HIV is an independent risk factor for lung cancer

Infection with HIV is an independent risk factor for lung cancer, according to the results of a large US study published in the online edition of AIDS.

Investigators from the US Department of Veterans Affairs found that HIV increased the relative risk of lung cancer by 70%, even after controlling for other potential risk factors.

“We found that HIV infected Veterans had a significantly higher incidence of lung cancer than uninfected Veterans,” write the authors. “HIV infection was an independent risk factor for lung cancer after controlling for potential confounders including smoking.”

Although it is rare, lung cancer is an increasingly important cause of death in patients with HIV. The exact reasons for this are unclear. The immune damage caused by the virus may have an important role. Moreover, it is well known that there is a high prevalence of smoking among HIV-positive people. In addition, the intensive medical monitoring that should form an integral part of HIV care could mean that lung cancer is more likely to be detected in people with HIV than in uninfected individuals. 

Investigators from the Department of Veterans Affairs – a major provider of free HIV care in the US – wanted to establish a clearer understanding of the possible association of HIV with this malignancy.

They therefore studied data from 37,294 HIV-positive individuals, which was matched with the medical records of 75,750 HIV-negative people. The participants all received care after the introduction of effective antiretroviral therapy. The investigators calculated the incidence of lung cancer for the two groups, and also undertook a series of analyses to see if HIV was an independent risk factor for the malignancy. These analyses took into account other possible risk factors, such as age, gender, smoking and history of other lung diseases.

Median duration of follow-up was 5.8 years for the HIV-positive people and 7.3 years for the HIV-negative individuals (p < 0.001).

The patients had a mean age of 46 years and 98% were men. Approximately half were black.

The HIV-infected participants were more likely to be current smokers (48 vs 46%), to misuse drugs (19 vs 13%) or alcohol (16 vs 15%), to be co-infected with hepatitis C (35 vs 15%) and to have a previous history of bacterial pneumonia (5 vs 1%; all comparisons, p < 0.001).

A total of 457 new cases of lung cancer were identified in the HIV-positive patients and 614 cases among the HIV-negative individuals. The incidence of the malignancy was therefore 204 cases per 100,000 person-years for the HIV-infected patients and 119 cases per 100,000 person-years for the HIV-negative people in the control group. Incidence was therefore some 70% higher in the HIV-positive participants (IRR = 1.7; 95% CI, 1.5-2.0).

Next, the investigators compared the characteristics of the HIV-positive and HIV-negative participants who developed lung cancer. They found that those with HIV were older (51 vs 45 years), were more likely to be white (47 vs 38%), had a higher prevalence of current smokers (57 vs 48%), had increased rates of chronic obstructive pulmonary disease (11 vs 4%) and were also more likely to have a been diagnosed with bacterial pneumonia (8 vs 5%; comparisons, p < 0.001 or p = 0.01).

After taking into account other factors associated with lung cancer risk, the investigators found that HIV remained a significant, independent risk factor for the malignancy (IRR = 1.7; 95% CI, 1.5-1.9, p < 0.001).

Other risk factors included older age, being a current or former smoker, having a history of chronic obstructive lung disease (all p < 0.001), and a history of bacterial pneumonia (p = 0.007).

Sensitivity analyses, one of which purposefully over-estimated the prevalence of HIV-positive participants who were current smokers, confirmed the significant association between infection with HIV and an increased risk of lung cancer (IRR = 1.2; 95% CI, 1.1-1.4).

Cancer stage at the time of diagnosis was similar for the HIV-positive and HIV-negative participants. “The increased incidence of lung cancer among the HIV infected patients does not appear to be explained by more vigilant surveillance,” comment the investigators.

Although they found no significant association between lung cancer risk and current CD4 cell count or viral load, the researchers note that such associations have been found in other studies. They write: “For the purposes of understanding the relationship between immunodeficiency and lung cancer risk among HIV infected patients, we plan to conduct more sophisticated analyses with time-updated modeling of CD4 cell count.”

The authors believe their findings may actually under-represent both the incidence and risk of lung cancer for patients with HIV. They therefore conclude: “Additional investigations are required to understand the mechanisms by which HIV infection may increase the risk for lung cancer.”