Cancer in the HIV-Infected Host: Epidemiology and Pathogenesis in the Antiretroviral Era
- 749 Downloads
- 16 Citations
Abstract
Cancer and HIV are inextricably linked. Although the advent of antiretroviral therapy has led to a marked decline in the incidence of malignancies classically linked to immunosuppression (AIDS-defining malignancies, or ADMs), this decrease has been accompanied by a concomitant rise in the incidence of other malignancies (non-AIDS-defining malignancies, or NADMs). Population-based cancer registries provide key information about cancer epidemiology in people living with HIV (PLWH) within resource-rich countries. The risk for NADMs is elevated in PLWH compared with the general population, particularly for lung and anal cancers. Contributory factors include tobacco use, coinfection with oncogenic viruses such as human papillomavirus, and potentially direct effects of HIV itself. Data from resource-poor countries are limited and highlight the need for more studies in countries where the majority of PLWH reside. Strategies for early cancer detection and/or prevention are necessary in PLWH.
Keywords
Cancer HIV AIDS-defining malignancy Non-AIDS-defining malignancy Incidence Incidence trends Pathogenesis SurvivalNotes
Compliance with Ethics Guidelines
Conflict of Interest
Dr. Brickman has nothing to disclose, and Dr. Palefsky reports grants from Merck and Co., grants from Hologic, nonfinancial support and other from Vaxgenetics, other from Vical, and personal fees from Bristol-Myers Squibb, outside the submitted work.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
References
Papers of particular interest, published recently, have been highlighted as: •Of importance, •• Of major importance
- 1.Centers for Disease, C. Kaposi’s sarcoma and Pneumocystis pneumonia among homosexual men—New York City and California. MMWR Morb Mortal Wkly Rep. 1981;30(25):305–8.Google Scholar
- 2.Centers for Disease, C. Revision of the case definition of acquired immunodeficiency syndrome for national reporting—United States. MMWR Morb Mortal Wkly Rep. 1985;34(25):373–5.Google Scholar
- 3.Centers for Disease, C. and Prevention. Impact of the expanded AIDS surveillance case definition on AIDS case reporting—United States, first quarter, 1993. MMWR Morb Mortal Wkly Rep. 1993;42(16):308–10.Google Scholar
- 4.Biggar RJ et al. AIDS-related cancer and severity of immunosuppression in persons with AIDS. J Natl Cancer Inst. 2007;99(12):962–72.CrossRefPubMedGoogle Scholar
- 5.Franceschi S et al. Kaposi sarcoma incidence in the swiss HIV cohort study before and after highly active antiretroviral therapy. Br J Cancer. 2008;99(5):800–4.PubMedCentralCrossRefPubMedGoogle Scholar
- 6.Polesel J et al. Non-Hodgkin lymphoma incidence in the swiss HIV cohort study before and after highly active antiretroviral therapy. AIDS. 2008;22(2):301–6.CrossRefPubMedGoogle Scholar
- 7.•Morlat P et al. Causes of death among HIV-infected patients in France in 2010 (national survey): trends since 2000. AIDS. 2014;28(8):1181–91. Data from large French survey that summarizes causes of death in PLWH in the modern, post-ART era.CrossRefPubMedGoogle Scholar
- 8.••Robbins HA, et al. Excess cancers among HIV-infected people in the United States. J Natl Cancer Inst, 2015. 107(4). Most current HACM data on epidemiology of cancer among PLWH in the U.S. Uses SEER registry data to compares incidence of cancer among HIV-infected people to the general populationGoogle Scholar
- 9.••Robbins HA et al. Epidemiologic contributions to recent cancer trends among HIV-infected people in the United States. AIDS. 2014;28(6):881–90. HACM data to evaluate incidence of cancer among PLWH over time and to assess the effect of (i) the age distribution of PLWH (ii) changes in incidence in the general population and (iii) HIV infection iteself, on these time trends.CrossRefPubMedGoogle Scholar
