]. The distribution of childhood cancer in Africa has changed in the past decade due to the human immunodeficiency virus (HIV) epidemic and the appearance of. Southern Africa remains the region mostly affected by this HIVrelated malignancy. The spectrum of malignancies in Africa is also different than those reported in the developed countries. Acute lymphoblastic leukemia is the most common childhood cancer diagnosed worldwide except for the African continent. It remains on the top of the list for two of the centers analyzed: Namibia (incidence 22.7%) and South Africa (27.4%).

8 172 Patterns of Distribution of Childhood Cancer in Africa Improved diagnostics and suspicion of all on the clinical examination and correlated with specific blood results might result in increasing number of patients diagnosed with leukemia. Brain tumors are the second most malignancy reported in children worldwide. In Africa brain tumors are difficult to be diagnosed due to the lack of necessary equipment, financial implications and in most cases due to wrong assumption of differential diagnoses such as cerebral malaria, tuberculous meningitis, bacterial meningitis, etc. Lesotho, a small country surrounded by South Africa, with a population of just above 2 million and children who represent a third of the total population reported brain tumors as the most common (18.8%) followed by leukemia (18.3%). South Africa, the neighboring country reported only 10.8% brain tumors (previous incidence calculated of 3.05 per million being one of the lowest of the [7]. All children from Lesotho are diagnosed and treated in Bloemfontein (South Africa) and all their cases were pathologically confirmed. Nephroblastoma remains one of the most curable cancers in children, especially if diagnosed early. The incidence of nephroblastoma in developed countries does not exceed 6 7% [9], while in Africa is reported as the most common cancer in children in Rwanda (in girls) and in Senegal with incidence above 20%. It is also noted as in the first three most common cancers with incidence above 15% in other units (Cote d Ivoire, South Africa, Sudan, Ghana, Congo, Lesotho, Zimbabwe and Tanzania). The other childhood cancer which is easy to diagnose and is highly curable if detected early is retinoblastoma. Incidences reported by first world countries range between 2 and 4 per million while in Africa is the most common cancer reported in Congo (one in four children: 24.7% of all pediatric cancers) [8] and with a high percentage in Tanzania (18%) (Table 4), Namibia (16.4%) and Malawi (7.8%). The epidemiology of childhood cancer in Africa differs significantly to the epidemiology of malignancies described in developed countries as well as their way of distribution. Childhood cancer is a relatively rare disease but highly curable and cost-effective. The incidence of childhood cancer is not expected to increase in Africa but an increased number of reported cases might occur with the improving of the quality of registries and the increase in awareness, knowledge, diagnostic tools and affordability. Trend changes expected to occur in Africa are related to a decrease in the number of children with with the major reduction of newly infected HIV patients, reduced perinatal transmission and vast access to antiretroviral therapy. In the same context of improving socioeconomic conditions, it is expected to report a higher number of case of leukemia, a cancer correlated with higher level of development, such as delayed exposure to common infections, population mixing and reproductive behavior. Access to more sophisticated radiological equipment will improve the diagnosis of brain tumor for which radiotherapy plays an essential role. Globocan is a useful tool to provide estimates of the incidence of mortality and prevalence from major type of cancers, for 184 countries in the world [10]. However, when comparing data from local registries to Globocan, major differences were recorded in a number of countries. Congo, Ghana, Namibia, South Africa, Sudan. Other smaller countries had no information available (Lesotho). It is essential to invest in hospitaland population- registries. In each African country, registries are required to include complete information regarding cancers in children below the age of 15 years in order to be able to describe correctly the epidemiology and the incidence of childhood cancers in Africa. The cost of a national dedicated pediatric in Africa was calculated at R /month (90 Euro) for the South African tumor, cost which is supported by the parent organization group Childhood Cancer Foundation South Africa (CHOC). Similar initiatives could follow in different other centers. Limitations of the study In this survey, no selection criteria for centers were applied. The questionnaire and the invitation to participate were sent to all units available from the directory of IARC and AORTIC.

9 Patterns of Distribution of Childhood Cancer in Africa 173 The registries which reported the data were part of the population- registries or belonged to the referral centers where the patients were treated. The data collected were, retrospectively, not always complete and not all cases were histologically confirmed. The study despite bringing a significant contribution to the distribution of Sub-Saharan African childhood cancer cannot assume that all cancers were reported or included in the analysis. No reports were received regarding the follow-up or the date of last contact. In none of the centers was the chairperson of the a pediatric oncologist (except in South Africa). Conclusions Understanding the incidence distribution of pediatric cancers and its changes over time is a fundamental prerequisite for the design of sound clinical and public health programs, as well as research programs, to support the health-care effort required in order to cure these afflictions. These findings are useful to advocate for services and training. New prospective studies are needed. This information could open new doors for research in cancer epidemiology. FUNDING The author received an ICRETT fellowship from UICC to train in cancer registration at IARC in ACKNOWLEDGEMENTS The author thanks all collaborators and tumor registries from the centers which contributed with data. REFERENCES 1. (11 March 2014, date last accessed). 2. Forman D, Bray F, Brewster DH, et al. (eds). Cancer Incidence in Five Continents. Vol X (electronic version). Lyon, IARC, (10 January 2014, date last accessed). 3. Magrath I, Eppelman S. Cancer in adolescents and young adults in countries with limited resources. Curr Oncol Rep 2013;15: doi: /s Baade PD, Youlden DR, Valeery PC, et al. Population survival estimates for childhood cancer in Australia during the period Br J Cancer 2010;103: doi: /sj. Bjc Baba S, Ioka A, Tsukuma H, et al. Incidence and survival trends for childhood cancer in Osaka, Japan, Cancer Sci 2010;101: doi: /j Chokunonga E, Borok MZ, Chirenje ZM, et al. Cancer incidence in Harare Triennal report African Cancer Registry Network. 7. Stefan DC, Stones DK. The South African Paediatric Tumour Registry 25 years of activity. SAMJ 2012;102: Nsonde Malanda J, Nkoua Mbon JB, Bambara AT, et al. Douze annee de fonctionnement du register des cancers de Brazaville. Buletin du Cancer 2013;100:fevr Peter K. Epidemiology of childhood cancer. Cancer Treatment Rev 2010;36: /j.ctrv Globocan. globocan.iarc.fr (11 March 2014, date last accessed).