HIV infection and malignancy: Epidemiology and pathogenesis
- John F Deeken, MD
John F Deeken, MD
- Associate Professor
- Virginia Commonwealth University
- Associate Director for Medical Oncology and Clinical Research
- Inova Comprehensive Cancer and Research Institute
- Liron Pantanowitz, MD
Liron Pantanowitz, MD
- Associate Professor of Pathology
- University of Pittsburgh Medical Center
HIV-infected individuals have an increased propensity to develop malignancy [1,2]. The occurrence of an extremely high number of cases of Kaposi's sarcoma (KS) was noted early in the AIDS epidemic and many of them had an unusually aggressive clinical course. KS was therefore included as an AIDS-defining illness in early case definitions from the Centers for Disease Control and Prevention (CDC). Non-Hodgkin lymphoma (NHL) and invasive cervical carcinoma were subsequently added as AIDS-defining conditions.
The spectrum of neoplasia in HIV infected patients has changed in areas where the use of potent antiretroviral therapy (ART) is widespread. The incidence of KS and NHL has decreased markedly, but there has been a relative increase in tumor types that collectively are referred to as non-AIDS-defining cancers (NADCs) compared with the general population. NADCs now are a major factor contributing to mortality in HIV-infected people.
This topic will review the epidemiology and pathogenesis of malignancy in people infected with HIV. General management considerations for these malignancies, as well as epidemiologic features and management considerations for specific tumor types are discussed separately. (See "HIV infection and malignancy: Management considerations".)
The era of potent ART began in 1996 with the availability of the protease inhibitors. In most patients, ART causes both an immunologic response manifested by normalization CD4 lymphocyte counts and a virologic response with nearly complete suppression of HIV viral replication. Both immunologic and virologic responses are important in achieving at least partial immune restoration, thus decreasing the incidence of opportunistic infections, reducing the risk of developing NHL or KS, and prolonging survival [3-5]. (See "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient".)
AIDS-defining malignancies — The overall impact of the introduction of ART is illustrated by the Swiss HIV Cohort Study, which analyzed the incidence of AIDS-defining and non-AIDS defining cancers in 9429 patients with 54,715 years of patient follow-up . The incidence of cancers was broken down into three periods: 1985 to 1996 (pre-ART), 1997 to 2001 (early ART), and 2002 to 2006 (late ART).To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Rubinstein PG, Aboulafia DM, Zloza A. Malignancies in HIV/AIDS: from epidemiology to therapeutic challenges. AIDS 2014; 28:453.
- Carbone A, Vaccher E, Gloghini A, et al. Diagnosis and management of lymphomas and other cancers in HIV-infected patients. Nat Rev Clin Oncol 2014; 11:223.
- Grabar S, Le Moing V, Goujard C, et al. Clinical outcome of patients with HIV-1 infection according to immunologic and virologic response after 6 months of highly active antiretroviral therapy. Ann Intern Med 2000; 133:401.
- Bonnet F, Balestre E, Thiébaut R, et al. Factors associated with the occurrence of AIDS-related non-Hodgkin lymphoma in the era of highly active antiretroviral therapy: Aquitaine Cohort, France. Clin Infect Dis 2006; 42:411.
- Shiels MS, Engels EA. Evolving epidemiology of HIV-associated malignancies. Curr Opin HIV AIDS 2017; 12:6.
- Franceschi S, Lise M, Clifford GM, et al. Changing patterns of cancer incidence in the early- and late-HAART periods: the Swiss HIV Cohort Study. Br J Cancer 2010; 103:416.
- Powles T, Robinson D, Stebbing J, et al. Highly active antiretroviral therapy and the incidence of non-AIDS-defining cancers in people with HIV infection. J Clin Oncol 2009; 27:884.
- Patel P, Hanson DL, Sullivan PS, et al. Incidence of types of cancer among HIV-infected persons compared with the general population in the United States, 1992-2003. Ann Intern Med 2008; 148:728.
- Shiels MS, Pfeiffer RM, Gail MH, et al. Cancer burden in the HIV-infected population in the United States. J Natl Cancer Inst 2011; 103:753.
- Herida M, Mary-Krause M, Kaphan R, et al. Incidence of non-AIDS-defining cancers before and during the highly active antiretroviral therapy era in a cohort of human immunodeficiency virus-infected patients. J Clin Oncol 2003; 21:3447.
- Deeken JF, Tjen-A-Looi A, Rudek MA, et al. The rising challenge of non-AIDS-defining cancers in HIV-infected patients. Clin Infect Dis 2012; 55:1228.
