Are Non-HIV Malignancies Increased in the HIV-Infected Population?

  • Aaron P. Thrift
  • Elizabeth Y. ChiaoEmail author
Tropical, Travel and Emerging Infections (L Chen and A Boggild, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Tropical, Travel and Emerging Infections


Purpose of review

The introduction of antiretroviral therapy (ART) has revolutionized HIV infection management, resulting in improved outcomes and survival for people living with HIV (PLWH). However, as PLWH are living longer and aging, non-AIDS-defining cancers (NADCs) represent a significant source of morbidity and mortality in the HIV-infected population. Here, we review the epidemiology of NADCs in PLWH.

Recent findings

Cancer mortality among PLWH is much higher than that among the general population. Up to 10% of deaths among PLWH have been attributed to NADCs. Furthermore, PLWH have an increased risk for specific NADCs, including lung cancer, hepatocellular carcinoma, head and neck cancers, anal cancer, and Hodgkin lymphoma. In the past decade, the incidence rates of AIDS-defining cancers (ADCs) have been decreasing while the incidence rates of NADCs have been increasing. In particular, the incidence of specific NADCs are changing at different rates. For example through 2010, the incidence rates for anal, liver, and prostate cancers among PLWH had increased, while incidence rates for lung cancer had decreased and incidence rates for colorectal cancer remained relatively stable over time. However, as early ART becomes more prevalent and the percentage of PLWH over 50 increases, these trends may evolve further.


Incidence of NADCs should be expected to increase further as the PLWH population continues to age. Screening and prevention for these cancers among the HIV-infected population should be emphasized.


HIV/AIDS Cancer Epidemiology Antiretroviral therapy ART 



NIH R01 CA206479 (Chiao), NIH P30 AI027767 (Thrift)

Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflict of interest.

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.


