Tobacco Addiction and The Risk of Upper Aerodigestive Tract Cancer in A Multicenter Case-Control Study

Background: While previous studies on tobacco and alcohol and the risk of upper aerodigestive tract (UADT) cancers have clearly shown dose-response relations with the frequency and duration of tobacco and/or alcohol, studies on addiction to tobacco itself as a risk factor for UADT cancer have not been published, to our knowledge. The aim of this report is to assess whether smoking addiction is a risk factor for UADT SCC risk in the multicenter case-control study (ARCAGE) in Western Europe independent of tobacco smoking or alcohol drinking intensity or duration.

Methods: The analyses included 1,905 ever smoking UADT SCC cases (871 oral cavity/oropharynx, 814 hypopharynx/larynx, 127 esophagus, and 93 overlapping oral cavity/pharynx) and 1,489 ever smoking controls. The addiction variables included first cigarette after waking up, difficulty refraining from smoking in places where it is forbidden, and cigarettes per day. Odds ratios (OR) and 95% confidence intervals (95% CI) for UADT cancers with addiction variables were estimated with unconditional logistic regression, adjusting for center, age, sex, education level, alcohol consumption, and tobacco smoking.

Results: Among current smokers, 76.47% of cases were categorized in the highest addiction level, whereas 54.69% of controls were in that category. The participants who smoked their first cigarette within 5 minutes of waking up were two times more likely to develop UADT SCC (OR = 2.22, 95% CI 1.57–3.15) than those who smoked 60 minutes after waking up. A higher modified Fagerstram score, reflecting greater tobacco addiction, was associated with an increased risk of UADT SCC among current smokers, but not among former smokers.

Conclusion: We observed that time to first cigarette after waking up was associated with UADT SCC risk, regardless of heavy smoking or alcohol drinking behaviors. These results are consistent with residual effect of smoking that was not captured by the questionnaire responses alone.