Risk factors for lung cancer in people with HIV: smoking vastly outweighs HIV

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Smoking vastly outweighs HIV infection as a risk factor for lung cancer in people with HIV, a large study of US veterans has revealed.

The findings, from the United States Veterans Administration Aging Cohort Study, were presented today at the 17th Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco.

The risk of lung cancer is known to be increased in people with HIV, but until now there has been no clarity about the relative contributions of HIV infection and other risk factors to the likelihood of developing lung cancer.

Glossary

lymphoma

A type of cancer that starts in the tissues of the lymphatic system, including the lymph nodes, spleen, and bone marrow. In people who have HIV, certain lymphomas, such as Burkitt lymphoma, are AIDS-defining conditions.

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

matched

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. 

chronic obstructive pulmonary disease (COPD)

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease that causes obstructed airflow from the lungs. Symptoms include difficulty breathing, cough, mucus (sputum) production and wheezing. It is caused by long-term exposure to irritating gases or particulate matter, most often from tobacco smoking (active or passive).

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.

The Veterans Administration provides care for large numbers of ex-military personnel in the United States, and so provides a large population for the study of HIV-related conditions.

This study took individuals with HIV from the Veterans Aging Cohort Study and matched each one with two individuals of similar age, race and gender.

The cohort was then refined by eliminating all those who had not provided detailed smoking information to a 1999 study of health behaviours, to ensure that detailed baseline information on smoking was available for all participants.

The cohort for analysis comprised 3707 people with HIV (98% male) and 9980 HIV-negative controls, who had been followed for a median of eight years.

The only significant differences between the HIV-positive and HIV-negative groups were in smoking habits (32% of people with HIV smoked daily, compared to 28% of people without HIV infection), history of drug or alcohol abuse (16% vs 10%), and in the incidence of lung cancer during the study (see below).

Investigators used cancer data from cancer registries to ascertain the baseline prevalence and longitudinal incidence of cancer in the cohort.

During a total of 28,500 person years of follow-up, the incidence of lung cancer among patients with HIV was 0.26 per 100 person years. There were 76,800 person years of analysis available for the HIV-negative controls, and their incidence of lung cancer was 0.16 per 100 person years.

After controlling for potentially confounding factors, the investigators calculated that patients with HIV had an 80% increase in the risk of lung cancer (risk ratio, 1.80; 95% confidence interval [CI], 1.28-2.15).

However, current smoking hugely outweighed HIV as a risk factor for lung cancer.

Calculation of the adjusted incidence rate ratio showed an incidence rate of 1.80 for HIV, compared to 9.80 (95% CI 4.4-21.4) in current daily smokers, and an incidence rate of 5.1 (95% CI 2.4-11.2) in people who had stopped smoking at least a year prior to entering the study (so-called distant quitters).

Current occasional smoking was associated with a threefold increase in incidence (3.4, 95% CI 1.0-11.6), while chronic obstructive pulmonary disease (COPD) was associated with an incidence of 1.50 (95% CI 1.1-2.1).

Dr Keith Sigel of Mount Sinai School of Medicine, who presented the findings, told aidsmap: “Stopping smoking is now my second priority at every HIV patient visit and I raise it with every patient at every visit because of the cancer and the cardiovascular risk. Patients with HIV tend to be younger than the average internal medicine patient and so will have many more years of potential smoking exposure if they continue.”

The researchers plan to conduct further analyses to look at the interaction between immunodeficiency and smoking as risk factors for lung cancer, as well as the influence of duration of smoking.

In a second study on cancer and HIV presented at the conference, Dr Michael Silverberg reported that a low CD4 count was associated with an increased risk of a number of non-AIDS defining cancers.

Investigators from Kaiser Permanente in California identified 20,227 HIV-infected individuals and 202,313 HIV-negative controls who were matched for age and sex.

Cancer registries showed that the most common non-AIDS-defining cancers in individuals with HIV were anal, prostate, lung, melanoma, Hodgkin’s lymphoma, oral/throat, and colorectal cancers.

The incidence of cancers in both the HIV-positive and HIV-negative controls was monitored between 1996 and 2007. The cancer risk for those with HIV was stratified by CD4 cell count and viral load, and the results were controlled for potentially confounding factors including age, sex, smoking, alcohol and drug use, hepatitis co-infections, and diabetes.

The risk of cancers of the anus, lung, mouth and throat and Hodgkin’s lymphoma were all increased in patients with HIV.

Compared to the HIV-negative controls, patients with CD4 cell counts below 500 cells/mm3 had an increased risk of anal cancer (p < 0.001) and Hodgkin’s lymphoma.

A CD4 cell count below 200 cells/mm3 significantly increased the risk of lung cancer (p < 0.001) and cancers of the mouth and throat (p < 0.001).

Compared to HIV-negative controls, the risk of anal cancer was especially high for patients with the lowest (<200) CD4 cell counts (hazard ratio [HR], 164.2, p < 0.001).

But the researchers found that even HIV-infected patients with CD4 cell counts above 500 cells/mm3 were more likely than HIV-negative individuals to develop anal cancer (HR = 34.2, p < 0.05) and Hodgkin’s lymphoma (HR = 11.6, p < 0.001).

Further information

You can view abstract 30 and abstract 28 on the official conference website.

You can also view a webcast and slides of this session on the official conference website.

References

Sigel K et al. HIV infection is an independent risk factor for lung cancer. Seventeenth Conference on Retroviruses and Opportunistic Infections, abstract 30, San Francisco, 2010.

Silverberg M et al. Immunodeficiency, HIV RNA levels and the risk of non-AIDS-defining cancers. Seventeenth Conference on Retroviruses and Opportunistic Infections, abstract 28, San Francisco, 2010.

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