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  1. 1.
    Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998;338(13):853–60.CrossRefPubMedGoogle Scholar
  2. 2.
    CDC. HIV in the United States: At A Glance. 2017.
  3. 3.
    Shiels MS, Pfeiffer RM, Gail MH, Hall HI, Li J, Chaturvedi AK, et al. Cancer burden in the HIV-infected population in the United States. J Natl Cancer Inst. 2011;103(9):753–62.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Robbins HA, Shiels MS, Pfeiffer RM, Engels EA. Epidemiologic contributions to recent cancer trends among HIV-infected people in the United States. AIDS (London, England). 2014;28(6):881–90.CrossRefGoogle Scholar
  5. 5.
    Morlat P, Roussillon C, Henard S, Salmon D, Bonnet F, Cacoub P, et al. Causes of death among HIV-infected patients in France in 2010 (national survey): trends since 2000. AIDS (London, England). 2014;28(8):1181–91.CrossRefGoogle Scholar
  6. 6.
    Goehringer F, Bonnet F, Salmon D, Cacoub P, Paye A, Chêne G, et al. Causes of death in HIV-infected individuals with immunovirologic success in a national prospective survey. AIDS Res Hum Retrovir. 2017;33(2):187–93.CrossRefPubMedGoogle Scholar
  7. 7.
    Simard EP, Pfeiffer RM, Engels EA. Mortality due to cancer among people with AIDS: a novel approach using registry-linkage data and population attributable risk methods. AIDS (London, England). 2012;26(10):1311–8.CrossRefGoogle Scholar
  8. 8.
    Simard EP, Engels EA. Cancer as a cause of death among people with AIDS in the United States. Clin Infect Dis. 2010;51(8):957–62.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Shiels MS, Cole SR, Kirk GD, Poole C. A meta-analysis of the incidence of non-AIDS cancers in HIV-infected individuals. J Acquir Immune Defic Syndr. 2009;52(5):611–22.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Koethe JR, Jenkins CA, Lau B, Shepherd BE, Justice AC, Tate JP, et al. North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). Rising obesity prevalence and weight gain among adults starting antiretroviral therapy in the United States and Canada. AIDS Res Hum Retrovir. 2016;32(1):50–8.Google Scholar
  11. 11.
    Galvan FH, Bing EG, Fleishman JA, London AS, Caetano R, Burnam MA, et al. The prevalence of alcohol consumption and heavy drinking among people with HIV in the United States: results from the HIV Cost and Services Utilization Study. J Stud Alcohol. 2002;63(2):179–86.CrossRefPubMedGoogle Scholar
  12. 12.
    Rohner E, Wyss N, Heg Z, Faralli Z, Mbulaiteye SM, Novak U, et al. HIV and human herpesvirus 8 co-infection across the globe: systematic review and meta-analysis. Int J Cancer. 2016;138(1):45–54.CrossRefPubMedGoogle Scholar
  13. 13.
    Koziel MJ, Peters MG. Viral hepatitis in HIV infection. N Engl J Med. 2007;356(14):1445–54.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Rowhani-Rahbar A, Hawes SE, Sow PS, Toure P, Feng Q, Dem A, et al. The impact of HIV status and type on the clearance of human papillomavirus infection among Senegalese women. J Infect Dis. 2007;196(6):887–94.CrossRefPubMedGoogle Scholar
  15. 15.
    Ucciferri C, Tamburro M, Falasca K, Sammarco ML, Ripabelli G, Vecchiet J. Prevalence of anal, oral, penile and urethral human papillomavirus in HIV infected and HIV uninfected men who have sex with men. J Med Virol. 2018;90(2):358–66.CrossRefPubMedGoogle Scholar
  16. 16.
    Mdodo R, Frazier EL, Dube SR, Mattson CL, Sutton MY, Brooks JT, 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
  17. 17.
    •• Engels EA, Yanik EL, Wheeler W, et al. Cancer-attributable mortality among people with treated human immunodeficiency virus infection in North America. Clin Infect Dis. 2017;65(4):636–43. This prospective cohort study among 46,956 individuals in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) showed that approximately 10% of deaths in people living with HIV receiving ART were due to cancer. The fraction of deaths due to cancer increased over time and is expected to further increase as AIDS-related mortality decreases and the HIV-infected population ages. CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    •• Hernandez-Ramirez RU, Shiels MS, Dubrow R, Engels EA. Cancer risk in HIV-infected people in the USA from 1996 to 2012: a population-based, registry-linkage study. Lancet HIV. 2017;4(11):e495–504. This article decribes the risk of cancer among the HIV/AIDS Cancer Match Study, the largest population-based study of cancer among HIV-infected individuals. They showed that risk for some non-AIDS-defining cancers (i.e., anus, liver, and lung) remain high among people with HIV during the modern treatment era. CrossRefPubMedGoogle Scholar
