Lung cancer in HIV-infected patients

Abstract

Our objective was to determine the prevalence and characteristics of lung cancer (LC) in HIV patients and compare them with LC patients from the general population. All HIV patients diagnosed at three hospitals in Malaga (southern Spain) who developed LC during January 1989-June 2012 were reviewed. They were compared with a sample of patients with LC taken from the Pneumology and Oncology Department of the Hospital Virgen de le Victoria (Malaga) during the same period. Of the 4721 HIV patients (83% men) followed-up during the study period, 61 (1.29%) developed LC: 82% were men, mean age 48 years, all except two were smokers, 47.5% had a prior lung infection, and the median CD4 count was 237 cells/mm³. Forty (65.5%) patients were on antiretroviral therapy at LC diagnosis (70% had an undetectable viral load). The HIV-negative group was older at diagnosis, contained fewer active smokers, had a greater frequency of the squamous cell carcinoma histological subtype and fewer cases of adenocarcinoma. Presentation was advanced in both groups and the median survival of HIV patients was three months. LC is a common tumour in HIV patients. It affects men and women equally, with a history of smoking and often a prior opportunistic lung disease. Affected patients are often immunosuppressed and have had an AIDS-related diagnosis.

Keywords

HIV AIDS lung cancer malignancies

Introduction

Lung cancer (LC) is the most common cause of cancer mortality worldwide for both men and women, accounting for approximately 1.2 million deaths each year.¹ In Spain, as in the rest of the developed world, certain changes are taking place, such as a greater incidence of LC in women, though the poor prognosis remains.² Among HIV-infected persons, LC is the third most common malignancy, preceded only by Kaposi’s sarcoma and non-Hodgkin lymphoma.^3–6 Moreover, epidemiologic data suggest that the risk of LC is two to four times greater in HIV-infected persons than in the general population, even after adjusting for other factors such as smoking intensity and duration.^7–11 Given the good prognosis associated with HIV infection after the widespread use of antiretroviral therapy¹² and the high prevalence of smokers in cohorts of HIV-infected patients, an increase is foreseeable in neoplasms, including LC, in this population.¹³

The aim of this study was to determine the prevalence and characteristics of LC in an HIV-infected population and compare the results with a group of LC patients from the general population.

Patients and methods

We undertook an observational, retrospective study involving three hospitals in the province of Malaga in southern Spain. We reviewed the clinical histories of all the HIV-infected patients diagnosed at these centres who developed LC between January 1989 and June 2012. All the patients had to have a confirmed infection with HIV and a histological diagnosis of LC. Patients were excluded if their cancer was diagnosed before the diagnosis of their HIV infection. Epidemiological, clinical and immunovirological data were gathered as well as the characteristics of the tumour and its course. This HIV-infected population was compared with a sample of patients with LC taken from the clinical histories of the Pneumology and Oncology Department of the Hospital Virgen de le Victoria (Malaga) during the same period. None of these latter patients had a diagnosis of HIV infection in their histories. The continuous variables are expressed as the median (interquartile range [IQR]) and the categorical variables as the number of cases (percentage). To calculate the prevalence of LC in the HIV-infected patients, the denominator was composed of those patients who were under follow up or who had died, excluding patients lost to follow up. The survival rates were calculated with Kaplan–Meier curves. The data were analysed with SPSS version 17.0 (SPSS, software, Chicago, IL, USA).

The study was approved by the Ethics and Research Committee of the Hospital Virgen de la Victoria. At all times the confidentiality of the participants was respected, in accordance with Spanish Organic Law 15/1999 on Personal data.

Results

Of the 4721 HIV-infected patients (83% men) followed up during the study period, 61 developed LC, giving a prevalence of 1.29% (95% CI, 0.96–1.61). Of these 61, 82% were men and the male-to-female rate was 1:1. The mean age at diagnosis of the LC was 48 years. All except two were active smokers and almost half had experienced a prior lung infection. At the time of diagnosis of LC, the median CD4 count was 237 cells/mm³ (IQR: 85–397) and 28 of the 40 who were on antiretroviral therapy had an undetectable viral load. The characteristics of these patients are shown in Table 1. The most frequent histological type of LC was adenocarcinoma (24 cases; 39.3%), followed by squamous cell carcinoma (23 cases; 37.7%). The diagnosis in 80% of the patients was made in advanced stages of the disease (III and IV) and the treatment given was just palliative therapy (24 cases; 39.3%), chemotherapy (14 cases; 22.9%), surgery and chemotherapy (eight cases; 13.1%), radiotherapy (seven cases; 11.4%), surgery (four cases; 6.5%) and other combined measures (two cases; 3.2%). The median survival was three months and the likelihood of survival (Kaplan–Meier) at six and 12 months was 42% and 28.5% (Figure 1). There were no differences in the form of presentation or evolution between the patients with a detectable viral load and those with an undetectable viral load (data not shown). Table 2 shows some of the characteristics of the 61 HIV-infected patients with LC compared with 90 patients with LC (80% men) from the same geographical area and during the same period but with no evidence of HIV infection. The main differences found were that the group without HIV infection was older at diagnosis, contained fewer active smokers though with a greater pack year consumption, greater frequency of the squamous cell carcinoma histological subtype and fewer cases of adenocarcinoma. The presentation in advanced stages (groups III and IV) was similar in both groups.