- 10.••Hleyhel M et al. Risk of AIDS-defining cancers among HIV-1-infected patients in France between 1992 and 2009: results from the FHDH-ANRS CO4 cohort. Clin Infect Dis. 2013;57(11):1638–47. Updated data from the French Hospital National Database on HIV showing changes in the incidence of ADMs over time.CrossRefPubMedGoogle Scholar
- 11.••Hleyhel M et al. Risk of non-AIDS-defining cancers among HIV-1-infected individuals in France between 1997 and 2009: results from a French cohort. AIDS. 2014;28(14):2109–18. Updated data from the French Hospital National Database on HIV showing changes in the incidence of NADMs over time.CrossRefPubMedGoogle Scholar
- 12.Gopal S et al. Moving forward in HIV-associated cancer. J Clin Oncol. 2014;32(9):876–80.PubMedCentralCrossRefPubMedGoogle Scholar
- 13.Silverberg MJ et al. HIV infection and the risk of cancers with and without a known infectious cause. AIDS. 2009;23(17):2337–45.PubMedCentralCrossRefPubMedGoogle Scholar
- 14.Clifford GM et al. Cancer risk in the swiss HIV cohort study: associations with immunodeficiency, smoking, and highly active antiretroviral therapy. J Natl Cancer Inst. 2005;97(6):425–32.CrossRefPubMedGoogle Scholar
- 15.Patel P 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(10):728–36.CrossRefPubMedGoogle Scholar
- 16.van Leeuwen MT et al. Continuing declines in some but not all HIV-associated cancers in Australia after widespread use of antiretroviral therapy. AIDS. 2009;23(16):2183–90.PubMedCentralCrossRefPubMedGoogle Scholar
- 17.Franceschi S et al. Changing patterns of cancer incidence in the early- and late-HAART periods: the swiss HIV cohort study. Br J Cancer. 2010;103(3):416–22.PubMedCentralCrossRefPubMedGoogle Scholar
- 18.Shiels MS et al. Cancer burden in the HIV-infected population in the United States. J Natl Cancer Inst. 2011;103(9):753–62.PubMedCentralCrossRefPubMedGoogle Scholar
- 19.Silverberg MJ et al. HIV infection, immunodeficiency, viral replication, and the risk of cancer. Cancer Epidemiol Biomarkers Prev. 2011;20(12):2551–9.PubMedCentralCrossRefPubMedGoogle Scholar
- 20.Parkin DM. The evolution of the population-based cancer registry. Nat Rev Cancer. 2006;6(8):603–12.CrossRefPubMedGoogle Scholar
- 21.Chen M et al. Prevalence of undiagnosed HIV infection among persons aged >/=13 years—national HIV surveillance system, United States, 2005–2008. MMWR Morb Mortal Wkly Rep. 2012;61:57–64.PubMedGoogle Scholar
- 22.Cutrell J, Bedimo R. Non-AIDS-defining cancers among HIV-infected patients. Curr HIV/AIDS Rep. 2013;10(3):207–16.CrossRefPubMedGoogle Scholar
- 23.Engels EA et al. Cancer risk in people infected with human immunodeficiency virus in the United States. Int J Cancer. 2008;123(1):187–94.CrossRefPubMedGoogle Scholar
- 24.Bouvard V et al. A review of human carcinogens—part B: biological agents. Lancet Oncol. 2009;10(4):321–2.CrossRefPubMedGoogle Scholar
- 25.(UNAIDS), J.U.N.P.o.H.A., Global Report: UNAIDS report on the global AIDS epidemic 2013. 2013: Geneva, Switzerland.Google Scholar
- 26.•Mbulaiteye SM et al. Spectrum of cancers among HIV-infected persons in Africa: the Uganda AIDS-cancer registry match study. Int J Cancer. 2006;118(4):985–90. One of the few available linkage studies in sub-Saharan Africa: linked records of PLWH in Kyadondo County to the Kampala Cancer registry in Uganda.CrossRefPubMedGoogle Scholar
- 27.Akarolo-Anthony SN et al. Cancer burden among HIV-positive persons in Nigeria: preliminary findings from the Nigerian AIDS-cancer match study. Infect Agent Cancer. 2014;9(1):1.PubMedCentralCrossRefPubMedGoogle Scholar
- 28.Casper C. The increasing burden of HIV-associated malignancies in resource-limited regions. Annu Rev Med. 2011;62:157–70.CrossRefPubMedGoogle Scholar
- 29.Tanon A et al. The spectrum of cancers in West Africa: associations with human immunodeficiency virus. PLoS One. 2012;7(10), e48108.PubMedCentralCrossRefPubMedGoogle Scholar
- 30.Ferlay J, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. 2013; Available from: http://globocan.iarc.fr, accessed on July 12th 2015.
