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Epidemiology and Natural History of Cancer-Associated Viruses

Sam Mbulaiteye

1 Collaborator(s)

Funding source

National Cancer Institute (NIH)
This project consists of several overlapping comprehensive, multidisciplinary population-based cohort and/or case-control studies to quantify the association between cancer-causing viruses (oncoviruses) with linked cancers. The studies focus on the role of the role of immunological alteration, infection and risk for cancer, including BL, NHL, Hodgkin lymphoma, kaposi sarcoma, lung cancer, cervical cancer, head and neck cancer, testicular cancer, breast cancer, penile cancer, and gastric cancer. Biological specimens (peripheral blood, saliva, tumor tissues), when available, are used to measure load of infectious agents, including HIV, HTLV-I/-II, HCV, and KSHV, also called HHV8, genetic variation in viral agents or the host to characterize association of biomarkers with cancer. An analysis of risk for AIDS and non-AIDS-defining cancers in the U.S. covering a 15-year period (1991-2005) was completed. The US AIDS population expanded fourfold from 96,179 in 1991 to 413,080 in 2005. The increases were mostly due to people aged 40 years or older. About 79 656 cancers occurred in the AIDS population. The number of AIDS-defining cancers decreased by more than threefold from 34,587 in 1991 to 10,325 cancers in 2005; Ptrend .001). Conversely, during the same time, the number of non-AIDS-defining cancers increased by approximately threefold (3193 to 10,059 cancers; Ptrend .001). The number of cancers for anus (206 to 1564 cancers), liver (116 to 583 cancers), prostate (87 to 759 cancers), and lung cancers (875 to 1882 cancers), and Hodgkin lymphoma (426 to 897 cancers). In the HIV-only population in 34 US states, an estimated 2191 non-AIDS-defining cancers occurred during 2004-2007, including 454 lung, 166 breast, and 154 anal cancers. This growing burden requires targeted cancer prevention and treatment strategies Using the U.S. HIV/AIDS Cancer Match Study, among 567, 865 persons with HIV/AIDS, BL incidence showed two age-specific incidence peaks during the pediatric and adult/geriatric years and decreased with decreasing CD4 lymphocyte counts. The bimodal peaks for BL, in contrast to non-BL NHL, suggest effects of non-cumulative risk factors at different ages. An analysis of the proportion of AIDS-defining malignancies in the United States occurring in persons with AIDS during 1980-2007 was completed. About 82% of 83,252 KS cases, 6.0% of 351,618 DLBCL cases, 20% of 17,307 Burkitt lymphoma cases, 27% of 27,265 CNS lymphoma cases, and 0.42% of 375,452 cervical cancer cases occurred among persons with AIDS during 1980-2007. The proportion of KS and AIDS-defining NHLs in persons with AIDS peaked in the early 1990s (1990-1995: 90% for KS, 10% for DLBCL, 28% for Burkitt lymphoma and 48% for CNS lymphoma and then declined 70% for KS, 5% for DLBCL,21% for BL, and 13% for CNS lymphoma. The proportion of cervical cancers in persons with AIDS increased over time from 0.11% in 1980-1991 to 0.71% in 2001-2007. Prostate cancer risk was decreased by 50% among men with AIDS compared with the general population. This deficit was limited to the PSA era and early stage cancers. A study of Hodgkin lymphoma (HL) incidence with immune reconstitution in the HIV settng was completed using data on 187 Hodgkin lymphoma cases among 64 368 HIV patients from France. Hodgkin lymphoma risk was related to time intervals after combination antiretroviral therapy (cART) initiation. Risk was especially and significantly elevated in months 1-3 on cART (RR 2.95), lower in months 4-6 (RR 1.63), and null with longer use (RR 1.00). CD4 count was strongly associated with Hodgkin lymphoma risk at 50-99 CD4 cells/mm. Hodgkin lymphoma risk increased significantly soon after cART initiation, which was largely explained by the CD4 count. Using data from 263 254 adults and adolescents with AIDS (1980-2004) the U.S. HACM, we showed that risk was elevated for the 2 major AIDS-defining cancers: Kaposi sarcoma (SIRs, 5321 and 1347 in years 3-5 and 6-10, respectively) and non-Hodgkin ...