- Biggar RJ, Chaturvedi AK, Goedert JJ, et al. AIDS-related cancer and severity of immunosuppression in persons with AIDS. J Natl Cancer Inst 2007; 99:962.
- Stein M, O'Sullivan P, Wachtel T, et al. Causes of death in persons with human immunodeficiency virus infection. Am J Med 1992; 93:387.
- Kravcik S, Hawley-Foss N, Victor G, et al. Causes of death of HIV-infected persons in Ottawa, Ontario, 1984-1995. Arch Intern Med 1997; 157:2069.
- Bonnet F, Lewden C, May T, et al. Malignancy-related causes of death in human immunodeficiency virus-infected patients in the era of highly active antiretroviral therapy. Cancer 2004; 101:317.
- Grulich AE, van Leeuwen MT, Falster MO, Vajdic CM. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet 2007; 370:59.
- Singh E, Naidu G, Davies MA, Bohlius J. HIV-associated malignancies in children. Curr Opin HIV AIDS 2017; 12:77.
- Simard EP, Shiels MS, Bhatia K, Engels EA. Long-term cancer risk among people diagnosed with AIDS during childhood. Cancer Epidemiol Biomarkers Prev 2012; 21:148.
- Carbone A, Gloghini A. AIDS-related lymphomas: from pathogenesis to pathology. Br J Haematol 2005; 130:662.
- Shiels MS, Althoff KN, Pfeiffer RM, et al. HIV Infection, Immunosuppression, and Age at Diagnosis of Non-AIDS-Defining Cancers. Clin Infect Dis 2017; 64:468.
- Frisch M, Biggar RJ, Goedert JJ. Human papillomavirus-associated cancers in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. J Natl Cancer Inst 2000; 92:1500.
- Beachler DC, Abraham AG, Silverberg MJ, et al. Incidence and risk factors of HPV-related and HPV-unrelated Head and Neck Squamous Cell Carcinoma in HIV-infected individuals. Oral Oncol 2014; 50:1169.
- Mailankody S, Landgren O. HIV, EBV, and monoclonal gammopathy. Blood 2013; 122:2924.
- Ouedraogo DE, Makinson A, Vendrell JP, et al. Pivotal role of HIV and EBV replication in the long-term persistence of monoclonal gammopathy in patients on antiretroviral therapy. Blood 2013; 122:3030.
- Purgina B, Rao UN, Miettinen M, Pantanowitz L. AIDS-Related EBV-Associated Smooth Muscle Tumors: A Review of 64 Published Cases. Patholog Res Int 2011; 2011:561548.
- Xu S, Jiang J, Yu X, et al. Association of Merkel cell polyomavirus infection with EGFR mutation status in Chinese non-small cell lung cancer patients. Lung Cancer 2014; 83:341.
- Lasithiotaki I, Antoniou KM, Derdas SP, et al. The presence of Merkel cell polyomavirus is associated with deregulated expression of BRAF and Bcl-2 genes in non-small cell lung cancer. Int J Cancer 2013; 133:604.
- Colombara DV, Manhart LE, Carter JJ, et al. Prior human polyomavirus and papillomavirus infection and incident lung cancer: a nested case-control study. Cancer Causes Control 2015; 26:1835.
- Karimi S, Yousefi F, Seifi S, et al. No evidence for a role of Merkel cell polyomavirus in small cell lung cancer among Iranian subjects. Pathol Res Pract 2014; 210:836.
- Muehlenbachs A, Bhatnagar J, Agudelo CA, et al. Malignant Transformation of Hymenolepis nana in a Human Host. N Engl J Med 2015; 373:1845.
- Kirk GD, Merlo C, O' Driscoll P, et al. HIV infection is associated with an increased risk for lung cancer, independent of smoking. Clin Infect Dis 2007; 45:103.
- Silverberg MJ, Lau B, Achenbach CJ, et al. Cumulative Incidence of Cancer Among Persons With HIV in North America: A Cohort Study. Ann Intern Med 2015; 163:507.
- Yanik EL, Napravnik S, Cole SR, et al. Incidence and timing of cancer in HIV-infected individuals following initiation of combination antiretroviral therapy. Clin Infect Dis 2013; 57:756.
- AIDS-defining malignancies
- Non-AIDS-defining cancers
- HIV infection diagnosed during childhood
- Role of the HIV virus
- Coinfection with oncogenic organisms
- - HHV-8 infection
- - HPV infection
- - EBV infection
- - HBV and HCV infection
- - Merkel cell polyoma virus
- - Hymenolepis nana
- - Other environmental oncogenic stimuli
- Antiretroviral drugs and timing of cancer development