- 31.Dhir AA et al. Spectrum of HIV/AIDS related cancers in India. Cancer Causes Control. 2008;19(2):147–53.CrossRefPubMedGoogle Scholar
- 32.Pinzone MR et al. Epstein-barr virus- and Kaposi sarcoma-associated herpesvirus-related malignancies in the setting of human immunodeficiency virus infection. Semin Oncol. 2015;42(2):258–71.CrossRefPubMedGoogle Scholar
- 33.Nagaiah G et al. Ocular surface squamous neoplasia in patients with HIV infection in sub-Saharan Africa. Curr Opin Oncol. 2010;22(5):437–42.PubMedCentralCrossRefPubMedGoogle Scholar
- 34.Secretan B et al. A review of human carcinogens—part E: tobacco, areca nut, alcohol, coal smoke, and salted fish. Lancet Oncol. 2009;10(11):1033–4.CrossRefPubMedGoogle Scholar
- 35.Mdodo R et al. Cigarette smoking prevalence among adults with HIV compared with the general adult population in the United States: cross-sectional surveys. Ann Intern Med. 2015;162(5):335–44.CrossRefPubMedGoogle Scholar
- 36.•Helleberg M et al. Risk of cancer among HIV-infected individuals compared to the background population: impact of smoking and HIV. AIDS. 2014;28(10):1499–508. Danish study that calculates the impact of smoking on cancers in PLWH, including the population attributable fraction.CrossRefPubMedGoogle Scholar
- 37.Kirk GD et al. HIV infection is associated with an increased risk for lung cancer, independent of smoking. Clin Infect Dis. 2007;45(1):103–10.PubMedCentralCrossRefPubMedGoogle Scholar
- 38.Engels EA et al. Elevated incidence of lung cancer among HIV-infected individuals. J Clin Oncol. 2006;24(9):1383–8.CrossRefPubMedGoogle Scholar
- 39.Hessol NA et al. Lung cancer incidence and survival among HIV-infected and uninfected women and men. AIDS. 2015;29(10):1183–93.CrossRefPubMedGoogle Scholar
- 40.McGinnis KA et al. Hepatocellular carcinoma and non-Hodgkin’s lymphoma: the roles of HIV, hepatitis C infection, and alcohol abuse. J Clin Oncol. 2006;24(31):5005–9.CrossRefPubMedGoogle Scholar
- 41.De Martel, C, et al. Cancers attributable to infections among adults with HIV in the United States. AIDS, 2015.Google Scholar
- 42.Sulkowski MS. Viral hepatitis and HIV coinfection. J Hepatol. 2008;48(2):353–67.CrossRefPubMedGoogle Scholar
- 43.Brickman C, Palefsky JM. Human papillomavirus in the HIV-infected host: epidemiology and pathogenesis in the antiretroviral era. Curr HIV/AIDS Rep. 2015;12(1):6–15.CrossRefPubMedGoogle Scholar
- 44.Martin JN et al. Sexual transmission and the natural history of human herpesvirus 8 infection. N Engl J Med. 1998;338(14):948–54.CrossRefPubMedGoogle Scholar
- 45.••3rd Lo Re V et al. Hepatic decompensation in antiretroviral-treated patients co-infected with HIV and hepatitis C virus compared with hepatitis C virus-monoinfected patients: a cohort study. Ann Intern Med. 2014;160(6):369–79. Large cohort study using data from the Veterans Association Shows that patients with HIV/HCV have greater rates of hepatic decompensation than HCV monoinfection, despite use of antiretrovirals to effectively suppress HIV.PubMedGoogle Scholar
- 46.Balfour Jr HH et al. Age-specific prevalence of Epstein-Barr virus infection among individuals aged 6–19 years in the United States and factors affecting its acquisition. J Infect Dis. 2013;208(8):1286–93.CrossRefPubMedGoogle Scholar
- 47.Thompson LD et al. HIV-associated Hodgkin lymphoma: a clinicopathologic and immunophenotypic study of 45 cases. Am J Clin Pathol. 2004;121(5):727–38.CrossRefPubMedGoogle Scholar
- 48.Flavell KJ, Murray PG. Hodgkin’s disease and the Epstein-Barr virus. Mol Pathol. 2000;53(5):262–9.PubMedCentralCrossRefPubMedGoogle Scholar
- 49.Romani B, Engelbrecht S, Glashoff RH. Functions of Tat: the versatile protein of human immunodeficiency virus type 1. J Gen Virol. 2010;91(Pt 1):1–12.CrossRefPubMedGoogle Scholar
- 50.Kim RH et al. HIV-1 Tat enhances replicative potential of human oral keratinocytes harboring HPV-16 genome. Int J Oncol. 2008;33(4):777–82.PubMedGoogle Scholar
