Prognostication of Malignancies in HIV Infection

  • Steven Oppenheim MD
  • Faiza Yasin MD MHS
  • Ronald Chow BMSc
  • Brinda Emu MD
  • Trinh Bui PharmD
  • Elizabeth Horn Prsic MD

Download PDF

Background: Life-expectancy among persons living with HIV/AIDS (PLWH) has increased substantially in the era of combined antiretroviral therapy (cART) resulting in increased HIV viral suppression (1) and decreased progression to advanced HIV/AIDS. As PLWH are living longer, cancer epidemiology among this group has evolved, both due to incidental cancers found more commonly in older age, but also due to the propensity for certain malignancies to develop at higher rates in PLWH. Cancer burden among PLWH is likely a product of several factors including persistent immune dysfunction and chronic inflammation despite cART (2), higher rates of risk factors for cancer (3), and higher rates of co-infection with oncogenic viruses (4). PLWH are also reported to be diagnosed with more aggressive and advanced disease stages of cancer (5). Hence, higher cancer-specific mortality compared to individuals without HIV has been noted (5,6). Fast Fact #213 discussed the prognostic principles in adults with HIV or AIDS for many life-threatening complications of HIV infection. This Fast Fact presents survival data for malignancies commonly arising in the setting of HIV/AIDs. 

Classification of malignancies in PLWH: Malignancies in PLWH are classified as non-AIDS defining malignancies (NADMs) (7,8) and AIDS-defining malignancies (ADMs). HIV treatment with cART has decreased rates of ADM’s, in part due to improved immune function and higher CD4 T-cell count and shifted the burden of malignancy to NADMs. 

Prognosis in AIDS-Defining Malignancies (ADM)(9):  The overall burden of ADMs is expected to continue to decrease over time, mostly due to decreases in Kaposi’s Sarcoma (KS) and Non-Hodgkins Lymphoma (NHL) with cART treatment (10).

  • HIV-related/epidemic KS: KS is a grossly violaceous spindle cell tumor, associated with human herpesvirus-8 infection. Risk of HIV-associated KS increases with lower CD4 T-cell count, but remains higher in PLWH compared to the general population (11). Treatment with cART is the mainstay of therapy for limited disease and often results in response within several months (12). Systemic anthracycline based chemotherapy is used for treatment of advanced KS or visceral KS. Immune checkpoint blockers like pembrolizumab may be safe and effective in HIV-associated KS, (13-15). The 5-year survival has been estimated to be 92% for mucocutaneous KS and 82.6% for visceral KS (16). 
  • Invasive cervical cancer: Incidence has not declined in the cART era, though PLWH on cART who are virally suppressed with stable high CD4 count have a lower risk of high-risk human papillomavirus virus (HPV) persistence and high-grade cervical dysplasia (17). Higher mortality, and recurrence rate persists among PLWH compared to those not living with HIV (18,19). Additionally, PLWH who have a cervix may have a 6-fold higher risk of developing cervical cancer compared to those without HIV (20). Cervical cancer has a median survival of 5.1 years and a 10- year survival of 78.5% (21).
  • ADM NHL: These include Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), primary CNS lymphoma (PCNSL), peripheral T-cell lymphoma (PTCL), and follicular lymphoma. In general, 5-year survival rates of all NHL subtypes in HIV infected persons are lower (22) than the general population, in part because PLWH are more likely to be diagnosed at advanced stages of DLBCL (22-24). While the 5-year overall survival rates from a large US cancer registry are estimated to be 41.1% for DLBCL, 47.6% for Burkitt lymphoma, 32.3% for PTCL, and 68% for follicular lymphoma (22), recent evidence has led to following updates regarding 5-year survival rates for specific ADM NHLs:
    • Dose-adjusted treatment for BL may have an improved 5-year overall survival of 87.0% (25-27).
    • Retrospective studies show 5-year survival rates of 48-60% for PCNSL in the cART era (25-27). 
    • Survival rates among PLWH with NHLs are substantially lower in Sub-Saharan Africa, a region which accounts for the majority of PLWH in the world. These lower survival rates are likely due to late diagnoses and limitations in healthcare infrastructure (28,29).

