HIV Infection Associated with Increased Risk of Lung Cancer and Other non-AIDS Malignancies

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HIV positive people have about a 70% higher rate of lung cancer compared with a similar HIV negative population, according to a U.S. veterans study described in the May 15, 2012, issue of AIDS. Related studies of cancer risk presented at the 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012) in March also saw higher rates of non-AIDS malignancies among people with HIV.

A number of observational studies have seen increased rates of various non-AIDS-defining malignancies among people with HIV, but data have not been consistent, and it is unclear whether the association is due to biological effects of HIV infection itself, surveillance bias, or traditional non-HIV risk factors such as smoking.

Keith Sigel from Mount Sinai School of Medicine and colleagues compared the incidence of lung cancer between 37,294 HIV positive and 75,750 demographically matched HIV negative people in the Veterans Aging Cohort Study Virtual Cohort and the Veterans Affairs Central Cancer Registry.

Nearly all patients (98%) were men, about half were black, and the mean age was 46 years. Both HIV positive and HIV negative veterans had a high rate of smoking (48% and 46%, respectively), illicit drug use (19% vs 13%), and excessive alcohol use (16% vs 15%); people with HIV were considerably more likely to be coinfected with hepatitis C (35% vs 15%).

The researchers calculated rates of newly diagnosed pathologically confirmed lung cancer by dividing numbers of cases by person-years at risk. Incidence rate ratios (IRRs) were calculated, adjusting for age, sex, race/ethnicity, smoking, and history of bacterial pneumonia and chronic obstructive pulmonary disease (COPD).

Results

·      457 new cases of lung cancer were identified among HIV positive veterans over 5.8 years of follow-up, for anincidence rate of 204 cases per 100, 000 person-years.

·      There were 614 new cases among HIV negative veterans over 7.3 years of follow-up, for a significantly lower incidence rate of 119 cases per 100, 000 person-years.

·      The incidence rate ratio of lung cancer associated with HIV infection remained significant in a multivariate analysis adjusting for smoking and other factors (IRR 1.7, or 70% higher risk).

·      HIV positive current smokers were 6 times more likely to develop lung cancer than non-smokers, while HIV negative smokers were 3 times more likely.

·      19 lung cancer cases in the HIV positive group and 30 in the HIV negative group occurred among people with no reported history of smoking.

·      Stage of lung cancer at the time of diagnosis did not differ between HIV positive and HIV negative patients.

·      The association between HIV and lung cancer risk did not differ according to age, COPD status, or history of bacterial pneumonia.

·      There were also no differences in lung cancer rates according to current CD4 T-cell count, nadir (lowest-ever) CD4 count, HIV viral load, or use of antiretroviral therapy.

"In our cohort of demographically similar HIV-infected and uninfected patients, HIV infection was an independent risk factor for lung cancer after controlling for potential confounders including smoking," the study authors concluded. "The similar stage distribution between the two groups indicated that surveillance bias was an unlikely explanation for this finding."

"In our stratified analysis, we noted a consistent magnitude of association of HIV infection with lung cancer risk across smoking strata, supporting an independent association," the researchers elaborated in their discussion. "Additionally, in a sensitivity analysis where we assumed all HIV-infected former and never smokers were current smokers, HIV infection persisted as a significant risk factor for lung cancer. Nevertheless, we cannot completely rule out the presence of residual confounding by smoking."

Although this analysis found no link between current or nadir CD4 cell count and lung cancer incidence, other research has seen such an effect, and the researchers plan to study these associations more extensively.

CROI Reports

At CROI, Michael Silverberg from Kaiser Permanente Northern California presented his group's findings on age at diagnosis, cancer stage at diagnosis, and survival among 22,081 HIV positive and 230,069 HIV negative age- and sex-matched Kaiser health program enrollees with lung, prostate, anal, and colorectal cancers and Hodgkin lymphoma (HL).

They found that HIV positive individuals were younger on average at diagnosis for lung, anal, and colorectal cancer, but not prostate cancer or HL. Stage at diagnosis was similar regardless of HIV status for all cancer types. People with HIV had significantly lower 5-year survival rates with lung cancer (8% vs 22%, respectively), prostate cancer (84% vs 91%), and HL (65% vs 87%), but not with anal or colorectal cancer.

In a related study, Signe Worm from the D:A:D Study Group reported on an analysis of more than 49,000 HIV positive people receiving care in the modern ART era in 33 countries in North America, Europe, and Australia between January 2004 and January 2010.

The overall rate of non-AIDS-defining cancer was 498 cases per 100,000 person-years. The most common cancers were lung cancer, HL, and anal cancer, with individual incidence rates of 79, 63, and 45 cases per 100,000 person-years, respectively.

The median age at cancer diagnosis was 50 years and the median current CD4 cell count was relatively high at 392 cells/mm3, though the median nadir CD4 count was just 127 cells/mm3. Here, low current and nadir CD4 count, as well as amount of time spent with < 200 cells/mm3, were independent predictors of cancer risk. People whose CD4 counts increased to > 200 cells/mm3 on ART saw a reduction in non-AIDS cancer risk within 2 years.

Researchers for all 3 studies stressed the importance of smoking cessation to reduce cancer rates among people with HIV.

5/18/12

References

K Sigel, J Wisnivesky, K Gordon, et al. HIV as an independent risk factor for incident lung cancer. AIDS 26(8):1017-1025. May 15, 2012.

M Silverberg, C Chao, W Leyden, et al. Cancer Stage, Age at Diagnosis, and Survival Comparing HIV+ and HIV- Individuals with Common Non-AIDS-defining Cancers. 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012). Seattle, March 5-8, 2012. Abstract 903.

S Worm, et al (D:A:D Study Group). NADM and Immunosuppression: The D:A:D Study.19th Conference on Retroviruses and Opportunistic Infections (CROI 2012). Seattle, March 5-8, 2012. Abstract 130.