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Cancer Risk Remains High for People Who Had AIDS as a Child
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18th Conference on Retroviruses and Opportunistic Infections, February 27-March 2, 2011, Boston
Mark Mascolini
Although incidence of two AIDS cancers has dropped sharply in US teens and young adults diagnosed with AIDS in childhood, young people in the current antiretroviral era remain at high risk for Kaposi sarcoma and non-Hodgkin lymphoma when compared with the general population [1]. This large analysis of AIDS and cancer registries found no change in incidence (new diagnoses) of non-AIDS cancers from before 1996 through the current treatment era.
Children diagnosed with AIDS have survived into adolescence and young adulthood thanks to combination antiretroviral therapy (cART). But cART does not fully restore the immune system, so these young people may remain at high risk for AIDS cancers and non-AIDS cancers. Data from cancer incidence studies in HIV-positive adults cannot be applied to children, adolescents, and young adults because younger people have different cancer risk factors.
Researchers from the National Cancer Institute (NCI) and Columbia University planned this study to compare cancer risk in HIV-positive young people and the general population, looking for changes from the pre-cART era (1980 to 1995) to the cART era (1996 to 2008). They assessed cancer incidence in children diagnosed with AIDS before the age of 15 (from 1980 to 2007), focusing on a period beginning 60 months before AIDS diagnosis to 120 months after diagnosis. Follow-up continued until month 120, death, or the end of cancer registry coverage. Data came from AIDS registries in 15 US regions, which were matched to cancer registry data.
The study group included 5846 people who were under 15 years old at AIDS diagnosis, divided into 4236 in the pre-cART era and 1610 in the cART era. Both groups were almost evenly split between boys and girls. Most children in the pre-cART group (59.8%) and the cART group (66.8%) were black. Age at AIDS diagnosis was 4 years or under in 71.6% in the pre-cART group and 48.1% in the cART group. The cART group had a higher proportion of children diagnosed with AIDS at 10 to 14 years of age, 31.1% versus 11.4% in the pre-cART group.
Considering all malignancies, the researchers determined that cancer was 40 times more frequent with HIV than in the general population in the pre-cART era (standardized incidence ratio [SIR] 40, 95% confidence interval [CI] 32 to 51). In the cART era, all cancers combined were 17 times more frequent with HIV than in the general population (SIR 17, 95% CI 12 to 23). People with AIDS in childhood had a 1688-fold higher risk of Kaposi sarcoma in pre-CART years and a 1087-fold higher risk in the cART era. The heightened risk for non-Hodgkin lymphoma with HIV fell from 336-fold in the pre-cART era to 116-fold in the cART era. There were no cases of cervical cancer, the third AIDS-defining cancer.
The NCI-Columbia team counted 8 cases of non-AIDS cancer in the pre-cART era and 11 in the cART era. Overall risk for these cancers did not change from one era to the next: SIR 5 (95% CI 2 to 10) in the preCART era, SIR 6 (95% CI 3 to 10) in the cART era. Leiomyosarcoma, a smooth muscle malignancy, was the most common non-AIDS cancer, diagnosed in 4 people. The risk for HIV-positive people was 863-fold higher in the pre-cART era and 531-fold higher in the cART era. The other non-AIDS cancers were 2 soft-tissue malignancies, 1 liver cancer, and 1 thyroid cancer, with the other cancers poorly defined.
Comparing cancer incidence in the pre-cART and cART eras only in the HIV-positive group, the researchers determined that the incidence of all cancers together fell almost 60% (rate ratio [RR] 0.38, 95% CI 0.23 to 0.64), the incidence of Kaposi sarcoma dropped more than 85% (RR 0.13, 95% CI 0.02 to 0.74), and the incidence of non-Hodgkin lymphoma fell 60% (RR 0.40, 95% CI 0.11 to 0.75). Of the two most frequent non-AIDS cancers, leiomyosarcoma and soft tissue malignancies, incidence of neither fell significantly from pre-cART days to the cART era.
The investigators noted one limitation of their analysis--lack of individual data on immune suppression, presence of oncogenic viruses, and antiretroviral therapy. Strengths of this study, the researchers proposed, are the large sample size, extended observation into the current antiretroviral era, and access to detailed cancer information.
The researchers concluded that people diagnosed with AIDS during childhood remain at an elevated risk for Kaposi sarcoma, non-Hodgkin lymphoma, soft tissue cancers, and leiomyosarcoma when compared with the general population. Two thirds of the observed cancers--the cases of non-Hodgkin lymphoma and leiomyosarcoma--are linked to Epstein-Barr virus. Although incidence of AIDS cancers dropped sharply after the arrival of combination antiretroviral therapy, incidence of non-AIDS cancers has not declined.
"As children with AIDS age into adulthood," the research team advised, "long-term monitoring will be important [because] their cancer risk factors will likely change."
Reference
1. Simard E, Shiels M, Bhatia K, Engels E. Long-term cancer risk among people diagnosed with AIDS during childhood. 18th Conference on Retroviruses and Opportunistic Infections. February 27-March 2, 2011. Boston. Abstract 82LB.
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