Prognosis in Non-AIDS-Defining Malignancies Cancers (NADM): NADMs are now the leading cause of mortality in PLWH in the developed world and account for most HIV-associated malignancies (8). The most common NADMs with elevated rates among PLWH in the US are lung cancer, anal cancer, liver cancer, oral cavity/ pharyngeal cancers, and Hodgkin’s lymphoma. 

  • Non-small cell lung cancer (NSCLC): Median survival for PLWH is estimated to be 6-12.4 months compared to 20-22.8 months in patients with NSCLC who are not living with HIV (30-33).
  • Anal cancer: Median disease-free survival was 79.7 months in PLWH compared to 127.9 in persons who are not living with HIV (34,35). 
  • Hepatocellular cancer (HCC): There is marked heterogeneity in survival among PLWH with due to factors such as hepatitis C virus (HCV) and/or hepatitis B virus coinfection, treatment for HCV, cART treatment, and severity of liver disease. One global multi-cohort study suggested a survival range of 3 to 16 months depending on stage at diagnosis and a medial survival of 4 months (36).
  • Hodgkin’s Lymphoma: PLWH with Hodgkin’s disease experience complete remission rates of 74-89% and overall survival rates at 5-years ranging 76-81% when treated with curative-intent treatment combined with cART (37). While PLWH presented with more aggressive features at diagnosis, there were no differences in response rate to treatment, or disease-free survival (37,38). 
  • Head and neck squamous cell carcinoma: Overall 3-year survival is estimated to be 60% (39). There is conflicting data on whether PLWH and head and neck cancer have worsened survival than the general population (40). 


1.         HIV.gov. The Global HIV/AIDS Epidemic 2020. Available from: https://www.hiv.gov/hiv-basics/overview/data-and-trends/global-statistics.

2.         Wada NI, Jacobson LP, Margolick JB, Breen EC, Macatangay B, Penugonda S, et al. The effect of HAART-induced HIV suppression on circulating markers of inflammation and immune activation. Aids. 2015;29(4):463-71.

3.         Helleberg M, Gerstoft J, Afzal S, Kronborg G, Larsen CS, Pedersen C, 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.

4.         Park LS, Tate JP, Sigel K, Brown ST, Crothers K, Gibert C, et al. Association of Viral Suppression With Lower AIDS-Defining and Non-AIDS-Defining Cancer Incidence in HIV-Infected Veterans: A Prospective Cohort Study. Ann Intern Med. 2018;169(2):87-96.

5.         Coghill AE, Han X, Suneja G, Lin CC, Jemal A, Shiels MS. Advanced stage at diagnosis and elevated mortality among US patients with cancer infected with HIV in the National Cancer Data Base. Cancer. 2019;125(16):2868-76.

6.         Coghill AE, Shiels MS, Suneja G, Engels EA. Elevated Cancer-Specific Mortality Among HIV-Infected Patients in the United States. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2015;33(21):2376-83.

7.         Engels EA, Yanik EL, Wheeler W, Gill MJ, Shiels MS, Dubrow R, et al. Cancer-Attributable Mortality Among People With Treated Human Immunodeficiency Virus Infection in North America. Clinical Infectious Diseases. 2017;65(4):636-43.

8.         Rubinstein PG, Aboulafia DM, Zloza A. Malignancies in HIV/AIDS: from epidemiology to therapeutic challenges. Aids. 2014;28(4):453-65.

9.         Izadmehr S, Leapman M, Hobbs AR, Katsigeorgis M, Nabizada-Pace F, Jazayeri SB, et al. Clinical characteristics and outcomes of HIV-seropositive men treated with surgery for prostate cancer. International Urology and Nephrology. 2016;48(10):1639-45.

10.       Shiels MS, Islam JY, Rosenberg PS, Hall HI, Jacobson E, Engels EA. Projected Cancer Incidence Rates and Burden of Incident Cancer Cases in HIV-Infected Adults in the United States Through 2030. Ann Intern Med. 2018;168(12):866-73.

