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Smoking, not Immune Deficiency is Major Cause of Lung Cancer for People with HIV

Lung cancer was strongly linked to smoking among participants in the Swiss HIV Cohort Study, but did not appear to be clearly associated with reduced CD4 cell levels, according to a report in the January 12, 2012, advance online edition of the British Journal of Cancer. Fortunately, another recent study showed that counseling by HIV care physicians can help patients stop smoking.

Several studies have showed that cancers caused by infectious pathogens -- such as human papillomavirus (HPV) for cervical and anal cancer, or hepatitis B and C for liver cancer -- are more common among HIV positive people compared with the general population, while rates of most non-infectious cancers are similar. Studies have produced conflicting findings regarding lung cancer, however.

Gary Clifford from the International Agency for Research on Cancer and fellow investigators with the Swiss HIV Cohort Study Group conducted an analysis of factors contributing to lung cancer among people with HIV.

The researchers identified 68 lung cancer cases among HIV positive people in the Swiss HIV Cohort or through linkage with Swiss Cancer Registries during 1985-2010. These case patients were matched to 337 HIV positive control patients without lung cancer by sex, age, HIV transmission category, and calendar period. Most (about 80%) were men and the average age at the time of lung cancer diagnosis was 50 years.

Results

•   96% of patients with lung cancer were current (85%) or former (6%) smokers, compared with 73% of control patients without lung cancer (about 50% current and about 25% former).
• Smoking had a strong association with lung cancer, with an odds ratio (OR) of 14.4 for current vs never smokers, or more than 14 times higher risk.
• Former smokers had a significantly reduced risk of lung cancer compared with current smokers (OR 0.22).
• No significant associations were seen between absolute CD4 T-cell count and lung cancer risk, either measured within 1 year before lung cancer diagnosis (OR 1.21 for < 200 vs 500 cells/mm³) or further back in time.
• Low CD4/CD8 ratio within 1 year before lung cancer diagnosis had a trend toward association with higher risk, but this did not reach statistical significance.
• Use of combination antiretroviral therapy (ART) was not significantly associated with lung cancer risk (OR 0.67 for ever vs never using ART).
• History of an AIDS diagnosis also was not significantly linked to increased lung cancer risk (OR 0.49), even among people with HIV-related pulmonary disease (OR 0.53).

Based on these findings, the researchers concluded, "Lung cancer in the Swiss HIV Cohort Study does not seem to be clearly associated with immunodeficiency or AIDS-related pulmonary disease, but seems to be attributable to heavy smoking."

Explaining why lung cancer appeared more common after the advent of effective combination ART, they noted that this reflects people with HIV staying alive long enough to develop the cancer.

Smoking Cessation

In a related study published in the January 18, 2012, advance online edition of HIV Medicine, researchers with the Swiss HIV Cohort Study looked at an intervention to reduce smoking among people with HIV.

The intervention, which was conducted only at the Zurich center, included a half-day standardized training for HIV physicians covering counseling of smokers, information about nicotine dependence and withdrawal, and smoking cessation medications.

Physicians received a checklist for semi-annual documentation of their counseling. Patients' smoking status was compared between participants at the Zurich center and other Swiss HIV Cohort Study institutions.

Results

• Overall, between April 2000 and December 2010, a total of 11,056 Swiss HIV Cohort Study participants had 121,238 semi-annual visits, reflecting 64,118 person-years of follow-up.
• During the intervention at the Zurich center between November 2007 and December 2009, a total of 1689 participants had 6068 visits.
• Physicians at the Zurich center reported that they included smoking cessation counseling during 80% of visits by smokers.
• The overall prevalence of smoking in the cohort decreased from 60% to 43% during the follow-up period.
• Patients at the Zurich center were significantly more likely to have stopped smoking than participants at other institutions, with an odds ratio (OR) of 1.23, or 23% increased likelihood of quitting (P = 0.004).
• Patients at the Zurich center were also less likely to relapse and resume smoking  (OR 0.75, or 25% less likely; P = 0.007).
• While some of the reduction in smoking was attributable to the passage of time -- as there was an overall trend toward quitting -- the effect of the intervention was stronger than the calendar effect (OR 1.19 vs 1.04 per year, respectively).
• People with prior cardiovascular events such as heart attacks were more likely to quit smoking.
• Middle-aged people, injection drug users, heavy alcohol drinkers, and individuals with depression or other psychiatric conditions were less likely to stop smoking.

Based on these finings, the study authors concluded, "An institution-wide training program for HIV care physicians in smoking cessation counseling led to increased smoking cessation and fewer relapses."

Investigator affiliations:

Clifford study: International Agency for Research on Cancer, Lyon, France; Epidemiology and Biostatistics Unit, Scientific Directorate, National Cancer Institute, Aviano, Italy; Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland; Cancer Registry of the Canton of Geneva, Switzerland; Cancer Registry of the Canton of Zurich, Switzerland; Cancer Registry of the Canton of Vaud, Lausanne, Switzerland; Cancer Registry of Basel, Switzerland; Cancer Registry of St Gallen and Appenzell, St Gallen, Switzerland; University Hospital, University of Bern, Switzerland; University Hospital Zurich, University of Zurich, Switzerland; Cantonal Hospital, St Gallen, Switzerland; University Hospital Basel, Switzerland; Ospedale Regionale, Lugano, Switzerland; University Hospital Lausanne, Switzerland; University Hospital Geneva, Switzerland; Coordination and Data Center, Swiss HIV Cohort Study, Lausanne, Switzerland.

Huber study: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland; Division of Biostatistics, Institute for Social and Preventive Medicine, University of Zurich, Switzerland; Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Switzerland; Division of Infectious Diseases, Berne University Hospital and University of Berne, Switzerland; Division of Infectious Diseases, University Hospital Basel, Switzerland; Division of Infectious Diseases, University Hospital Geneva, Switzerland; Division of Infectious Diseases, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland; Division of Infectious Diseases, Cantonal Hospital of St Gallen, Switzerland; Division of Infectious Diseases, Regional Hospital, Lugano, Switzerland.

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References

GM Clifford, M Lise, S Franchesi, et al (Swiss HIV Cohort Study Group). Lung cancer in the Swiss HIV Cohort Study: role of smoking, immunodeficiency and pulmonary infection. British Journal of Cancer. January 12, 2012 (Epub ahead of print).

M Huber, B Ledergerber, R Sauter, et al (Swiss HIV Cohort Study Group). Outcome of smoking cessation counselling of HIV-positive persons by HIV care physicians. HIV Medicine. January 18, 2012 (Epub ahead of print).