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Immune Deficiency Linked to Non-AIDS Cancers in People with HIV

HIV positive people appear more likely than their HIV negative counterparts to develop several types of non-AIDS cancer, and the risk rises with declining immune function, according to a large study of Kaiser Permanente members published in the December 2011 issue of Cancer Epidemiology, Biomarkers, and Prevention.

Several studies over the course of the AIDS epidemic have looked at cancer rates among people with HIV, but results have not been consistent. Some studies have shown elevated rates of certain non-AIDS-defining cancers -- all types except Kaposi sarcoma (KS), non-Hodgkin lymphoma (NHL), and cervical cancer -- but others have found that HIV positive and negative people have similar rates after adjusting for other risk factors.

Michael Silverberg, Donald Abrams, and colleagues compared cancer risk between people with HIV and a demographically similar HIV negative comparison group, adjusting for other cancer risk factors. Both groups were members of the same health care system, allowing for greater similarity than prior comparisons between HIV positive people and general population cancer registries.

The analysis included 20,775 HIV positive and 215,158 HIV negative participants enrolled in Kaiser Permanente (KP) California between 1996 -- the advent of effective antiretroviral treatment -- and 2008. Most were men and a majority were white.

The researchers collected data on incident or new cancer cases, both overall and broken down by recent CD4 T-cell count and HIV RNA viral load. Data were adjusted for patient age, sex, race/ethnicity, smoking, alcohol and drug use, overweight or obesity, calendar period, and KP region.

Results

• As expected, HIV positive people had significantly higher rates of 2 AIDS-defining cancers:

o      Kaposi sarcoma: relative rate (RR) 199, or nearly 200-fold higher;

o      Non-Hodgkin lymphoma: RR 15.

• People with HIV also were at significantly higher risk for certain non-AIDS cancers:

o      Anal cancer: RR 55, or 55 times higher;

o      Hodgkin lymphoma: RR 19;

o      Melanoma skin cancer: RR 1.8, or almost twice as high;

o      Liver cancer: RR 1.8.

• In contrast, HIV positive people had a slightly lower rate of prostate cancer than the HIV negative comparison group (RR 0.8).
• For certain other non-AIDS cancers, there was no significant difference overall between the HIV positive and HIV negative groups:

o      Mouth and throat cancers: RR 1.4;

o      Lung cancer: RR 1.2;

o      Colorectal cancer: RR 0.9.

• When adjusting only for demographics, HIV positive people did have elevated rates of both lung and mouth/throat cancers.
• For KS, NHL, Hodgkin lymphoma, anal cancer, and colorectal cancer, there was a significant trend of increasing risk as recent CD4 count decreased.
• Rate ratios for lung and mouth/throat cancers were significantly elevated for HIV positive people with CD4 counts below 200 cells/mm³.
• Risk of melanoma and liver cancer rose when CD4 count fell below 500 cells/mm³.
• Only KS and NHL showed an association with higher HIV RNA.

Based on these findings, the study authors concluded, "Immunodeficiencywas positively associated with all cancers examined except prostate cancer among HIV-infected compared with HIV-uninfected individuals, after adjustment for several cancer risk factors."

Notably, most of the non-AIDS cancers showing a higher risk for people with HIV are associated with viral infections: Epstein-Barr virus for Hodgkin lymphoma, hepatitis B or C for liver cancer, and human papillomavirus for anal cancer (in fact, the same high-risk HPV strains as AIDS-defining cervical cancer).

These results led the investigators to suggest, "Earlier antiretroviral therapy initiation to maintain high CD4 levels might reduce the burden of cancer in this population."

"Taken together, we believe our results support cancer prevention strategies that combine routine prevention activities, such as smoking cessation, with earlier HIV treatment to help maintain a patient's immune system," Silverberg elaborated in a press release issued by KP.

Investigator affiliations: Kaiser Permanente Northern California, Oakland, CA; Kaiser Permanente Southern California, Pasadena, CA; Mid-Atlantic Permanente Research Institute, Rockville, MD; Kaiser Permanente Northern California, Hayward, CA; Kaiser Permanente Southern California, Los Angeles, CA; Yale School of Public Health and School of Medicine, New Haven, CT; San Francisco General Hospital and University of California San Francisco, San Francisco, CA.

12/20/11

Reference

MJ Silverberg, C Chao, WA Leyden, D Abrams, et al. HIV Infection, Immunodeficiency, Viral Replication, and the Risk of Cancer. Cancer Epidemiology, Biomarkersand Prevention 20(12):2551-2559. December 2011.

Other Source

Kaiser Permanente. Earlier Antiretroviral Therapy might Reduce the Burden of Cancer in those with HIV. Press release. November 22, 2011.