1956 - Drinking alcohol, smoking, multiple dysplastic lesions and the risk of field cancerization of squamous cell carcinoma in the esophagus and head and neck region

Background

Multiple development of squamous cell carcinoma (SCC) in the upper aero-digestive tract is known as the field cancerization phenomenon. We examined the association of this phenomenon with dysplastic squamous epithelium in the background mucosa, drinking alcohol, and smoking.

Methods

331 patients with early esophageal SCC were enrolled. Using Lugol chromoendoscopy, we evaluated the dysplastic squamous epithelium in the esophagus. Lugol voiding lesions (LVL) were graded into 3 categories (A = no lesion; B = 1 to 9 lesions; C ≥ 10 lesions). The endpoint of this cohort study was the cumulative incidence of metachronous multiple SCC in the esophagus or 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 drinking alcohol and smoking. Data collected from a different cross-sectional cohort (n = 1042) were used as an historical control. ALDH2 status was determined by questionnaire facial flushing after drinking alcohol (present and past flushing=inactive ALDH2, never flushing=active ALDH2).

Results

In the median follow-up period of 69.6 months, LVL grade (A to B to C) was associated with progressive increases in the 5-year cumulative incidence of metachronous multiple SCC (esophagus = 6.0%, 17.8% and 47.1%, respectively, p = 0.022 for A vs. B and p < 0.0001 for A vs. C; head and neck = 0.0%, 4.3% and 13.3%, respectively, p = 0.12 for A vs. B and p = 0.0007 for A vs. C; esophagus or head and neck = 6.0%, 19.8% and 52.6%, respectively, p = 0.012 for A vs. B and p < 0.0001 for A vs. C). Alcohol and smoking abstinence decreased the risk of multiple SCC of the esophagus (adjusted hazard ratio=0.47 and 0.49, respectively) (p = 0.013 for alcohol and p = 0.024 for smoking). Adjusted odds ratio (OR) of LVL grade B and C associated with heavy drinking was significantly stronger in inactive ALDH2 (OR = 47.5 and 358, respectively) than active ALDH2 (OR = 12.8 and 138, respectively) (p < 0.05 for B and p < 0.05 for C).

Conclusions

Multiple dysplastic lesions in the esophagus are a useful predictor of the risk of multiple SCC associated with field cancerization. Alcohol and smoking abstinence is required to prevent a second primary SCC.

Clinical trial identification

UMIN000001676.

Editorial acknowledgement

Legal entity responsible for the study

JEC study group.

Funding

National Cancer Center Research and Development Fund 36 by the Ministry of Health, Labour and Welfare of Japan.

Disclosure

All authors have declared no conflicts of interest.