We found a substantially increased risk of lung cancer among both HIV-infected and at-risk uninfected women compared with population-based expectations. A possible explanation is the high rate of cigarette smoking in WIHS women, reported by approximately two thirds, including all women diagnosed with incident lung cancer. Several prior reports have also documented a strong history of tobacco exposure in their HIV-infected patients who developed lung cancer.6,8,9,11–13
As previously noted,23
we found that WIHS women were almost twice as likely to smoke as age- and race-matched women, studied as part of NHANES III.17–19
While multiple other behavioral and demographic differences between WIHS and NHANES III women were found, only smoking was significantly associated with incident lung cancer. Thus, when compared to population-based controls, any increase in the incidence of lung cancer among HIV-infected women could be explained by differences in history of tobacco exposure.
When comparing lung cancer incidence rates between HIV-infected women in the WIHS and the internal group of HIV-uninfected women, no differences were apparent. Of importance, all women with lung cancer had strong histories of tobacco exposure, thus serving to explain the equivalent increase in lung cancer among both HIV-infected and uninfected women, when compared with population-based expectations. Of note, both HIV-infected and -uninfected WIHS participants were statistically more likely to smoke than the NHANES III/US female population. Nonetheless, HIV-uninfected women with lung cancer had smoked for 25 and 30 PYs, while those infected with HIV had 10 to 20 PY smoking history. It is possible that HIV may accelerate the development of lung cancer.
Several studies have shown a significant increase in lung cancer among HIV-infected patients after the introduction of HAART.6,8,9
The remarkable prolongation in survival due to HAART may have allowed these individuals to live long enough to develop lung cancer. However, we found no difference in the incidence of lung cancer among HIV-infected women in the pre-HAART versus HAART eras. A recent study of 54,780 HIV-infected patients also failed to demonstrate an increase in lung cancer incidence in the HAART era,24
suggesting that the excess risk of lung cancer is not related to use of antiretroviral therapy per se, but rather to other factors, such as pack-years of smoking, in an aging population.
A significant increase in the risk of death due to lung cancer was reported among HIV-infected IDUs,8
studied as part of the AIDS Link to the Intravenous Experience Study (ALIVE); 26 of 27 patients had history of smoking. After adjusting for smoking status and other variables, HIV infection was found to be independently associated with an increased risk of lung cancer death. Our data indicate that HIV, per se, was not a risk factor for initial development of lung cancer. While it is plausible that HIV-infected patients with lung cancer may be more likely to succumb to the malignancy than their HIV-uninfected counterparts, still, this study, and that from ALIVE actually address different issues. It is also possible that lifestyle factors related to IDU may have increased the risk of pre-existing pulmonary disease, possibly predisposing to lung cancer. In this regard, the incidence rate for lung cancer among former or current IDUs in the WIHS was more than twice that of participants without history of IDU, although this difference was not statistically significant.
Similar to this study, locally extensive or metastatic lung cancer has been reported at diagnosis in both pre-HAART12
and HAART eras,25
despite improvements in immunity associated with HAART. Delays in initial diagnosis of lung cancer among HIV-infected persons may explain the disseminated nature of disease.25
Alternatively, factors related to HIV itself, or to the abnormal immunologic milieu associated with HIV may be operative.
Several studies have reported that adenocarcinomas occur more commonly than expected in HIV-infected individuals,4,12,26–29
while others have not.6,13,30
Our data demonstrate an equivalent distribution of pathologic types. Brock and colleagues25
noted a change in the pathologic spectrum of lung cancer among 92 HIV-infected patients, when comparing pre-HAART and HAART eras, with 48% of all cancers diagnosed as adenocarcinoma in both time periods, while squamous cell carcinoma increased from 10% to 21%.
The WIHS study followed a large cohort prospectively for up to 12 years, and all cancer diagnoses were confirmed. However, details of treatment or response were not available. Furthermore, despite our large database of more than 3,500 women and 25,000 PYs of follow-up, the small number of incident lung cancers limited the statistical power. Nonetheless, a prospective comparison between HIV-infected women, and HIV-uninfected women with similar lifestyles was possible, augmenting the study design. Further, the careful documentation of tobacco exposure, and the ability to compare our data with behavioral data from age- and race-matched US women (NHANES III) allowed evaluation of the potential role of cigarette smoking as a cause for the increase in lung cancer among WIHS women.
We have demonstrated that WIHS participants, whether HIV-infected or at-risk but uninfected, have a significantly increased risk of lung cancer when compared with the rates expected in the general population, while no difference in lung cancer rates among HIV-infected versus uninfected women was seen. Of importance, both HIV-infected and -uninfected WIHS participants were significantly more likely to have smoked than the NHANES III/US female population. All WIHS women with lung cancer had history of smoking, and the risk of cancer increased with increasing smoking exposure. The development of lung cancer among HIV-infected women appears very strongly correlated with tobacco exposure. As such, the development and implementation of smoking cessation programs aimed at HIV-infected persons will be of increasing importance. The precise role of HIV infection, per se, in terms of the development or progression of lung cancer awaits further clarification.