Smoking, not immunodeficiency or lung disease, increases lung cancer risk for patients with HIV

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Cigarette smoking is the single most important risk factor for lung cancer in patients with HIV, Swiss investigators report in the online edition of the British Journal of Cancer.

Smoking was associated with a 14-fold increase in the risk of the malignancy. Unlike some other studies, the Swiss found no evidence that either a low CD4 cell count or a history of AIDS-defining lung disease were associated with lung cancer.

The study also showed the benefits of stopping smoking. The risk of lung cancer was significantly lower for former smokers compared to current smokers.



In a case-control study, a process to make the cases and the controls comparable with respect to extraneous factors. For example, each case is matched individually with a control subject on variables such as age, sex and HIV status. 

AIDS defining condition

Any HIV-related illness included in the list of diagnostic criteria for AIDS, which in the presence of HIV infection result in an AIDS diagnosis. They include opportunistic infections and cancers that are life-threatening in a person with HIV.


Affecting the lungs.



A molecule on the surface of some white blood cells. Some of these cells can kill other cells that are infected with foreign organisms.

“Focusing on ways to help to quit smoking would be effective in reducing lung cancer,” comment the investigators.

Lung cancer is one of the more common non-AIDS-defining cancers seen in patients with HIV. This could be because a large proportion of HIV-positive patients are smokers and studies have shown a consistent relationship between smoking and lung cancer risk for HIV-positive individuals.

However, some research has found a relationship between the malignancy and immune deficiency. In addition, other studies have shown that patients with a history of AIDS-defining pulmonary disease are also at greater risk of lung cancer. Importantly, the associations identified in these studies remained significant after controlling for smoking status.

Given this confusion, investigators from the Swiss HIV Cohort designed a case-controlled study to better identify the factors associated with an increased risk of lung cancer in their patients.

Patients who received HIV care in Switzerland between 1985 and 2010 were eligible for inclusion in the study. Each patient with lung cancer was matched with five patients who did not develop the malignancy. The control patients were of the same age, gender and HIV risk group as the cancer patients.

A total of 68 patients with lung cancer were identified, who were matched with 337 controls.

Most of the patients with cancer were men (79%) and their mean age at cancer diagnosis was 50 years. The overwhelming majority of cases (87%) were diagnosed after effective antiretroviral therapy became available in 1996. The investigators believe that this “may be largely an artefact of the increased survival of HIV-infected persons”, thanks to antiretroviral drugs.

Survival was poor as only 14% of patients were still alive two years after the diagnosis of their cancer.

Prevalence of smoking was high. In all, 85% of lung cancer patients reported that they were current smokers and 6% were former smokers. There was a 50% prevalence of smoking among the control patients, and a quarter had smoked in the past.

There was a strong association between lung cancer and current smoking (OR vs never smoked = 14.4; 95% CI, 3.36-16.6).

“We observed a high prevalence of smoking…and the expected large increased risks for lung cancer among smokers,” the investigators emphasise.

Former smokers had a significantly lower risk of lung cancer compared to current smokers (OR = 0.22; 95% CI, 0.08-0.59).

“The beneficial effects of quitting smoking appear, in relative terms, as important in HIV-infected persons as the general population,” suggest the authors.

Unlike some earlier research, there was no evidence that an AIDS diagnosis with or without pulmonary involvement was associated with lung cancer.

Nor was immunodeficiency associated with an increased risk of lung cancer.

However, a CD4/CD8 ratio lower than 25 within one year of a lung cancer diagnosis had an association of borderline significance with the malignancy (OR = 2.15; 95% CI, 1.00-4.59).

Use of antiretroviral therapy did not increase the risk of lung cancer.

“Our carefully matched case-controlled study…suggests no evidence for a significant effect of HIV-related immunodeficiency on lung cancer risk in this high-risk population,” write the investigators. “None of the classic markers or HIV-related immunodeficiency, including low CD4 cell counts, high viral load nor history of AIDS or AIDS-related pulmonary disease, showed any clear association with lung cancer.”


Clifford GM et al. Lung cancer in the Swiss HIV cohort study: role of smoking, immunodeficiency and pulmonary infection. British Journal of Cancer, online edition. DOI: 10.1038/bjc2011.558, 2011 (click here for the free abstract).