Lung Cancer: An Emerging Epidemic in the human immunodeficiency virus-Infected Population

Abstract

As opportunistic infections and acquired immune deficiency syndrome (AIDS)-related cancers are decreasing in the human immunodeficiency virus (HIV)-infected population since the advent of highly active antiretroviral therapy (HAART), new causes of morbidity and mortality are emerging, such as cardiovascular diseases and non-AIDSdefining cancers (NADCs).1–4 The general aging of the HIV-infected populations in resource-rich settings, because of an increasing life expectancy approaching that of the general population in some successfully treated groups, also explains this shift to nonopportunistic diseases.5,6 In resource-rich setting studies, lung cancer has the highest incidence rate of all NADCs,3,7 and despite the advent of HAART, its incidence rate remains increased in comparison with the non-HIV-infected population. The review by Pakkala and Ramalingam8 focuses on epidemiological, clinical, and management of lung cancers in HIV-infected patients and helps us to disentangle future perspectives of research. This review underscores the increased incidence and the clinical particularities of lung cancer in the HIV-infected population in comparison with the HIV-negative counterparts, including an increased proportion of advanced stages III and IV and young age at diagnosis, as well as its dismal prognosis. The reasons of an increased incidence in the rate of lung cancer in the HIV-infected population in comparison with their uninfected counterparts have been approached in this review. One factor is the increased prevalence of smoking in the HIV-infected populations: in different observational cohorts, the rate of chronic smoking history has been evaluated as more than 50%, outnumbering the proportion of smokers in the general population.9 However, this characteristic, although essential in the triggering of lung cancer in the HIV-infected population, is insufficient to completely explain the increased incidence, because multivariate studies adjusted on smoking status, age, and gender have found a persistent increased risk of lung cancer.10–12 The most important factor explaining increased incidence of lung cancer in HIVinfected patients is probably the intensity and duration of immune deficiency. Grulich et al.13 found a significantly and similar standardized increased ratio in lung, trachea, and bronchus cancer in comparison with the general population in HIV-infected population and solid organ transplant recipients in a meta-analysis of population-based cohorts (respective standardized increased ratio of 2.72 [1.91–3.87] and 2.18 [1.85–2.57]), immunodeficiency being the only common factor between these two populations. It is now well established that the intensity of CD4 depletion is an important factor. The Clinical Epidemiology Group of the FHDH-ANRS CO4 cohort correlated risk of lung cancer with the latest levels of CD4 strata7 in more than 52,278 subjects and showed a progressive increase of incidence for each lower strata of CD4: odd ratios ranged from 8.5 (4.3–16.7) for the CD4 strata of 50 cells/ l to 2.2 (1.3–3.6) for the CD4 strata of 350 to 500 cells/ l