  19. 19.
    Mbulaiteye SM, Bhatia K, Adebamowo C, Sasco AJ. HIV and cancer in Africa: mutual collaboration between HIV and cancer programs may provide timely research and public health data. Infect Agent Cancer. 2011;6(1):16.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Tanaka LF, Latorre M, Gutierrez EB, Heumann C, Herbinger KH, Froeschl G. Trends in the incidence of AIDS-defining and non-AIDS-defining cancers in people living with AIDS: a population-based study from Sao Paulo, Brazil. Int J STD AIDS. 2017;28(12):1190–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Yanik EL, Katki HA, Engels EA. Cancer risk among the HIV-infected elderly in the United States. AIDS. 2016;30(10):1663–8.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    •• 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(4):468–75. This study showed that there is no acceleration of cancer development among people living with HIV; for most cancers, the mean age at diagnoses is not different between individuals with and without HIV infection. PubMedPubMedCentralGoogle Scholar
  24. 24.
    Hleyhel M, Hleyhel M, Bouvier AM, 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 (London, England). 2014;28(14):2109–18.CrossRefGoogle Scholar
  25. 25.
    Weinberger AH, Smith PH, Funk AP, Rabin S, Shuter J. Sex differences in tobacco use among persons living with HIV/AIDS: a systematic review and meta-analysis. J Acquir Immune Defic Syndr. 2017;74(4):439–53.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Sigel K, Wisnivesky J, Gordon K, Dubrow R, Justice A, Brown ST, et al. HIV as an independent risk factor for incident lung cancer. AIDS (London, England). 2012;26(8):1017–25.CrossRefGoogle Scholar
  27. 27.
    Engels EA, Brock MV, Chen J, Hooker CM, Gillison M, Moore RD. Elevated incidence of lung cancer among HIV-infected individuals. J Clin Oncol. 2006;24(9):1383–8.CrossRefPubMedGoogle Scholar
  28. 28.
    Levine AM, Seaberg EC, Hessol NA, Preston-Martin S, Silver S, Cohen MH, et al. HIV as a risk factor for lung cancer in women: data from the Women’s Interagency HIV Study. J Clin Oncol. 2010;28(9):1514–9.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Hessol NA, Martinez-Maza O, Levine AM, et al. Lung cancer incidence and survival among HIV-infected and uninfected women and men. AIDS (London, England). 2015;29(10):1183–93.CrossRefGoogle Scholar
  30. 30.
    Sigel K, Wisnivesky J, Crothers K, et al. Immunological and infectious risk factors for lung cancer in US veterans with HIV: a longitudinal cohort study. Lancet HIV. 2017;4(2):e67–73.CrossRefPubMedGoogle Scholar
  31. 31.
    Marcus JL, Leyden WA, Chao CR, Horberg MA, Klein DB, Quesenberry CP Jr, et al. Immunodeficiency, AIDS-related pneumonia, and risk of lung cancer among HIV-infected individuals. AIDS (London, England). 2017;31(7):989–93.CrossRefGoogle Scholar
  32. 32.
    Silverberg MJ, Chao C, Leyden WA, Xu L, Horberg MA, Klein D, et al. HIV infection, immunodeficiency, viral replication, and the risk of cancer. Cancer Epidemiol Biomark Prev. 2011;20(12):2551–9.CrossRefGoogle Scholar
  33. 33.
    Prosperi MC, Cozzi-Lepri A, Castagna A, Mussini C, Murri R, Giacometti A, et al. Incidence of malignancies in HIV-infected patients and prognostic role of current CD4 cell count: evidence from a large Italian cohort study. Clin Infect Dis. 2010;50(9):1316–21.CrossRefPubMedGoogle Scholar
  34. 34.
    • Reddy KP, Kong CY, Hyle EP, et al. Lung cancer mortality associated with smoking and smoking cessation among people living with HIV in the United States. JAMA Intern Med. 2017;177(11):1613–21. This simulation study showed that there is a large burden of lung cancer among people living with HIV in the USA such that lung cancer is now a leading cause of death. For people living with HIV who adhere to ART, smoking rather than HIV itself contributes more to poor health and mortality risk. CrossRefPubMedGoogle Scholar
  35. 35.
    • Coghill AE, Pfeiffer RM, Shiels MS, Engels EA. Excess mortality among HIV-infected individuals with cancer in the United States. Cancer Epidemiol Biomark Prev. 2017;26(7):1027–33. This large cohort study using data from the HIV/AIDS Cancer Match Study and the National Center for Health Statistics showed that individuals with both HIV and cancer are at especially high risk for mortality compared to individuals with either HIV or cancer. CrossRefGoogle Scholar
  36. 36.
    Patel P, Hanson DL, Sullivan PS, Novak RM, Moorman AC, Tong TC, 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
  37. 37.
