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Table 2 Characteristics of included studies

From: Mapping evidence on the risk factors associated with pediatric cancers in sub-Saharan Africa: a scoping review

Author and date

Country and Period

Study aim

Study design

Study population characteristics

Outcome

Risk factor

Population and age group

F%

M%

Moore et al. 2008 [27]

South Africa (1988-2006).

To assess recent changes in the prevalence and surgical management of liver tumours in South African children.

Retrospective chart review.

274 Children with liver tumours (0-14 years) from South African Children’s Cancer Study Group (SACCSG) Tumour Registry and as well as the individual POUs)

45.9

54.1

• Hepatoblastoma presented at a mean age of 2.16 years and was not identified in children over 4 years.

• HCC was predominant in older patients (mean age: 10.48 years) but 6% was presented in children younger 8 years of age.

• There was an increase in the incidence of vascular tumours, probably due to an increase in Kaposi-like sarcoma in retrovirus -positive patients.

Age

Gender

Ethnicity

• 94 % of the children with HCC were black.

• In 69% of HCC patients elevated Hepatitis B titres were identified.

• Hepatitis B vaccination led to an observed decrease in the incidence of HCC.

• There was a higher percentage of males indicating HBsAg predominance in males.

Infections (Hepatitis B)

Mulama et al. 2014 [28]

Kenya

To examine whether sickle cell trait, which is associated with protection from severe malaria and hyper-parasitaemia, decreases endemic BL risk. Secondary aim was to measure peripheral EBV load as an indicator of viral control and associate levels with HbAA/AS genotype

Case control study

306 children with a confirmed diagnosis of eBL and 537 geographically defined and ethnically matched controls.

40

60

• Sickle cell trait does not protect against eBL for children residing in malaria holoendemic areas after controlling for ethnicity.

• Although not in line with the aim this study indirectly suggests that Epstein Barr Virus and Plasmodium falciparum coinfections are contributing risk factors to endemic Burkitt lymphoma (BL).

Infection (EBV and malaria)

Rainey et al. 2007 [36]

Kenya (1988-1997)

To determine if strong associations between BL and malaria transmission remained when analysed using newer definitions of malaria transmission intensity and higher resolution maps than previously available.

Retrospective chart review and prospective study

665 Paediatric lymphoma cases (0-15years)

  

• Incidence rates varied by malaria transmission intensity in the different regions.

• A positive trend between BL incidence rates and malaria transmission intensity was observed, supporting an etiologic role of malaria in BL oncogenesis.

• In a log-linear model, BL rates were 3.5 times greater in regions with chronic and intense malaria transmission intensity than in regions with no or sporadic malaria transmission (OR = 3.47, 95% CI = 1.30–9.30), regardless of tribe.

Infection (malaria)

Mwanda et al. 2004 [29]

Kenya (1988-1997)

To show the geographical (Provincial), age, gender and ethnic distribution of Burkitt's lymphoma in patients in Kenya.

Retrospective records review and prospective evaluation of patients

961Children with (0-14 years)

40

60

• The disease distribution is consistent with intermediate risk Burkitt's lymphoma level.

• Furthermore the distribution varied by province, tribe, age and gender.

• The variations could be due to environmental factors.

Environmental factors

Demographic factors

Makata et al. 1996 [56]

Kenya (1979-1994).

To review histologically the paediatric solid malignant tumours in western Kenya, with a focus on the following specific objectives: to examine tumours incidence, age, sex, geographic, and ethnic distribution and to relate the tumours to putative environmental or genetic causative factors

Retrospective study

600 Children with cancer (0-14years)

38

62

• Significantly high crude incidence rates for lymphomas and Kaposi's sarcoma showed a characteristic ethnogeographic distribution.

• The majority of the tumors were found concentrated around Lake Victoria and showed decreasing occurrence as one moved towards the semi-arid and highland areas.

• Lymphomas and Kaposi Sarcoma were most significant in humid and hot areas where malaria is hyperendemic.

• Environmental factors seem to play a major role in childhood tumors in western Kenya.

• BL, Non-Hodgkin Lymphoma (NHL ) and Kaposi Sarcoma (KS) had a high incidence in the Luo tribe as compared to other tribes in the same area.

• Incidence was high in the 5-9-year age range (0.8/100,000/year)

• Retinoblastoma and nephroblastoma occurred during early childhood (0-4years) and had a possibility of being hereditary.

• BL incidence decreased with age whilst NHL and Hodgkin’s disease increased with age

Age

Tribe

Environmental factors

Genetic factors

Newton et al. 2001 [59]

Uganda (From march 1995 to February 1999)

To examine the association between HIV infection and various cancers using data from a case-control study of adults and children with cancer in Kampala, Uganda.

Case control study

128

Children with cancer and 190 children as controls (0-14 years).

40

60

• HIV infection was associated with a significantly increased risk of Kaposi’s sarcoma (OR = 94.9, 95% CI 28.5–315.3, based on 36 cases) and Burkitt’s lymphoma (OR = 7.5, 95% CI 2.8–20.1, based on 33 cases) but not with other cancers.

Infection (HIV)

(EBV)

Parkin et al. 2000 [62]

Uganda. (1994-1998).

To investigate the types of non-Hodgkin lymphoma (NHL) occurring in Kampala, Uganda, their association with Epstein-Barr virus (EBV), and how their risk is modified by HIV and other variables

Case control study

61 Children with non-Hodgkin 707 lymphoma (0-14 years)

29.2

70.8

• The vast majority of NHL cases in children were endemic BL (90%).

