Having HIV infection raised the risk of lung cancer 70% in a study of more than 110,000 U.S. veterans, even after researchers accounted for the impact of smoking.1 By itself, smoking boosted lung cancer risk more than 6 times. This large study offers perhaps the clearest estimate so far on how HIV infection affects lung cancer risk.
Lung cancer is the most deadly cancer among both men and women in the United States.2 In 2012, more than 226,000 people in the United States were diagnosed with lung cancer and 160,340 died.3 Although smoking is the major cause of lung cancer, this cancer can develop in people who never smoked.
Several previous studies found higher rates of newly diagnosed lung cancer in people with HIV than in the general population. But because of the size or design of these studies, they could not pin down reasons for the higher lung cancer rate in people with HIV.
HIV-positive people may run a higher risk of lung cancer because they tend to smoke more than people without HIV. The earlier studies either did not weigh the impact of smoking on lung cancer risk -- or those studies were limited by (1) how they estimated lung cancer rates, (2) lack of an HIV-negative comparison group, (3) small size, or (4) completion early in the current antiretroviral era, when many more people died of AIDS than they do now.
To address these study limitations, researchers working with the Veterans Aging Cohort Study Virtual Cohort (VACS-VC) conducted this study. The VACS-VC includes veterans with and without HIV. Information on past and current smoking is available for most people in this large study group.
U.S. veterans -- most of them men -- entered the VACS-VC study group from 1997 through 2008. All HIV-positive people in the study had free access to combination antiretroviral therapy, which came into wide use in 1996. For each HIV-positive person in the lung cancer study, researchers selected two HIV-negative veterans, matching them to HIV-positive people by age, gender, race or ethnicity, and Veterans Affairs healthcare site.
The researchers tracked all HIV-positive and negative people until lung cancer diagnosis, death, or the last recorded visit in the VACSVC study. Cases of lung cancer diagnosed after people joined the VACS-VC were identified in the Veterans Affairs Central Cancer Registry. All of these lung cancer cases were confirmed by lab testing.
The VACS-VC team also determined which study participants had other lung diseases, including chronic obstructive pulmonary disease and bacterial pneumonia. The researchers could classify about 80% of study participants as current smokers, former smokers, or people who never smoked.
The investigators used standard statistical methods to identify factors that raised the risk of lung cancer, regardless of any other lung cancer risk factors a person might have.
The study included 37,294 HIV-positive veterans and 75,750 veterans without HIV. Researchers tracked these people for a median of 5.8 years to see if they were diagnosed with lung cancer.
Almost all study participants (98%) were men, 48% were black, 39% white, and 7% Hispanic. Median age of the study group was 46 years. The HIV-positive group included a higher proportion of current smokers than did the HIV-negative group (48% versus 46%), a lower proportion of former smokers (11% versus 15%), and a lower proportion of people who never smoked (20% versus 24%). Only 16% of HIV-positive people were taking combination antiretroviral therapy.
During the study period, 1071 veterans were diagnosed with lung cancer. There were 457 new lung cancer cases in the HIV-positive group and 614 in the twice-larger HIV-negative group. Lung cancer incidence (the new diagnosis rate) was much higher in the HIV-positive group than in the HIV-negative group: 204 versus 119 new lung cancers per 100,000 person-years.
Median age at lung cancer diagnosis was lower in the HIV-positive group (57 versus 59 years).
A comparison of HIV-positive veterans who did and did not get lung cancer revealed these differences:
To identify factors that raised the risk of lung cancer, the researchers performed a statistical analysis that considered the impact of several cancer risk factors: age, gender, race or ethnicity, smoking, and previous diagnosis of chronic obstructive pulmonary disease or bacterial pneumonia. In this analysis, HIV infection raised the risk of new lung cancer 70% -- no matter what other cancer risk factors a person had (Figure 1). Current smokers had more than a 6 times higher risk of lung cancer, and former smokers had a 3 times higher risk. Figure 1 shows all the independent lung cancer risk factors.
Figure 1. HIV infection -- by itself -- raised the risk of lung cancer 1.7 times (70%) in U.S. veterans. Current smoking and former smoking had an even bigger impact on lung cancer risk. COPD, chronic obstructive pulmonary disease; y, year.Figure 1. HIV infection -- by itself -- raised the risk of lung cancer 1.7 times (70%) in U.S. veterans. Current smoking and former smoking had an even bigger impact on lung cancer risk. COPD, chronic obstructive pulmonary disease; y, year.
A separate analysis figured that HIV infection raised the risk of lung cancer 50% in current smokers, 70% in former smokers, and 60% in people who never smoked. These findings confirm that HIV itself boosts the risk of lung cancer regardless of whether a person used to smoke, smokes now, or never smoked.
Finally, the researchers found that most lung cancers in people with HIV and people without HIV got diagnosed at a late stage. Late-stage cancers are the hardest to treat and therefore pose the highest risk of death.
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