Context Although cancers occur with increased frequency in children with human
immunodeficiency virus (HIV) infection, the specific clinical, immunological,
and viral risk factors for malignancy have not been identified.
Objective To identify risk factors for malignancy among HIV-infected children.
Design, Setting, and Patients A multicenter case-control study of children with HIV at 26 institutions
participating in the Pediatric Oncology Group. Forty-three case patients with
a new malignancy and 74 control patients without a malignancy were matched
based on the duration of their infection. Patients were enrolled between January
1992 and July 1998.
Main Outcome Measures Clinical and laboratory factors assessed as putative risk factors included
demographic characteristics, HIV characteristics, prior antiretroviral treatment,
and CD4 cell count. Coviral infections with Epstein-Barr virus (EBV), cytomegalovirus,
and human herpesvirus 6 were assessed by semiquantitative polymerase chain
reaction assays and serological testing.
Results Case malignancy diagnoses included 28 non-Hodgkin lymphoma, 4 B-cell
acute lymphoblastic leukemia, 1 Hodgkin disease, 8 leiomyosarcoma, 1 hepatoblastoma,
and 1 schwannoma. Epstein-Barr virus viral load of more than 50 viral genome
copies per 105 peripheral blood mononuclear cells was strongly
associated with cancer risk but only for children with CD4 cell counts of
at least 200/µL (odds ratio [OR], 11.33; 95% confidence interval [CI],
2.09-65.66, P<.001). High EBV viral load was not
associated with cancer for children with CD4 cell counts of less than 200/µL
(OR, 1.12; 95% CI, 0.13-9.62; P = .99). Zidovudine
antiretroviral therapy did not confer a significant protective effect for
either the high (OR, 0.81; 95% CI, 0.22-3.09; P =
.77) or the low CD4 cell count groups (OR, 0.27; 95% CI, 0.04-1.46; P = .16). The route of HIV infection was not associated
with increased cancer risk.
Conclusions Route of infection, demographic characteristics, and zidovudine use
were not associated with the development of malignancy in HIV-infected children.
High viral burden with EBV was associated with the development of malignancy
in HIV-infected children although the effect was modified by CD4 cell count.
The pathogenesis of HIV-related pediatric malignancies remains unclear and
other contributing risk factors can be elucidated only through further study.