The human immunodeficiency virus (HIV) is associated with more cancers than any other human virus. This retrovirus is not the direct cause, but its suppression of immune system function leads to the development of several human malignancies, particularly those linked to a virus infection. Certain of these cancers initially designated the diagnosis of AIDS: Kaposi Sarcoma (KS), non-Hodgkin's lymphoma(NHL), and invasive cervical carcinoma. These AIDS-defining malignancies are associated with herpesviruses (KHSV and EBV) and papillomaviruses(HPV).
HIV exists in two types, HIV-1 and HIV-2. Its diversity is appreciated by its genomic and biologic properties, having isolates that infect, to varying extents, a large variety of human cells. HIV replication involves reverse transcription from an RNA genome into a double-stranded DNA copy that integrates into the cellular chromosome. The virus is then retained by the infected individual in cellular reservoirs and can continue to compromise the immune system. Moreover cytokines, released by cells infected by viruses, the microenvironment or the immune system, can enhance tumor cell proliferation and survival. Thus, a balance between pro-inflammatory and anti-inflammatory responses can play a role in HIV-associated cancers.
Another retrovirus, the human T cell leukemia or T-lymphotropic virus (HTLV), was the first human retrovirus found as an etiologic agent in a malignancy. It exists primarily as two types, HTLV-1 and HTLV-2. This virus is the cause of T-cell malignancies, particularly adult T cell leukemia/lymphoma, that also has an increased prevalence in HIV infection. The glucose transport-1 protein is most likely the cellular receptor for HTLV-1 and the Tax protein is linked to the transformation of cells leading to tumor development. Chemotherapy can reduce the tumor mass but long-term survival is rare.
The Epstein Barr virus (EBV), a herpesvirus, was the first human cancer virus identified. It was initially detected in Burkitt's lymphoma, and later in nasopharyneal carcinomas and Hodgkin's lymphoma. With HIV infection, besides NHL, EBV is found in B cell lymphomas of the brain. Other B cell lymphomas occur in AIDS for which a viral agent has not been identified. More recently, EBV has been detected in a variety of other human cancers, not necessarily linked to HIV, including NK/T cell lymphoma, gastric carcinoma and smooth muscle tumors. The pathogenesis of EBV infection involves an interaction with its cell surface receptor CD21 or sometimes CD3 on B cells and epithelial cells that mediate the establishment of the infection. Cell transformation can involve the viral proteins, EBNA and LMR. Currently, a vaccine against EBV is being pursued and certain drugs, such as ganciclovir, have been helpful against the virus.
Over the years, other malignancies, mostly virus-induced, have been recognized in HIV-infected individuals. These include cancers linked to herpesviruses, polyomaviruses and papilloma viruses as well as those associated with Hepatitis B virus and Hepatitis C virus infections. The mechanisms for the induction of the cell transformation involved differ for each of the malignancies and their emergence can reflect either an immune-deficient or an immune-enhanced clinical state. Whether other cancers associated with HIV infection including melanoma, non EBV-associated B cell lymphomas, and unusual hematopoietic cancers are also caused by a virus await further investigation. This AACR conference will explore the various viruses associated with human malignancies and discuss their pathogenesis, oncogenic potential, and treatment.
Citation Format: Jay A. Levy. HIV, HTLV, and EBV infection and the development of cancer [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr IA36.