Alcohol Consumption and Multiple Dysplastic Lesions Increase Risk of Squamous Cell Carcinoma in the Esophagus, Head, and Neck

Chikatoshi Katada, Tetsuji Yokoyama, Tomonori Yano, Kazuhiro Kaneko, Ichiro Oda, Yuichi Shimizu, Hisashi Doyama, Tomoyuki Koike, Kohei Takizawa, Motohiro Hirao, Hiroyuki Okada, Takako Yoshii, Kazuo Konishi, Takenori Yamanouchi, Takashi Tsuda, Tai Omori, Nozomu Kobayashi, Tadakazu Shimoda, Atsushi Ochiai, Yusuke Amanuma, Shinya Ohashi, Tomonari Matsuda, Hideki Ishikawa, Akira Yokoyama, Manabu Muto

Some patients develop multiple squamous cell carcinomas (SCCs) in the upper aero-digestive tract, attributed to field cancerization; alcohol consumption has been associated with this process. We examined the association between multiple areas of dysplastic squamous epithelium with development of SCC of the esophagus or head and neck cancer, as well as alcohol consumption and smoking. We examined 331 patients with early-stage esophageal SCC using lugol chromoendoscopy to evaluate the dysplastic squamous epithelium in the esophagus. Patients were then assigned to 3 groups, based on number of lugol-voiding lesions (LVL): A=no lesion, B=1-9 lesions, C=10 or more lesions. Participants completed lifestyle surveys on histories of drinking, smoking, and diet. All participants were evaluated by laryngo-pharyngoscopy before registration; only those without head and neck cancer were included, except for patients with superficial SCC limited to the subepithelial layer. Lesions detected in the esophagus and head and neck by surveillance were considered to be metachronous. The study endpoint was the cumulative incidence of metachronous SCCs in the esophagus and head and neck after endoscopic resection of esophageal SCC, according to the grade of LVL. At study entry, all patients were instructed to abstain from alcohol and smoking. Over the 2 year study period, metachronous SCCs of the esophagus were detected in 4% of patients in group A, 9.4% of patients in group B, and 24.7% of patients in group C (P<.0001 for patients in group A vs B or B vs C). Head and neck SCCs were detected in none of the patients in group A, 1.7% of the patients in group B, and 8.6% of the patients in group C (P=.016 for patients in group A vs C and P=.008 for patients in group B vs C). SCC of the esophagus or head and neck developed in 4.0% of patients in group A, 10.0% of patients in group B, and 31.4% of patients in group C (P<.0001 for group A vs group B or group A vs C). Alcohol abstinence decreased the risk of multiple SCC of the esophagus (adjusted hazard ratio, 0.47, 95% CI, 0.25-0.91; P=.025), whereas smoking abstinence did not. Multiple dysplastic lesions in the esophagus increase risk of multiple SCCs. Alcohol abstinence reduces risk of metachronous SCC. Clinical Trials Registry ID no: UMIN000001676 and UMIN000005466.