- HIV infection is
independently associated with an increased risk of lung cancer.
- With the advent
of anti-retroviral therapy (ART), and improved survival rates, there has
been an increase in the proportion of deaths occurring due to non-AIDS
defining solid tumors, especially lung cancer.
- Very little data
currently available to predict relationship between longitudinal
measurements of immune function and lung cancer risk in the setting of HIV
longitudinal cohort study assessed the risk of lung cancer development in
HIV patients in relation to their immune function and presence of chronic
Presence of impaired
immune response and chronic inflammation in the background of HIV infection
might contribute to an increased risk of lung cancer according to a recent
longitudinal cohort study conducted in the US.
Aim of the Study
wished to assess whether presence of impaired or dysfunctional immunity and
chronic lung infection and inflammation could contribute to an increased risk
of development of lung cancer in the background of HIV
. Currently not many studies
have been conducted in this regard.
‘High risk groups within the setting of HIV infection such as those with poor immune status and having chronic inflammation should be targeted for lung cancer preventive measures.’
Details of the
Participants for the
study were chosen from the amongst the Veterans Aging Cohort Study.
should have had HIV infection for a minimum of three years. This longitudinal
cohort study spanned from 1998 to 2012. The Cancer Registry was used to
identify incidental cases of lung cancer.
with HIV infection less than three years, and
also those with
a prevalent diagnosis of lung cancer and incomplete clinical and lab data were
regression models were employed to assess the relationship between (CD4 cell
count, CD8 cell count, CD4/CD8 ratio, HIV RNA, and bacterial pneumonia) and risk
of lung cancer.
model adjustments were made for smoking, age, race or ethnicity, hepatitis C
infection, history of chronic obstructive pulmonary disease and occupational
lung disease, and alcohol and drug use.
Findings of the Study
results of the study revealed the following -
Conclusions and Takeaway
from the Study
- 277 incidental lung cancer cases
were identified from amongst 21666 participants.
- An increased incidence of lung
cancer was associated with a decreased
CD4 cell count (p trend=0·001), low
CD4/CD8 ratio (p trend=0·0001), more
HIV RNA concentration (p=0·004), and higher number of cumulative bacterial pneumonia episodes (12
month lag only; p trend=0·0004), in distinct models for each time-updated
12 month lagged, 24 month simple moving average cumulative exposure,
- CD4/CD8 ratio and cumulative
bacterial pneumonia episodes were found to be statistically significant (p
trends 0·003 and 0·004, respectively), when including these parameters in
a mutually adjusted model.
study found evidence that dysfunctional
immune system activation and chronic inflammation could cause an increased
incidence of lung cancer
in the background of HIV infection.
findings of the study may be employed to target
lung-cancer preventive measures among high-risk
How HIV Infection May
Increase Lung Cancer Risk
remains a major risk factor among HIV
infected individuals for the development of lung cancer, since most of them are
heavy smokers and intravenous (IV) drug users.
studies conducted have found that HIV infection independently showed a
statistically significant risk for the development of lung cancer after
adjustments for individual smoking exposure were made. The following are
postulated as the possible mechanisms that operate in persons with HIV
infection to increase lung cancer risk
- Oncogenic potential of the HIV
- Immunosuppression and decreased immunosurveillance
related to HIV infection, akin to other AIDS defining cancers
- Recurrent lung infections and asthma
lead to a chronic inflammatory state, and predisposing to lung cancer
- HIV infection mediated genomic
instability, leading to an increased susceptibility to tobacco
evidence to support these potential mechanisms remains scarce.
Immune Activation in HIV Infection
immune system activation has been known to occur in HIV infection. Such unregulated
activation leads to a state of immunosuppression by decreasing CD4 cell counts,
direct inhibition of B cells and damage and destruction of the architecture of
tissues essential for T cell function and homeostasis such as lymph node,
thymus and bone marrow. Additionally, such uncontrolled activation of the
immune system causes its premature aging and senescence.
immune activation has been shown to be associated with elevated levels of
inflammatory and coagulopathy markers such as hs-C-reactive protein, IL-6 and
immunosuppression and chronic inflammatory state induced by chronic immune
activation might probably play a role in enhancing the risk of development of
Scope of Future Research
in This Area
is necessary for further studies to be conducted to better understand the
mechanisms such as immune dysfunction and their role in the development of lung
cancer in HIV infected persons. This
might lead to development of novel treatment modalities and tools to minimize
lung cancer risk in this population.
research employing biological markers for pulmonary infections and
inflammation, is necessary to understand how lung infection and
inflammation operate in HIV infected persons to increase lung cancer risk.
- HIV Infection Is Associated with an Increased Risk for Lung Cancer, Independent of Smoking - (http://cid.oxfordjournals.org/content/45/1/103.ful)
- Epidemic of Lung Cancer in Patients With HIV Infection - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3619638)
- Pulmonary infections and risk of lung cancer among persons with AIDS - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955766)
- Factsheet Lung cancer - (http://www.aidsmap.com/Lung-cancer/page/1044696)
- Biomarkers of immune dysfunction in HIV - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3032605/)
- HIV-associated chronic immune activation - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3729961/)