AIDS-Related Malignancies

The onset of the acquired immunodeficiency syndrome (AIDS) epidemic was heralded by an increased incidence of a rare malignancy, Kaposi's sarcoma (KS), in 1981. Since then, scientists have recognized that individuals with AIDS have an increased risk of developing several malignancies, including KS, AIDS-related lymphoma (ARL), and invasive cervical cancer.

Both KS and invasive cervical cancer are malignancies associated with viral infection: human herpesvi-rus-8 (HHV-8) and human papillomavirus (HPV), respectively. Additionally, almost half of all cases of AIDS-related lymphomas are associated with HHV-8 or Epstein Barr virus (EBV).

KS is the most common neoplasm arising in HIV-infected individuals. Skin lesions on the lower extremities, face, and genitalia are characteristic of KS. Early lesions (patch stage) may evolve into more advanced lesions (plaque stage) as the KS tumor cells proliferate and involve more of the dermis. These lesions may eventually become ulcerating tumors (nodular stage). As compared to KS found in other epidemiologic groups (endemic-KS, iatrogenic-KS, and classic-KS) subsequent metastasis is common in AIDS-KS, with frequent sites including the oral cavity, gastrointestinal tract, and lungs. Lymphedema, particularly in the face, genitalia, and lower extremities, may be extensive.

ARLs are a heterogeneous group of tumors largely of B-cell derivation. The development of ARL generally correlates with a low CD4+ T-cell count, high HIV viral load, increased age and male gender. There are differences between the lymphomas associated with AIDS and those seen in the general population. ARL are often more advanced and severe; have involvement in areas outside of lymph nodes including the bone marrow, body cavities, jaw and soft tissues; and are associated with HHV-8 and EBV infection.

While the prevalence of oral, anal and cervical HPV infections is increased in HIV positive individuals, as is the incidence of invasive cervical cancer, the development of cancer is not correlated with a decreased CD4 T-cell count. Therefore, unlike in the cases of KS and ARL, antiretroviral therapy (ARV) therapy has not decreased the incidence of HPV-associated tumors. As cervical cancer is the second most common female cancer worldwide, and as more women are becoming infected with HIV, increased screening for cervical cancer is indicated in HIV-positive women.

There are disparities in the morbidity and mortality of AIDS-related malignancies between the developed and developing world. Since the introduction of ARV, KS incidence in HIV-positive individuals has decreased in developed nations. Similarly, decreased incidence of certain ARLs is seen in those treated with ARVs. In contrast, in the developing world, where there is high HIV prevalence and little access to ARVs, the disease burden associated with AIDS-related malignancies remains high. For example, patients in sub-Saharan Africa with AIDS-related KS have high tumor burdens and rapid disease progression resulting in a life expectancy of fewer than 6 months. In summary, HIV infection is associated with increased incidence of several malignancies that have significant morbidity and mortality, thus making the screening for and treatment of these cancers an important part of HIV management.