Previous AIDS-related pulmonary disease associated with lung cancer risk for people with HIV

AIDS-related pulmonary disease is a major factor in the increased risk of lung cancer seen in people with HIV, investigators from the United States report in AIDS. The study compared lung cancer incidence rates and survival time between HIV-positive and HIV-negative individuals.

“We found that HIV infection alone was not an independent risk factor for lung cancer, but the amount of cigarette smoking over time and prior AIDS pneumonia among HIV-infected adults were major contributors for the development of lung cancer,” comment the authors.

The incidence of AIDS-related cancers (especially Kaposi’s sarcoma and non-Hodgkin’s lymphoma) has declined markedly since the introduction of effective antiretroviral therapy (ART). However, several studies have reported increased incidence of lung cancer among people with HIV since the advent of ART. It is unclear if this increase is simply due to the higher rates of smoking observed in people with HIV. There is some evidence that immune suppression associated with untreated HIV infection and pulmonary damage caused by AIDS-related infection such as PCP pneumonia and recurrent bacterial pneumonia may also be important risk factors for lung cancer.

Given this uncertainty, investigators designed a study to determine the incidence, risk factors and survival time for lung cancer among individuals enrolled in two longitudinal cohort studies of HIV infection, one involving women (Women’s Interagency HIV Study [WIHS]) (n=2549), the other men (Multicenter AIDS Cohort Study [MACS]) (n=4274). Both cohorts include a comparison population of HIV-negative at-risk individuals.

Patients were followed until September 2012. A total of 60 incident lung cancers (46 in people with HIV, 14 in HIV-negative participants) were recorded among cohort participants.

The average age at lung cancer diagnosis was 52 years among women with HIV and 51 years among HIV-negative women. For men, the average age of diagnosis was 50 years for those with HIV and 54 years for HIV-negative patients. All were smokers.

Overall, lung cancer incidence was significantly higher among women (151.8 per 100,000) than men (50.7 per 100,000)(p < 0.001). Incidence was also higher among patients with HIV (119 per 100,000) compared to HIV-negative individuals (45 per 100,000)(p = 0.001).

All cases of lung cancer occurred in smokers. Thirty-one of the 60 cases occurred in people who had accumulated at least 30 years of smoking history. (A pack year is equivalent of smoking 20 a day for one year). Ten or more pack years of smoking was found to be significantly associated with the incidence of lung cancer in multivariable analysis.

HIV infection was not associated with a significantly increased risk of lung cancer when the two cohorts were analysed separately. It was only when the two cohorts were combined that HIV became significantly associated with lung cancer risk (IRR = 2.64; 95% CI, 1.43-5.21).

After controlling for potential confounders, analysis of the combined cohorts showed that factors independently associated with lung cancer were older age, less education, smoking intensity and a previous diagnosis of AIDS-related pneumonia.

“We found that approximately two-thirds of the effect of HIV infection was explained by a diagnosis of prior AIDS pneumonia,” comment the authors. “Inflammatory pulmonary disease and infections have been shown to play a role in the development of lung cancer in the general population, and this has also been observed among HIV-infected individuals, particularly in association with recurrent pneumonia.”

Of the 31 lung cancers diagnosed among women with HIV, 20 had a previous AIDS diagnosis, 14 of which involved an AIDS-related pneumonia. Of the 15 cases of lung cancer among men with HIV, six involved individuals with a previous AIDS diagnosis, three of which involved pneumonia.

Survival data were available for 56 patients, and during follow-up 45 of these individuals died. Mean survival time for women was 9.5 months, whereas men survived for an average of six months. Analysis of all 56 patients showed that the only factor associated with longer survival was diagnosis after 2001. A history of injecting drug use was associated with shorter survival.

The investigators then restricted their analysis to the 42 lung cancer patients with HIV. The only HIV-related factor independently associated with lung cancer survival was a nadir CD4 count below 200 cells/mm³ (HR = 2.55; 95% CI, 1.09-5.95).

“Our data suggest that pulmonary damage and inflammation associated with HIV infection may be causative for the increased risk of lung cancer,” conclude the investigators. But they also noted, “Encouraging and assisting younger HIV-infected smokers to quit and sustain cessation of smoking is imperative to reduce the lung cancer burden in this population.”