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HIV Positive People Are at Higher Risk for Cancer, especially Malignancies Linked to Infectious Pathogens or Smoking

People with HIV have an increased risk of developing non-AIDS-defining cancers, especially malignancies with infectious causes (such as anal and liver cancer) and those associated with tobacco smoking, according to a meta-analysis of 18 studies published in the September 17, 2009 advance online issue of the Journal of Acquired Immune Deficiency Syndromes.

A growing body of evidence indicates that people with HIV are at higher risk for several non-AIDS-defining cancers in the highly active antiretroviral therapy (HAART) era, even at CD4 cell levels well above the 200 cells/mm³ "danger zone."

Traditionally, only Kaposi's sarcoma, non-Hodgkin lymphoma (NHL), and cervical cancer have been classified as AIDS-defining malignancies. However, anal cancer is caused by the same strains of human papillomavirus (HPV) as cervical cancer, and several other malignancies have a known or suspected link to infectious pathogens.

In the present study, Meredith Shiels from Johns Hopkins Bloomberg School of Public Health and colleagues performed a meta-analysis using standardized incidence ratios (SIRs) -- a measure comparing incidence rates among HIV positive individuals and the general population -- from 18 studies of non-AIDS cancers in HIV positive people conducted between 1981 and 2007.

Using this information, they estimated summary SIRs for 34 non-AIDS malignancies among HIV positive individuals compared with general population rates, both overall and stratified by sex, AIDS diagnosis, and time of diagnosis (pre-HAART vs HAART eras).

Results

• 4797 cases of non-AIDS cancers occurred among the total 625,716 HIV positive individuals in the selected studies.
• Lung cancer (847 cases), Hodgkin lymphoma (643 cases), and anal cancer (254 cases) were the most commonly diagnosed malignancies.
• SIRs were elevated for several cancers, indicating higher incidence among people with HIV.
• Overall, HIV positive people were twice as likely to develop non-AIDS malignancies compared with the general population (SIR = 2).
• In particular, HIV positive people were more likely to develop cancers associated with infectious pathogens:
  • Anal cancer (due to HPV): SIR = 28;
  • Hodgkin lymphoma (associated with Epstein-Barr virus): SIR = 11;
  • Liver cancer (typically linked to hepatitis B or C): SIR = 5.6.
• People with HIV also had higher rates of cancers associated with tobacco smoking:
  • Lung cancer: SIR = 2.6;
  • Kidney cancer: SIR = 1.7;
  • Laryngeal cancer: SIR = 1.5.
• However, HIV positive people did not have higher rates of breast cancer or prostate cancer.
• Overall, HIV positive men had a higher risk of non-AIDS-defining cancers than HIV positive women.
• Having an AIDS diagnosis was associated with higher SIRs for Hodgkin lymphoma, leukemia, lung, and brain cancer, and for all non-AIDS cancers combined (SIR = 3.17).
• Incidence of all non-AIDS malignancies combined decreased slightly after the advent of HAART.

Based on these findings, the investigators concluded, "HIV-infected individuals may be at an increased risk of developing non-AIDS cancers, particularly those associated with infections and smoking."

"An association with advanced immune suppression was suggested for certain cancers," they added.

In their discussion, however, they noted that, "it remains unclear whether HIV-infected individuals are truly at a greater risk of non-AIDS-defining cancers, or if confounding by unadjusted cancer risk factors may be responsible for the apparent elevated increase."

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC.

10/09/09

Reference

MS Shiels, SR Cole SR, GD Kirk, and others. A Meta-Analysis of the Incidence of Non-AIDS Cancers in HIV-Infected Individuals. Journal of Acquired Immune Deficiency Syndromes. September 17, 2009 (epub ahead of print).