Examining Lung Cancer Risk Factors in HIV-Positive US Veterans

Low CD4/CDE8 ratio and a history of bacterial pneumonia heighten the risk for lung cancer in an HIV-positive population.

Individuals who are HIV-positive are known to be at higher risk of lung cancer, the most common non-AIDS-defining cancer, but until recently there was a dearth of information about the role that immune function plays in this risk. A recent study conducted by researchers from medical schools and Veterans Affairs medical centers across the United States is shedding some light on the specific systemic processes that result in a higher incidence of lung cancer and worse outcomes in the HIV-positive population.

The team examined a minimum of three years of health data from 21,666 veterans with HIV who were part of the Veterans Aging Cohort Study, and then looked at cancer registry data to identify cases of lung cancer that arose in that population. They identified 277 lung cancer cases among the study participants during the time they were being tracked in the Veterans Aging Cohort Study. After accounting for risk factors such as smoking, age, and chronic obstructive pulmonary disease (COPD), they found that lung cancer was more prevalent among the HIV-positive veterans whose health data revealed one or more of several notable conditions. One of these was a low CD4 cell count. CD4 cells are also known as T helper cells, and they play a big role in fighting off infection. Another important marker for lung cancer was a low CD4/CD8 ratio, or the ratio between two kinds of white blood cells that protect against cancer and other invaders. The lung cancer patients also tended to have high HIV RNA concentration in their blood, signifying a higher number of HIV particles circulating in the body. Finally, recurrent bacterial pneumonia was a marker for lung cancer.

“Our study...illustrates that lung cancer is an important source of morbidity and mortality for HIV-infected persons in the antiretroviral era, and demonstrates some unique risk factors that may be responsible for some of the excess of lung cancer cases observed in persons with HIV,” says Keith Sigel, MD, MPH, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai, New York, and an author of the study. “We found that a low CD4/CD8 ratio, a previously unidentified risk factor for lung cancer, was the most robust immunologic predictor of lung cancer in HIV-infected persons.”

Bacterial pneumonia history also emerged as a strong risk factor for lung cancer. According to the scientists, HIV itself increases the risk of developing pneumonia. Once pneumonia is present, it’s possible that the inflammation in the lungs heightens the cancer risk, although the researchers say this is difficult to prove. Early introduction of antiretroviral therapy and/or preventive pneumococcal vaccination could significantly reduce the risk of lung cancer.

Unfortunately, HIV negatively affects lung cancer patients’ ability to recover. “In most large studies of lung cancer in HIV-infected persons, outcomes have been worse compared to uninfected persons,” says Dr. Sigel. “This appears to be largely related to increased treatment disparities and lung cancer treatment intolerance. Our cancer research group with the Veterans Aging Cohort Study is actively studying lung cancer outcomes and working to identify ways of improving lung cancer treatment and treatment outcomes in HIV-infected persons.”

In addition to recommending that patients quit smoking, providers may want to consider imaging tests, particularly the CT scan. “Lung cancer screening with low dose computed tomography has been shown to reduce lung cancer mortality in HIV-uninfected persons,” says Dr. Sigel. “There is limited data evaluating this screening test in persons with HIV, but Dr. Alain Makinson’s research group in France found that screening safely identified early-stage cancers in a cohort of [about] 400 HIV-infected smokers. Therefore, given the higher risk of lung cancer associated with HIV, there is promising early data to suggest that screening may be a valid way of monitoring high-risk HIV-infected smokers for lung cancer.”

Laurie Saloman, MS, is a health writer with more than 20 years of experience working for both consumer and physician-focused publications. She is a graduate of Brandeis University and the Medill School of Journalism at Northwestern University. She lives in New Jersey with her family.