The relationship between malignancies and AIDS began changing in 1996 (1,2) when the highly active antiretroviral (HAART) therapy regimens were introduced in the industrial nations. Thanks to the United Nations efforts and to general programs of economic support and philanthropy, HAART has also been successfully introduced into a significant number of developing nations. Africa, the main epicenter of the pandemic, has been the exception, due to the sheer magnitude of the African epidemic. Significant political and social turmoil has hampered the efficiency of these efforts in Africa (3). Prior to 1996, epidemiologists noted that specific malignancies afflicted patients with AIDS, and that the risk of development of a malignancy was directly proportional to the degree of immunodeficiency of the infected host. Before the development of HAART, patients with AIDS could be separated into two groups: patients who would have an opportunistic infection as their first manifestation of AIDS (60%) and those who would have a malignancy as the mode of presentation (40%) (4).
Of those with an AIDS-related malignancy, up to 90% would have Kaposi sarcoma (KS) and the rest had non-Hodgkin lymphomas (NHL), including primary central nervous system lymphoma (PCNSL) and systemic diffuse large B-cell lymphoma (DLBCL). While there was, and continues to be, an increase in HPV-related invasive cervical cancers, particularly in women with high-grade uterine cervical dysplasias, recent findings of a lack of a clear association between the occurrence of cervical cancer and the degree of HIV-related immunosuppression has created questions about the validity of including cervical cancer among the AIDS-defining or associated malignancies (5). Epithelial dysplasia and squamous cell carcinomas of the anal canal, rectum, and oral cavity are also observed in men infected by HIV (human immunodeficiency virus). After the introduction of HAART, these previously obvious relationships between AIDS and AIDS-related malignancies have been significantly challenged. This has been most clearly observed with HIV-related Burkitt lymphoma, a NHL initially associated with the AIDS-induced immunosuppression. Investigators studying the incidence of HIV-related Burkitt lymphoma before and after introduction of HAART have found that although the improvement in immunity due to the administration of HAART has been associated with significant reductions in KS, PCNSL, and systemic DLBCL, the same is not true with Burkitt lymphoma, once considered a typical AIDS-defining malignancy (6). As in the case with invasive cervical cancer, the incidence of Burkitt lymphoma has remained stable between the pre-HAART and the post-HAART eras, thereby increasing its proportional frequency. In addition to these observations, there has been in the post-HAART era an increase in Hodgkin lymphoma (Epstein-Barr virus related), lung cancer, and non-melanoma skin cancer, which carries significant etiologic implications related to the complex relationship between immunity, aging, chronic antigenic stimulation, and viral oncogenesis. Overall, the excess risk of a malignancy in HIV disease has been observed, before and after HAART introduction, mostly in cancers with an established or suspected infectious cause (7).