- 51.•Tugizov SM et al. HIV-associated disruption of mucosal epithelium facilitates paracellular penetration by human papillomavirus. Virology. 2013;446(1–2):378–88. In vitro study showing how HIV-derived tat and gp120 disrupt epithelial tight-cell junctions which allow HPV pseudovirion infection of the basal cell l epithelium.CrossRefPubMedGoogle Scholar
- 52.Dubrow R et al. HIV infection, aging, and immune function: implications for cancer risk and prevention. Curr Opin Oncol. 2012;24(5):506–16.PubMedCentralCrossRefPubMedGoogle Scholar
- 53.Guiguet M et al. Effect of immunodeficiency, HIV viral load, and antiretroviral therapy on the risk of individual malignancies (FHDH-ANRS CO4): a prospective cohort study. Lancet Oncol. 2009;10(12):1152–9.CrossRefPubMedGoogle Scholar
- 54.Bruyand M et al. Role of uncontrolled HIV RNA level and immunodeficiency in the occurrence of malignancy in HIV-infected patients during the combination antiretroviral therapy era: Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine Cohort. Clin Infect Dis. 2009;49(7):1109–16.PubMedCentralCrossRefPubMedGoogle Scholar
- 55.Pacheco YM et al. Increased risk of non-AIDS-related events in HIV subjects with persistent low CD4 counts despite cART in the CoRIS cohort. Antiviral Res. 2015;117:69–74.CrossRefPubMedGoogle Scholar
- 56.•Piketty C et al. Incidence of HIV-related anal cancer remains increased despite long-term combined antiretroviral treatment: results from the french hospital database on HIV. J Clin Oncol. 2012;30(35):4360–6. Data from French Hospital National Database on HIV on recent incidence rates of anal cancer in PLWH.CrossRefPubMedGoogle Scholar
- 57.Crum-Cianflone NF et al. Anal cancers among HIV-infected persons: HAART is not slowing rising incidence. AIDS. 2010;24(4):535–43.PubMedCentralCrossRefPubMedGoogle Scholar
- 58.Hunt PW. HIV and inflammation: mechanisms and consequences. Curr HIV/AIDS Rep. 2012;9(2):139–47.CrossRefPubMedGoogle Scholar
- 59.Lim SG et al. Loss of mucosal CD4 lymphocytes is an early feature of HIV infection. Clin Exp Immunol. 1993;92(3):448–54.PubMedCentralCrossRefPubMedGoogle Scholar
- 60.Marks MA et al. Markers of microbial translocation and risk of AIDS-related lymphoma. AIDS. 2013;27(3):469–74.CrossRefPubMedGoogle Scholar
- 61.•French MA et al. Serum immune activation markers are persistently increased in patients with HIV infection after 6 years of antiretroviral therapy despite suppression of viral replication and reconstitution of CD4+ T cells. J Infect Dis. 2009;200(8):1212–5. Shows that inflammation persists in PLWH despite effective ART.CrossRefPubMedGoogle Scholar
- 62.Neuhaus J et al. Markers of inflammation, coagulation, and renal function are elevated in adults with HIV infection. J Infect Dis. 2010;201(12):1788–95.PubMedCentralCrossRefPubMedGoogle Scholar
- 63.•Borges AH et al. Predicting risk of cancer during HIV infection: the role of inflammatory and coagulation biomarkers. AIDS. 2013;27(9):1433–41. Combines data from the control groups of 3 clinical trials in the U.S. to evaluate the risk of elevated inflammatory markers on the prospective risk of cancer Shows that activated inflammation and coagulation pathways are associated with increased cancer risk during HIV infection.PubMedCentralCrossRefPubMedGoogle Scholar
- 64.Vendrame E et al. Serum levels of cytokines and biomarkers for inflammation and immune activation, and HIV-associated non-Hodgkin B-cell lymphoma risk. Cancer Epidemiol Biomarkers Prev. 2014;23(2):343–9.PubMedCentralCrossRefPubMedGoogle Scholar
- 65.Shiels MS et al. Circulating inflammation markers and prospective risk for lung cancer. J Natl Cancer Inst. 2013;105(24):1871–80.PubMedCentralCrossRefPubMedGoogle Scholar
- 66.Kawabata S et al. Impact of HIV on lung tumorigenesis in an animal model. AIDS. 2015;29(5):633–5.PubMedGoogle Scholar
