People with HIV Develop Non-AIDS Cancers Earlier and More Often, despite Antiretroviral Therapy

		SUMMARY: Non-AIDS-defining cancers continue to increase in people with HIV even if they are taking antiretroviral therapy (ART), researchers reported at the XVIII International AIDS Conference (AIDS 2010) last month in Vienna. According to another presentation, HIV positive people were more likely to develop non-AIDS cancers compared with the general population -- especially malignancies with infectious causes -- and did so at a younger age on average.

By Liz Highleyman

Research over the past several years has revealed elevated rates of non-AIDS-defining cancers -- that is, all malignancies except Kaposi's sarcoma, non-Hodgkin lymphoma (NHL), and cervical cancer -- in the HAART era, though different studies have produced conflicting findings concerning which specific cancers occur more often.

Rising Cancer Rates

In the first study presented at AIDS 2010, Eric Engels from the National Cancer Institute and colleagues estimated the number of cancers occurring over time among people with HIV in the U.S.

Antiretroviral therapy has greatly reduced incidence of AIDS-defining cancers, the researchers noted as background, but as HIV positive people survive longer, there is more time for development of progressive cancers that typically occur at older ages.

Investigators compared rates of cancer among HIV positive and HIV negative individuals. Cancer incidence rates were determined by linking Centers for Disease Control and Prevention (CDC) HIV/AIDS data and cancer registries in 15 U.S. areas.

For people with AIDS, cancer numbers were estimated for 1991-2005 by applying cancer incidence rates to the U.S. population with AIDS based on year, age, sex, race/ethnicity, HIV transmission category, and time since AIDS diagnosis. For HIV positive people without AIDS, cancer counts were estimated for 2004-2007 by applying overall cancer rates for 1998-2005 to HIV cases from 34 states with confidential name-based HIV reporting since 2004.

Results

	The number of people with AIDS in the U.S. increased from 93,802 (8% of them age 50 or older) in 1991 to 399,762 (29% age 50 or older) in 2005.
	During 1991-2005, there were 76,558 total cases of cancer in this population.
	AIDS-defining cancers -- mainly Kaposi sarcoma and NHL -- declined from 7284 cases in 1993 to 1736 cases in 2005.
	In contrast, non-AIDS-defining cancers increased over time, from 416 reported cases in 1991 to 2437 cases in 2005.
	Cases of anal cancer (18 in 1991 vs 358 in 2005) and prostate cancer (10 vs 123, respectively) rose steeply, with increases in both absolute numbers and rates of occurrence.
	The absolute number of cases of lung cancer (112 in 1991 vs 478 in 2005) and Hodgkin lymphoma (72 vs 169, respectively) also rose, but rates remained relatively stable.
	During 2004-2007 in the 34 states with name-based reporting, 4388 cases of cancer occurred among people with HIV but not AIDS.
	These included 892 cases of lung cancer, 381 cases of anal cancer, and 327 cases of Hodgkin lymphoma.

Based on these findings, the researchers concluded, "Dramatic increases in non-AIDS-defining cancers among persons with AIDS are driven by growth and aging of the AIDS population, and rising incidence rates for some cancers."

"Cancer prevention and treatment in HIV-infected persons are increasingly important," they added.

Cancer at Younger Age

The second study, presented by Minh Ly Nguyen from Emory University School of Medicine, evaluated the age at cancer diagnosis and standardized incidence ratios (SIRs) for various cancers among people with HIV at an Atlanta clinic. These were then compared rates for the general population based on data from the CDC's Surveillance, Epidemiology and End Results (SEER) cancer registries, matched for age, sex, and race/ethnicity.

This retrospective analysis included data from 8300 patients seen at a Ryan White-funded urban HIV clinic in Atlanta between 2000 and 2007. About 75% were men, most were black, and the average age was about 39 years. The researchers did not have adequate data on potential risk factors such as smoking.

Results

	512 patients received a cancer diagnosis during the study period:
	320 AIDS-defining cancers (most commonly Kaposi's sarcoma); 192 non-AIDS malignancies, including:   40% lung cancer; 24% anal-rectal cancer; 22% head and neck cancer; 18% prostate cancer; 16% Hodgkin lymphoma; 11% breast cancer; 10% liver cancer.
	Incidence rates for most non-AIDS cancers -- with the exception of prostate cancer and breast cancer -- were significantly higher for people with HIV compared with the general population:
	Anal-rectal cancer: SIR 67.6, or nearly 68 times higher incidence; Hodgkin lymphoma: 19.7; Liver cancer: 9.5; Head and neck cancer: 8.7; Lung cancer: 4.5; Breast cancer: 1.1, not a significant difference; Prostate cancer: 0.55, or a 45% lower incidence.
	Except for Hodgkin lymphoma, these cancers were diagnosed on average 10-15 years earlier in HIV positive people compared with the general population:
	Prostate cancer: 53 years for HIV positive vs 64 years for HIV negative; Lung cancer: 52 vs 66 years, respectively; Head and neck cancer: 51 vs 61 years, respectively; Breast cancer: 45 vs 58 years, respectively; Liver cancer: 44 vs 60 years, respectively; Anal-rectal cancer: 41 vs 55 years, respectively; Hodgkin lymphoma: 40 vs 42 years, respectively.
	Average CD4 cell counts at the time of cancer diagnosis were 263 cells/mm3 for men and 344 cells/mm3 for women;
	Mean nadir or lowest-ever CD4 counts were 129 cells/mm3 for men and 214 cells/mm3 for women.
	Based on available data, about half the HIV patients were not on ART and only about 15% had undetectable viral load at the time of cancer diagnosis.

These findings led the investigators to conclude, "Many non-AIDS-defining cancers occur at an increased rate compared to the general population and at an earlier age."

This was particularly true for cancers with an infectious cause, including anal cancer (caused by human papillomavirus), Hodgkin lymphoma (linked to Epstein-Barr virus), and liver cancer (often due to chronic hepatitis B or C).

"Cancer screening in HIV-infected patients should be considered at an earlier age than in the general population," Nguyen recommended.

Investigator affiliations:

Shiels study: National Cancer Institute, Rockville, MD; Centers for Disease Control and Prevention, Atlanta, GA.

Nguyen study: Emory University School of Medicine, Atlanta, GA; Grady Health Systems, Atlanta, GA; Rollins School of Public Health, Global Health & Epidemiology, Emory University, Atlanta, GA.

8/17/10

References

Shiels, R Pfeiffer, M Gail, E Engels, and others. The burden of cancer among HIV-infected persons in the U.S. population. XVIII International AIDS Conference (AIDS 2010). Vienna, July 18-23, 2010. Abstract WEAB0101.

ML Nguyen, A Sumbry, D Reddy, and others. Earlier age at cancer diagnosis and increased incidence of non-AIDS defining cancers in patients with advanced HIV infection. XVIII International AIDS Conference (AIDS 2010). Vienna, July 18-23, 2010. Abstract WEAB0105.

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