Table 1.

Epidemiological and clinical characteristics of the HIV-infected patients with lung cancer (n = 61).

Gender
Male	50
Female	11
Mean age (years)	47.9 (41.7–52.9)
HIV transmission risk behaviour
Intravenous drug use	35 (57.3)
Homosexual contact	12 (19.6)
Heterosexual contact	10 (16.3)
Other	4 (6.5)
Time from HIV diagnosis (months)	125.6 (23.9–213.5)
Prior pulmonary events	29 (47.5)
Tuberculosis	16
Bacterial pneumonia	9
P. jiroveci pneumonia	4
CD4 count nadir (cells/mm³)	149 (42–232)
CD4 count at time of LC diagnosis	237 (85–397)
CD4 ≤350/mm³ at time of LC diagnosis	39 (63.5)
AIDS cases	34 (55.7)
On ART at time of LC diagnosis	40 (65.5)
Time on ART (months)	99.9 (23.7–151.4)
HIV viral load <50 copies/mL at time of LC diagnosis*	28 (70)
Palliative therapy	23
Median survival (months)	3.05 (1.2–8.8)
Died	46 (75.4)

Of the patients on ART.

The quantitative variables are expressed as median and IQR and the qualitative variables as n (%).

ART: antiretroviral therapy.

Figure 1.

Actuarial survival of the 61 patients with lung cancer and HIV infection.

Table 2.

Contrast between HIV-infected patients with LC (n = 61) and patients with LC but no evidence of HIV infection (n = 90).

HIV (n = 61)	No HIV (n = 90)	p
Male	50 (82)	75 (83)	ns
Age (years)	47.9 (41.7–52.9)	65.7 (58.5–71.8)	p < 0,0001
Active smokers (%)	59 (96.7)	52 (57.7)	p < 0.0001
Packs per year	35	65	p < 0.0001
Histology
Squamous cell carcinoma	24 (39.3)	53 (58.8)	p < 0.001
Adenocarcinoma	23 (37.7)	12 (13.3)	p < 0.002
Other	14 (23)	25 (27.8)
Stage (III and IV)	49 (80)	80 (88)	p < 0.6

The quantitative variables are expressed as median and IQR and the qualitative variables as n (%).

Of the 4721 HIV-infected patients, only 17% were women.

Discussion

LC is the most common non-AIDS-associated tumour in HIV-infected patients, in whom it has a higher frequency than in the general population.^4–12 The risk of LC among HIV-infected individuals is more pronounced in most previous studies, with adjusted incidence rate ratios ranging from 2.2 to 4.7 when comparing HIV-infected with uninfected persons.^{5,7–11,14–17} However, a recent study that compared HIV-infected and uninfected individuals enrolled in Kaiser Permanente observed demographically-adjusted incidence rate ratios of 1.8 and 1.2 in an adjusted analysis, including smoking.¹⁸ Although LC remains more common in men, in our series there was a notable presence of women. In our HIV-infected cohort, only 17% were women and the rate ratio of LC between the sexes was 1:1. A few previous studies have also found similar rates of LC in HIV-infected men and women.^19,20 Likewise, the relatively young age at LC diagnosis largely reflects the young age distribution of the HIV population,²⁰ although it could also reflect that development of the disease is earlier in HIV-infected patients than non-infected persons.^11,21 On the other hand, smoking, associated with the LC, was less common in the HIV-infected patients than the non-infected patients. This suggests that other factors apart from sex, age and smoking may influence the development of LC in this particular population. Over half the patients had already developed an AIDS-defining condition and large proportions had a low CD4 cell count at nadir and at diagnosis of the LC. This suggests that the immunosuppression plays a role in the development of LC.^17,18 Over half the patients had a history of some opportunistic lung disease. The role of inflammatory pulmonary disease and infections in the development of LC has long been known²², and this has also been seen in HIV-infected patients, particularly in association with recurrent pneumonias.^23,24 In almost all the series of LC in HIV-infected patients, the most usual histological type is adenocarcinoma.^11,15,16 In our series, the most common histological types were adenocarcinoma and squamous cell carcinoma, which accounted for almost the same number of cases, unlike in the general population where adenocarcinoma only accounts for 13% of cases. LC in both HIV-infected and uninfected populations presents at advanced stages, with a very high mortality in the HIV-infected population and no differences according to whether the viral load is or is not detectable. Previous studies including patients from the pre-highly active antiretroviral therapy (HAART) era suggested that HIV-infected patients with LC fare worse when compared with uninfected subjects; however, most recent studies note no significant difference in clinical outcome between patients with HIV and uninfected controls with LC.²⁵ In our study, the presentation in advanced stages (groups III and IV) was similar in both groups, which could be explained by the high percentage of patients on HAART, and most of them with undetectable HIV viral loads. We do not have data about survival of uninfected subjects.

In summary, LC is a common tumour in HIV-infected patients. It affects men and women equally, with a history of smoking and often a prior opportunistic lung disease. Affected patients are often immunosuppressed and have AIDS. Programmes are needed to encourage these patients to cease smoking, start antiretroviral therapy soon to prevent immunosuppression, and possibly consider screening for LC in the high-risk population.²⁶

Footnotes

Conflict of interest

The authors declare no conflict of interest.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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