AIDS-associated malignancy represents a model system for investigations of carcinogenesis. There are few human conditions in which cancer rates are of the magnitude as in HIV infection, in which the absolute risk of developing a malignancy exceeds 10% within the first 10 years. HIV infection is known to increase the incidence of at least 23 malignancies, non-Hodgkin's lymphoma (NHL) and Kaposi's sarcoma (KS). These tumors differ in their patterns of incidence: lymphoma incidence increases with duration of HIV infection whereas Kaposi's sarcoma incidence is elevated in certain demographic and geographic groups. This contrast implies that HIV may induce cancer by varying mechanisms perhaps Kaposi's sarcoma by interaction with a co-factor, such as the human herpes virus 8 (HHV-8), and lymphoma via immune perturbation. Therapy for HIV and opportunistic infections has increased the survival of HIV-infected patients. The long-term consequences of such therapy or of prolonged survival remain undefined. Alteration of cancer risk is of particular concern, as cancer may be expected to increase in importance as opportunistic infections yield to advances in therapy. HIV- associated cancers have already emerged as a leading cause of death among patients with AIDS. This large prospective cohort study will establish a collection of tumors linked with pre-cancer sera and lymphocytes with which candidate assays, as they are developed, can be validated and correlated to malignancy outcomes. The materials and data collected will be utilized to determine the etiologic mechanisms of cancer development, with a particular focus on elucidating the pathogenesis of oncogenic infectious agents and identifying pre-clinical markers of malignant transformation. Predictors of malignancy development will be sought, particularly with regard to the development of these cancers. Other potential etiologic mechanisms of carcinogenesis including the presence of specific lymphoma-associated translocations in pre-cancer peripheral blood, cytokine and lymphokine activation, antiretroviral exposure and chemical carcinogen exposure, will also be investigated.
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