HIV-positive smokers who had previous lung disease got lung cancer at a 3.5 times higher rate than HIV-negative smokers, according to findings in two large U.S. studies.1 Smoking more cigarettes, older age, and less education further raised the risk of lung cancer.
Since people with HIV started taking combination antiretroviral therapy in the mid-1990s, new diagnoses of certain non-AIDS cancers, including lung cancer (Figure 1), have increased. Several factors may contribute to this increase. First, people with HIV are now living to an older age because they get AIDS illnesses less often, and diseases like lung cancer become more frequent with older age. Second, in the United States and other countries, a higher proportion of people with HIV than without HIV smoke. The Centers for Disease Control and Prevention (CDC) calculates that 42% of HIV-positive people in the U.S. smoke, compared with 21% of the general population.2 And smoking cigarettes is a leading cause of lung cancer. Third, HIV-related inflammation and immune system activation, which affect even people with an undetectable viral load, may contribute to lung cancer. Finally, diseases that affect the lungs and frequently occur in people with HIV, like pneumonia and asthma, may make lung cancer more likely.
Because so many factors may cause or contribute to lung cancer in people with HIV, which factors are most important remains unclear. U.S. researchers working with two large groups of men and women with or without HIV conducted this study with three goals in mind: (1) to compare lung cancer incidence (the new-diagnosis rate) in people with and without HIV, (2) to define lung cancer risk factors, and (3) to determine length of survival with lung cancer in people with HIV.
How the Study Worked
This lung cancer analysis involved HIV-positive or negative women in the Women's Interagency HIV Study (WIHS) and HIV-positive or negative gay or bisexual men in the Multicenter AIDS Cohort Study (MACS), two ongoing studies in which women and men make two study visits a year. WIHS studies women living in six U.S. cities and MACS studies men in four U.S. cities. HIV-negative people in WIHS and MACS have a high risk of HIV infection and are similar to the HIV-positive WIHS and MACS members in behavior, income, race, and other ways.
The lung cancer analysis focused on people in care since they entered WIHS (since 1994) or MACS (since 1984) through September 2011. To see how many people got lung cancer during the study period, researchers checked WIHS and MACS member medical records, confirmed self-reports of lung cancer, state cancer databases, and death certificates. Because all but one lung cancer in WIHS and MACS developed in smokers, the researchers limited the analysis to current and former smokers.
The investigators used accepted statistical methods to compare lung cancer incidence (new diagnoses) in WIHS and MACS members with and without HIV infection. They used standard statistical methods to identify lung cancer risk factors. Their list of possible risk factors included age, race, injection drug use, education, total number of packs smoked per year (pack-years of smoking), previous asthma or pneumonia, and HIV-specific factors like viral load, lowest and highest CD4 count, and antiretroviral therapy. The researchers combined the WIHS and MACS groups to analyze length of survival after a lung cancer diagnosis and factors linked to shorter survival.
What the Study Found
The study included 2549 women who smoked in WIHS, 1875 of them with HIV and 674 without HIV. Of the 4274 men who smoked in MACS, 1860 had HIV and 2414 did not. Two thirds of WIHS women and three quarters of MACS men were younger than 40 when they entered the study. The WIHS group had fewer whites (16.5%) than blacks (58%) or Hispanics (22.5%). The MACS group had more whites (70.2%) than blacks (19.6%) or Hispanics (8.8%). Compared with MACS men, WIHS women had less education and had smoked fewer cigarettes.
During the study period, lung cancer developed in 37 WIHS women, including 31 women with HIV and 6 without HIV. Lung cancer developed in 23 MACS men, 15 of them with HIV and 8 without HIV. Lung cancer developed significantly more often in WIHS women than in MACS men. Lung cancer incidence was 119 cases per 100,000 person-years in people with HIV versus 45 per 100,000 person-years in people without HIV. A rate of 119 per 100,000 person-years means lung cancer developed in 119 of every 100,000 people every year. This difference in lung cancer incidence between people with versus without HIV is statistically significant, meaning the difference cannot be explained by chance.
Statistical analysis that considered several lung cancer risk factors at the same time identified four factors that raised the risk of lung cancer in smokers with HIV versus smokers without HIV -- older age, less education, more pack-years smoking, and a previous diagnosis of AIDS pneumonia (Figure 2). Compared with HIV-negative smokers, HIV-positive smokers who had AIDS pneumonia in the past had more than a 3.5 times higher risk of lung cancer. These four factors raised the risk of lung cancer regardless of whatever other risk factors a person had. And they raised the lung cancer risk in both WIHS women and MACS men. When the researchers conducted a separate analysis involving only WIHS women, that analysis linked a previous asthma diagnosis to a 2.4-fold higher lung cancer risk.
