HIV-positive children and adolescents with a high Epstein-Barr viral load, are at greatest risk of developing an AIDS-related cancer, according to a study published on the May 14 th edition of the Journal of the American Medical Association. However, investigators add that this finding is not sufficient to explain cancer risk in HIV-positive children and that larger studies are needed.
Although malignancies have been seen less often in HIV-positive children and adolescents than in adults, HIV-positive children develop more cancers than their HIV-negative peers. It is thought that the different rates of cancers seen in HIV-infected adults and children may be explained by different modes of HIV transmission, age related factors, and coinfection with other viral infections, such as Epstein-Barr virus (RBV), cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6). However, the specific clinical, immunological and viral factors involved in an increased risk of paediatric HIV cancers has not been identified.
Accordingly, investigators involved in the Pediatric (sic) Oncology Group conducted a study involving 26 US sites treating children with HIV between 1992 and 1998. A total of 43 cases were recruited to the study, and these were matched with 73 HIV-positive cancer free controls.
Investigators obtained background demographic data, information on mode of HIV-transmission (from mother or blood products), CD4 cell count and HIV viral loads, history of past AIDS-related illnesses, use of AZT, and coinfection with other chronic viruses including EBV, CMV and HHV-6. This was then analysed to establish if any cancer risks could be identified.
Over 75% of the cancers seen in the children were lymphoid malignancies, with non-Hogkins lymphoma the most common.
Risk factors
Cases were slightly younger than controls (average age 7.3 years versus 9.5), however similar proportions of cases and controls were vertically infected with HIV (55.8% versus 60.8%). The average duration of HIV infection in the children with cancer was 4.8 years against 5.7 years for the controls.
CD4 cell counts were significantly lower in cases at an average of 124 cells/mm3 versus 337 cells/mm3 in the controls. AZT use by the child or either parent was not associated with an increased risk of cancer.
HIV viral loads did not differ significantly between cases or controls, but EBV viral loads were substantially higher in children with cancer than those without. However there was no significant difference in either CMV or HHV-6 viral loads.
Past experience of HIV-related disease was almost identical between the cases and controls and similar proportions had received routine childhood vaccinations.
When the association between low CD4 cell count and high EBV viral load was further analysed, investigators found that “high EBV viral loads were strongly associated with cancer risk but only for children with CD4 cell counts of at least 200 cells/mm3; there was more than an 11-fold increased risk of cancer in children with high EBV viral load and high CD4 cell counts.” The investigators add, “in contrast, there was no association between EBV and cancer risk for children with CD4 cell counts lower than 200 cells/mm3.”
No other significant risk factors were found.
The investigators comment, “this is the first reported case-controlled study designed to identify clinical and molecular risk factors for pediatric (sic) HIV-related malignancies." Noting the apparent role for EBV, they comment that this “cannot provide the sole explanation for the increased risk of cancer. Indeed, in our HIV-infected study population, increased EBV burden alone does not appear to be a sufficient cause of malignancy given that the risk was not independently increased in children with low CD4 cell counts.” However the study was not able to determine any other independent risk factors. They suggest that an international prospective study “would allow for assessment of the temporal inter-retionships between EBV replication, viral load and immune function.”
Further information on this website
Cancers - overview
Pollock BH et al. Risk factors for pediatric human immunodeficiency virus-related malignancy Journal of the American Medical Association, 289: 2393 – 2399, 2003.