Human retroviruses: Their role in cancer

Viruses are etiologically linked to approximately 20% of all malignancies w orldwide. Retroviruses account for approximately 8%-10% of the total. For h uman T-cell leukemia virus 1 (HTLV-1), the viral regulatory tax gene produc t is responsible for enhanced transcription of viral and cellular genes tha t promote cell growth by stimulating Various growth factors and through dys regulation of cellular regulatory suppressor genes, such as p53. After a lo ng latent period, adult T-cell leukemia/lymphoma (ATL) occurs in 1 per 1000 carriers per year, resulting in 2500-3000 cases per year worldwide and ove r half of the adult lymphoid malignancies in endemic areas. Human immunodef iciency virus 1 (HIV-1) accounts for a significant cancer burden, and its t ransactivating regulatory protein Tat enhances direct and indirect cytokine and immunological dysregulation to cause diverse cancers. Kaposi's sarcoma (KS) is a very rare tumor except after HIV-1 infection, when its incidence is greatly amplified reaching seventy thousand-fold in HIV-infected homose xual men. Human herpesvirus 8 (HHV-8), which is also known as Kaposi's sarc oma-associated virus (KSHV), is a necessary but not sufficient etiological factor in KS. The dramatic decline of KS since the introduction of highly a ctive antiretroviral therapy (HAART) could be due to suppression of HIV-1 t at. B-cell non-Hodgkin's lymphoma occurs as their first acquired immunodefi ciency syndrome-defining diagnosis in 3%-4% of HIV-infected patients. Hodgk in's lymphoma is also associated with HIV infection but at a lower risk. Hu man papillomaviruses are linked to invasive cervical cancer and anogenital cancers among HIV-infected patients. Human retroviruses cause malignancy vi a direct effects as well as through interactions with other oncogenic herpe sviruses and other viruses.