Next the researchers assessed survival with lung cancer in 56 WIHS women and MACS men who had medical records available after their lung cancer diagnosis. Forty-five of these 56 people (80%) died during the study period. WIHS women with lung cancer survived for a median of 9.5 months and MACS men survived for a median of 6.2 months.
Statistical analysis that evaluated several death risk factors identified two risk factors linked to survival with lung cancer in the combined WIHS and MACS groups of people with and without HIV. First, being diagnosed with lung cancer in 2001-2011 versus 1984-1994 was linked to a 77% lower risk of dying after a lung cancer diagnosis. And second, having a history of injecting drugs tripled the risk of dying after a lung cancer diagnosis. Finally the researchers limited the survival analysis to the 42 HIV-positive people diagnosed with lung cancer. In this analysis a lowest-ever CD4 count below 200 was linked to a 2.55 times higher risk of death after lung cancer diagnosis.
What the Results Mean for You
This large and long study in U.S. women and men found that HIV-positive current and former smokers have a higher rate of newly diagnosed lung cancer than current and former smokers without HIV. The study also pinpointed certain factors that raised the risk of lung cancer -- including smoking more cigarettes and having HIV-related pneumonia in the past.
Everyone in this study -- women and men with and without HIV -- smoked at some point in their life. There is no question that smoking causes lung cancer. This study's finding that smokers with HIV run a higher risk of lung cancer than smokers without HIV should give HIV-positive smokers extra motivation to quit. Another recent study reviewed in this issue found that smoking boosts the risk of heart attacks in HIV-positive people more than in HIV-negative people.3 Smoking can also cause other lung diseases, other cancers, stroke, and bone thinning that could lead to broken bones (a growing problem in people with HIV.)
This new study found that having AIDS pneumonia in the past explained about two thirds of HIV's negative impact on lung cancer risk. Smokers who had an AIDS pneumonia -- either Pneumocystis pneumonia or bacterial pneumonia -- or who had a lung disease, such as asthma, should try extra hard to quit.
Another important finding of this study is that most people who got lung cancer died within a year of their lung cancer diagnosis. Half of men who got lung cancer died in 6 months, and half of women who got lung cancer died in 9.5 months. But the study also made a hopeful finding about survival after lung cancer diagnosis: Survival with lung cancer has improved in recent years in people with HIV. The researchers suggested three possible reasons for this improvement: (1) more lung disease testing in people with HIV, leading to earlier detection of lung cancer and thus a greater chance of successful treatment, (2) more frequent use of better treatments for lung cancer in people with HIV, and (3) wider use of stronger antiretroviral combinations before, during, and after lung cancer treatment, which can prevent other deadly diseases.
Quitting smoking is the single most important thing smokers can do to avoid lung cancer -- as well as several other deadly diseases. Some longtime smokers can make up their minds to quit and never light up another cigarette. Many others have a hard time quitting. Any HIV-positive smoker should know two things: (1) Your HIV provider can discuss several strategies that have helped many people quit -- including nicotine replacement and other treatments. And your provider can suggest which strategies may be the best options for you. "Decision Tree Guides Selection of Smoke-Ending Medication for People With HIV" in this issue describes one potentially successful strategy.4 (2) Many people who try to quit and fail finally do manage to quit after two, three, or more attempts. There are more former smokers in the United States than current smokers.5
- Hessol NA, Martínez-Maza O, Levine AM, et al. Lung cancer incidence and survival among HIV-infected and uninfected women and men. AIDS. 2015,29:1183-1193.
- Mdodo R, Frazier EL, Dube SR, et al. Cigarette smoking prevalence among adults with HIV compared with the general adult population in the United States: cross-sectional surveys. Ann Intern Med. 2015;162:335-344.
- Rasmussen LD, Helleberg M, May MT, et al. Myocardial infarction among Danish HIV-infected individuals: population-attributable fractions associated with smoking. Clin Infect Dis. 2015;60:1415-1423.
- Cropsey KL, Jardin BF, Burkholder GA, et al. An algorithm approach to determining smoking cessation treatment for persons living with HIV/AIDS: results of a pilot trial. J Acquir Immune Defic Syndr. 2015;69:291-298.
- The Health Consequences of Smoking -- 50 Years of Progress: A Report of the Surgeon General. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2014.