11.       Yarchoan R, Uldrick TS. HIV-Associated Cancers and Related Diseases. The New England journal of medicine. 2018;378(11):1029-41.

12.       Cesarman E, Damania B, Krown SE, Martin J, Bower M, Whitby D. Kaposi sarcoma. Nature Reviews Disease Primers. 2019;5 (1) (no pagination)(9).

13.       Uldrick TS, Gonçalves PH, Abdul-Hay M, Claeys AJ, Emu B, Ernstoff MS, et al. Assessment of the Safety of Pembrolizumab in Patients With HIV and Advanced Cancer—A Phase 1 Study. JAMA Oncology. 2019;5(9):1332-9.

14.       Cook MR, Kim C. Safety and Efficacy of Immune Checkpoint Inhibitor Therapy in Patients With HIV Infection and Advanced-Stage Cancer: A Systematic Review. JAMA Oncology. 2019;5(7):1049-54.

15.       Galanina N, Goodman AM, Cohen PR, Frampton GM, Kurzrock R. Successful Treatment of HIV-Associated Kaposi Sarcoma with Immune Checkpoint Blockade. Cancer immunology research. 2018;6(10):1129-35.

16.       Hleyhel M, Belot A, Bouvier A-M, Tattevin P, Pacanowski J, Genet P, et al. Trends in survival after cancer diagnosis among HIV-infected individuals between 1992 and 2009. Results from the FHDH-ANRS CO4 cohort. International Journal of Cancer. 2015;137(10):2443-53.

17.       Kelly H, Weiss HA, Benavente Y, de Sanjose S, Mayaud P. Association of antiretroviral therapy with high-risk human papillomavirus, cervical intraepithelial neoplasia, and invasive cervical cancer in women living with HIV: a systematic review and meta-analysis. The lancet HIV. 2018;5(1):e45-e58.

18.       Dryden-Peterson S, Bvochora-Nsingo M, Suneja G, Efstathiou JA, Grover S, Chiyapo S, et al. HIV Infection and Survival Among Women With Cervical Cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2016;34(31):3749-57.

19.       Teixeira da Costa Lodi C, Michelin MA, Miranda Lima MI, Murta EFC, Braga LDC, Montes L, et al. Predicting cervical intraepithelial neoplasia recurrence in HIV-infected and -noninfected women by detecting aberrant promoter methylation in the CDH1, TIMP3, and MGMT genes. Arch Gynecol Obstet. 2018;298(5):971-9.

20.       Stelzle D, Tanaka LF, Lee KK, Ibrahim Khalil A, Baussano I, Shah ASV, et al. Estimates of the global burden of cervical cancer associated with HIV. The Lancet Global health. 2021;9(2):e161-e9.

21.       Achenbach CJ, Cole SR, Kitahata MM, Casper C, Willig JH, Mugavero MJ, et al. Mortality after cancer diagnosis in HIV-infected individuals treated with antiretroviral therapy. AIDS (London, England). 2011;25(5):691-700.

22.       Han X, Jemal A, Hulland E, Simard EP, Nastoupil L, Ward E, et al. HIV Infection and Survival of Lymphoma Patients in the Era of Highly Active Antiretroviral Therapy. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2017;26(3):303-11.

23.       Chao C, Xu L, Abrams D, Leyden W, Horberg M, Towner W, et al. Survival of non-Hodgkin lymphoma patients with and without HIV infection in the era of combined antiretroviral therapy. Aids. 2010;24(11):1765-70.

24.       Gopal S, Martin KE, Richards KL, Eron JJ. Clinical presentation, treatment, and outcomes among 65 patients with HIV-associated lymphoma treated at the University of North Carolina, 2000-2010. AIDS research and human retroviruses. 2012;28(8):798-805.

25.       Gupta NK, Nolan A, Omuro A, Reid EG, Wang CC, Mannis G, et al. Long-term survival in AIDS-related primary central nervous system lymphoma. Neuro Oncol. 2017;19(1):99-108.