- 67.••Shiels MS, Pfeiffer RM, Engels EA. Age at cancer diagnosis among persons with AIDS in the United States. Ann Intern Med. 2010;153(7):452–60. One of the first papers to show that earlier age at cancer diagnosis in PLWH is largely due to differences in underlying age distribution compared to the general population, rather than an inherent effect of HIV itself.PubMedCentralCrossRefPubMedGoogle Scholar
- 68.Althoff KN et al. Comparison of risk and age at diagnosis of myocardial infarction, end-stage renal disease, and non-AIDS-defining cancer in HIV-infected versus uninfected adults. Clin Infect Dis. 2015;60(4):627–38.CrossRefPubMedGoogle Scholar
- 69.••Coghill AE et al. Elevated cancer-specific mortality among HIV-infected patients in the United States. J Clin Oncol. 2015;33(21):2376–83. HACM data that shows how cancer mortality in PLWH is elevated compared to the general population.CrossRefPubMedGoogle Scholar
- 70.Shiels MS et al. Cancer stage at diagnosis in patients infected with the human immunodeficiency virus and transplant recipients. Cancer. 2015;121(12):2063–71.CrossRefPubMedGoogle Scholar
- 71.••Marcus JL, et al. Survival Among HIV-Infected and HIV-Uninfected Individuals with Common Non-AIDS-Defining Cancers. Cancer Epidemiol Biomarkers Prev, 2015. Kaiser data that also shows increased cancer mortality in PLWH compared to non-HIV infected individualsGoogle Scholar
- 72.••Suneja G et al. Cancer treatment disparities in HIV-infected individuals in the United States. J Clin Oncol. 2014;32(22):2344–50. One of few available papers to evaluate treatment of cancer in PLWH Shows that PLWH are less likely to receive cancer treatment.PubMedCentralCrossRefPubMedGoogle Scholar
- 73.Suneja G et al. Disparities in the treatment and outcomes of lung cancer among HIV-infected individuals. AIDS. 2013;27(3):459–68.PubMedCentralCrossRefPubMedGoogle Scholar
- 74.Lohse N et al. Survival of persons with and without HIV infection in Denmark, 1995–2005. Ann Intern Med. 2007;146(2):87–95.CrossRefPubMedGoogle Scholar
- 75.Montoto S et al. HIV status does not influence outcome in patients with classical Hodgkin lymphoma treated with chemotherapy using doxorubicin, bleomycin, vinblastine, and dacarbazine in the highly active antiretroviral therapy era. J Clin Oncol. 2012;30(33):4111–6.CrossRefPubMedGoogle Scholar
- 76.White EC, et al. Comparison of Toxicity and Treatment Outcomes in HIV-positive Versus HIV-negative Patients With Squamous Cell Carcinoma of the Anal Canal. Am J Clin Oncol, 2014.Google Scholar
- 77.Moyer VA, U.S.P.S.T. Force. Screening for lung cancer: U.S. Preventive services task force recommendation statement. Ann Intern Med. 2014;160(5):330–8.CrossRefPubMedGoogle Scholar
- 78.Early Lung Cancer Diagnosis in HIV Infected Population With an Important Smoking History with Low Dose CT: a Pilot Study (EP48 HIV CHEST). July 17, 2015; Available from: https://clinicaltrials.gov/ct2/show/NCT01207986.
- 79.National Lung Screening Trial Research, T. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365(5):395–409.CrossRefGoogle Scholar
- 80.Topical or Ablative Treatment in Preventing Anal Cancer in Patients With HIV and Anal High-Grade Squamous Intraepithelial Lesions. March 11, 2015; Available from: https://www.clinicaltrials.gov/ct2/show/NCT02135419.
- 81.Park IU, Palefsky JM. Evaluation and management of anal intraepithelial neoplasia in HIV-negative and HIV-positive men who have sex with men. Curr Infect Dis Rep. 2010;12(2):126–33.PubMedCentralCrossRefPubMedGoogle Scholar
- 82.Adefuye PO et al. Trials and projects on cervical cancer and human papillomavirus prevention in sub-Saharan Africa. Vaccine. 2013;31 Suppl 5:F53–9.CrossRefPubMedGoogle Scholar
- 83.Adebamowo CA et al. Challenges in the detection, prevention, and treatment of HIV-associated malignancies in low- and middle-income countries in Africa. J Acquir Immune Defic Syndr. 2014;67 Suppl 1:S17–26.PubMedCentralCrossRefPubMedGoogle Scholar