• 51 of the 56 BL cases were tested for the presence of EBV and all were positive

• EBV was not detected in the five cases of other lymphoma subtypes.

• The risk in endemic BL was not modified by HIV with only 5.4 % of HIV positive cases in BL.

Infection (EBV)

Ziegler and Mbidde, 1996 [63]

Uganda (1989-1994)

To report a retrospective analysis of 100 cases of KS in Ugandan children in the 6-year period

Retrospective review

100 Children with Kaposi sarcoma (0-15 years)

37

63

• The median age was 4 years.

• The incidence of childhood KS increased more than 40-fold in the era of AIDS.

• 78% of 63 cases tested were seropositive for HIV-1.

• The increase of childhood KS implies that the prevalence of causative factors is rising in Uganda.

Infection (HIV)

Aka et al. 2012 [54]

Tanzania (2000-2009)

To update baseline epidemiology of BL in northern Tanzania using recent data

Retrospective study

944 Children with BL (0-15 years)

42

58

• Tumors occurred at a younger mean age in boys than girls (6.8 years vs. 7.6 years, P < 0.01).

• Crude BL incidence varied by region (3.0 in Mwanza vs. 6.8 in Mara), by district (1.4–22), by gender (5.0 in boys vs. 4.0 in girls), and by age group (2.0 in 0–4years, 7.8 in 5–9years, and 3.1 in 10–15 years).

Age

Sex

Ethnicity

Amir et al. 2001 [14]

Tanzania (1968-1995)

To compare data on Kaposi Sarcoma in prepubescent children (0-14 years) recorded in the Tanzanian cancer registry before and during the AIDS epidemic

Retrospective chart review

150 Children with Kaposi sarcoma (0-14)

16

84

• Overall 73 (4.9/year) of these cases were registered during the pre and 77 (5.9/year) during the AIDS period.

• The highest occurrence of PKS was observed in the 0- to 5-years age group.

• The results imply that children younger than 5 years are at high risk of developing Kaposi Sarcoma.

• Possibly reflecting low resistance to human herpes virus (HHV) 8 infection.

• There is a likely hood that the increased susceptibility to HHV8 infection and morbidity is related to progressive immunodeficiency

• The increase in AIDS PKS incidence appears to reflect a direct or indirect promoting effect of HIV on the development of KS lesions.

Age

Infection (HIV and human herpes virus)

Mutalima et al. 2008 [57]

Malawi

To report risk factors for childhood BL from a case-control study conducted in Malawi focusing particular attention on three infections: HIV, EBV and malaria.

Case control study

148 children with BL and 104 controls (children admitted with non-malignant conditions other than haematological malignancies and Kaposi Sarcoma (0-15yrs).

40

60

• Reported use of mosquito nets was associated with a lower risk of BL (OR = 0.2, 95% CI, 0.03 to 0.9, p = 0.04).

• Among HIV negative participants, cases were thirteen times more likely than controls to have raised levels of EBV antibodies (OR=13.2; 95% CI 3.8 to 46.6; p = 0.001).

• Cases were more likely than controls to be HIV positive OR = 12.4, 95% CI 1.3 to 116.2, p = 0.03).

• ORs for BL increased with increasing antibody titers against EBV (p = 0.001)

Infection (EBV and malaria)

Mutalima et al. 2010 [58]

Malawi (2005-2008)

To examine the association between HIV infection and cancer among children in Blantyre, Malawi

Case control study

541 Children with cancer (0-15years)

41

59

• 97% of the children were tested for HIV and 10% were found to be seropositive for HIV.

• HIV infection was associated strongly and positively with Kaposi sarcoma (29 cases; OR = 93.5, 95% CI 26.9 to 324.4) and positively with non-Burkitt, non-Hodgkin lymphoma (33 cases; OR = 4.4, 95% CI 1.1 to 17.9).

Infection (HIV)

Sinfield et al. 2007 [61]

Malawi 1998-2003).

To document the frequency of paediatric cancers presenting to a large central hospital in Malawi, detailing the presenting features, initial investigations, and HIV status of these children. (

Retrospective study

707 Children with cancer (0-15 years)

  

• There was a significant difference in the presentation of HIV- seropositive and seronegative children in the case of BL, non-Hodgkin lymphoma, and Kaposi sarcoma.

• Kaposi sarcoma markedly increased in frequency over time.

• The proportion of children with cancer who were tested for HIV increased over time but varied by cancer type.

• Amongst those tested, the seroprevalence was 93% for children with Kaposi sarcoma, 4% (11/289) for those with BL, 31% for those with other non- Hodgkin lymphomas, 7% or those with Hodgkin disease, and 5% for those with other cancers.

Infection with HIV

Chintu et al. 1995 [55]

Zambia (1980-1992)

To study the effect of the HIV epidemic on the epidemiology of cancers in children during the pre-HIV epidemic period and after the epidemic was established.

Retrospective study

698 Children with cancer (0-14 years)

36.8

63.2

• A significant increase in the occurrence of total childhood cancers was found.

• This was mostly due to a highly significant increase in the incidence of paediatric Kaposi's sarcoma (p = 0.000016), which is causally related to HIV infection.

• A prospective in-depth epidemiological study of HIV related childhood cancers in Africa is urgently needed.

Infection (HIV)