26.       Moulignier A, Lamirel C, Picard H, Lebrette MG, Amiel C, Hamidi M, et al. Long-term AIDS-related PCNSL outcomes with HD-MTX and combined antiretroviral therapy. Neurology. 2017;89(8):796-804.

27.       Noy A. Optimizing treatment of HIV-associated lymphoma. Blood. 2019;134(17):1385-94.

28.       Chinula L, Moses A, Gopal S. HIV-associated malignancies in sub-Saharan Africa: progress, challenges, and opportunities. Curr Opin HIV AIDS. 2017;12(1):89-95.

29.       Gopal S, Gross TG. How I treat Burkitt lymphoma in children, adolescents, and young adults in sub-Saharan Africa. Blood. 2018;132(3):254-63.

30.       Hysell K, Yusuf R, Barakat L, Virata M, Gan G, Deng Y, et al. Decreased Overall Survival in HIV-associated Non-small-cell Lung Cancer. Clinical lung cancer. 2020.

31.       Sigel K, Crothers K, Dubrow R, Krauskopf K, Jao J, Sigel C, et al. Prognosis in HIV-infected patients with non-small cell lung cancer. British Journal of Cancer. 2013;109(7):1974-80.

32.       Sigel K, Makinson A, Thaler J. Lung cancer in persons with HIV. Current Opinion in HIV and AIDS. 2017;12(1):31-8.

33.       Hessol NA, Martínez-Maza O, Levine AM, Morris A, Margolick JB, Cohen MH, et al. Lung cancer incidence and survival among HIV-infected and uninfected women and men. AIDS. 2015;29(10).

34.       Susko M, Wang CJ, Lazar AA, Kim S, Laffan A, Feng M, et al. Factors Impacting Differential Outcomes in the Definitive Radiation Treatment of Anal Cancer Between HIV-Positive and HIV-Negative Patients. Oncologist. 2020;25(9):772-9.

35.       Camandaroba MPG, Iseas S, Oliveira C, Taboada RG, Xerfan MP, Mauro CC, et al. Disease-Free Survival and Time to Complete Response After Definitive Chemoradiotherapy for Squamous-Cell Carcinoma of the Anus According to HIV Infection. Clin Colorectal Cancer. 2020;19(3):e129-e36.

36.       Pinato DJ, Allara E, Chen TY, Trevisani F, Minguez B, Zoli M, et al. Influence of HIV Infection on the Natural History of Hepatocellular Carcinoma: Results From a Global Multicohort Study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2019;37(4):296-304.

37.       Hentrich M, Spina M. The management of hiv-hodgkin lymphoma. Hematologic Malignancies. 2020:335-47.

38.       Sorigué M, García O, Tapia G, Baptista MJ, Moreno M, Mate JL, et al. HIV-infection has no prognostic impact on advanced-stage Hodgkin lymphoma. Aids. 2017;31(10):1445-9.

39.       Nayyar SS, Thiagarajan S, Malik A, D’Cruz A, Chaukar D, Patil P, et al. Head and neck squamous cell carcinoma in HIV, HBV and HCV seropositive patients – Prognosis and its predictors. Journal of cancer research and therapeutics. 2020;16(3):619-23.

40.       Katiyar VA, T.; Gupta, S.; Rubinstein, P.; Rosen, F.R. HIV assoicated head and neck cancers in an inner-city minority population. Journal of Clinical Oncology. 2019;37(15):suppl.e13124.

Author Affiliation: One Medical, San Francisco, CA (FY), Yale New Haven Hospital, New Haven, CT (RC, BE, TB, EHP)

Version History:  Originally published March 2009.  Significant revision occurred in February 2016 by Steven Oppenheim MD. Another significant revision occurred in March 2021 by Faiza Yasin MD MHS, Ronald Chow BMSc, Brinda Emu MD, Trinh Bui Pharm D, and Elizabeth Horn Prsic MD to reflect updates in the literature.

Conflict of Interest: None