    Silverberg MJ, Chao C, Leyden WA, Xu L, Tang B, Horberg MA, et al. HIV infection and the risk of cancers with and without a known infectious cause. AIDS (London, England). 2009;23(17):2337–45.CrossRefGoogle Scholar
  38. 38.
    Marcus JL, Chao CR, Leyden WA, Xu L, Klein DB, Horberg MA, et al. Prostate cancer incidence and prostate-specific antigen testing among HIV-positive and HIV-negative men. J Acquir Immune Defic Syndr. 2014;66(5):495–502.CrossRefPubMedGoogle Scholar
  39. 39.
    Shiels MS, Goedert JJ, Moore RD, Platz EA, Engels EA. Reduced risk of prostate cancer in U.S. men with AIDS. Cancer Epidemiol Biomark Prev. 2010;19(11):2910–5.CrossRefGoogle Scholar
  40. 40.
    Bedimo RJ, McGinnis KA, Dunlap M, Rodriguez-Barradas MC, Justice AC. Incidence of non-AIDS-defining malignancies in HIV-infected versus noninfected patients in the HAART era: impact of immunosuppression. J Acquir Immune Defic Syndr. 2009;52(2):203–8.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Hessol NA, Pipkin S, Schwarcz S, Cress RD, Bacchetti P, Scheer S. The impact of highly active antiretroviral therapy on non-AIDS-defining cancers among adults with AIDS. Am J Epidemiol. 2007;165(10):1143–53.CrossRefPubMedGoogle Scholar
  42. 42.
    White DL, Thrift AP, Kanwal F, Davila J, El-Serag HB. Incidence of hepatocellular carcinoma in all 50 United States, from 2000 through 2012. Gastroenterology. 2017;152(4):812–820.e815.CrossRefPubMedGoogle Scholar
  43. 43.
    Thrift AP, El-Serag HB, Kanwal F. Global epidemiology and burden of HCV infection and HCV-related disease. Nat Rev Gastroenterol Hepatol. 2017;14(2):122–32.CrossRefPubMedGoogle Scholar
  44. 44.
    Clifford GM, Rickenbach M, Polesel J, Dal Maso L, Steffen I, Ledergerber B, et al. Influence of HIV-related immunodeficiency on the risk of hepatocellular carcinoma. AIDS (London, England). 2008;22(16):2135–41.CrossRefGoogle Scholar
  45. 45.
    McGinnis KA, Fultz SL, Skanderson M, Conigliaro J, Bryant K, Justice AC. 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
  46. 46.
    Di Benedetto N, Peralta M, Alvarez E, et al. Incidence of hepatocellular carcinoma in hepatitis C cirrhotic patients with and without HIV infection: a cohort study, 1999-2011. Ann Hepatol. 2013;13(1):38–44.PubMedGoogle Scholar
  47. 47.
    Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020–2.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56(4):908–43.Google Scholar
  49. 49.
    Verslype C, Rosmorduc O, Rougier P. Hepatocellular carcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl 7):vii41–8.CrossRefPubMedGoogle Scholar
  50. 50.
    Wilkins E, Nelson M, Agarwal K, et al. British HIV Association guidelines for the management of hepatitis viruses in adults infected with HIV 2013. HIV Med. 2013;14(Suppl 4):1–71.PubMedGoogle Scholar
  51. 51.
    Gillison ML, Chaturvedi AK, Anderson WF, Fakhry C. Epidemiology of human papillomavirus-positive head and neck squamous cell carcinoma. J Clin Oncol. 2015;33(29):3235–42.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    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(18):1500–10.CrossRefPubMedGoogle Scholar
  53. 53.
    Chaturvedi AK, Madeleine MM, Biggar RJ, Engels EA. Risk of human papillomavirus-associated cancers among persons with AIDS. J Natl Cancer Inst. 2009;101(16):1120–30.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Chew EY, Hartman CM, Richardson PA, Zevallos JP, Sikora AG, Kramer JR, et al. Risk factors for oropharynx cancer in a cohort of HIV-infected veterans. Oral Oncol. 2017;68:60–6.CrossRefPubMedGoogle Scholar
  55. 55.
    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(9581):59–67.CrossRefPubMedGoogle Scholar
  56. 56.
    Silverberg MJ, Lau B, Justice AC, Engels E, Gill MJ, Goedert JJ, et al. Risk of anal cancer in HIV-infected and HIV-uninfected individuals in North America. Clin Infect Dis. 2012;54(7):1026–34.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Kowalkowski MA, Day RS, Du XL CW, Chiao EY. Cumulative HIV viremia and non-AIDS-defining malignancies among a sample of HIV-infected male veterans. J Acquir Immune Defic Syndr. 2014;67(2):204–11.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Duncan KC, Chan KJ, Chiu CG, Montaner JSG, Coldman AJ, Cescon A, et al. HAART slows progression to anal cancer in HIV-infected MSM. AIDS (London, England). 2015;29(3):305–11.CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of MedicineBaylor College of MedicineHoustonUSA
  2. 2.Dan L Duncan Comprehensive Cancer CenterBaylor College of MedicineHoustonUSA
  3. 3.Center for Innovations in Quality, Effectiveness and Safety (IQuESt)Michael E. DeBakey VA Medical Center, HSR&D Center of Innovation (152)HoustonUSA

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