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BACKGROUND AND STUDY AIMS The prevalence of esophageal squamous-cell carcinoma in high-risk patients and the advantages of systematic Lugol staining during esophagoscopy have not yet been evaluated in a large prospective study. In this study we aimed to assess the prevalence of this type of tumor in high-risk patients, to examine the role of Lugol staining in endoscopic screening for esophageal squamous-cell carcinoma, and to establish whether it is possible to identify a particularly high-risk group which would benefit from systematic screening. PATIENTS AND METHODS A prospective study was undertaken in 62 endoscopy centers. A total of 1095 patients were enrolled, none of whom had any esophageal symptoms. These patients had presented with either a past history of or a recent head and neck or tracheobronchial squamous-cell carcinoma (group 1), with alcoholic chronic pancreatitis (group 2), with alcoholic cirrhosis (group 3), or were alcohol and tobacco addicts (group 4). The patients underwent a meticulous endoscopic examination of the esophagus, followed by Lugol staining. RESULTS The prevalence of esophageal squamous-cell carcinoma was 3.2 %. The group 1 patients showed the highest prevalence of carcinoma (5.3 %) and the highest prevalence of dysplasia (4.5 %). Of the 35 carcinomas detected in the 1095 patients, seven (20 %) were early lesions, and 20 % were only detected after Lugol staining (P = 0.02). High-grade dysplasia was only observed in group 1 patients and two-thirds of these lesions were only diagnosed after Lugol staining. The overall prevalence of low-grade dysplasia was 2.4 %, and 77 % of these were detected only after Lugol staining (P < 0.001). CONCLUSIONS Lugol dye staining increases the sensitivity of esophageal endoscopy for the detection of high-grade dysplasia and cancer. The prevalence of dysplasia and cancer reached 9.9 % in group 1, and we therefore believe that an endoscopic screening program could be justified for patients with head and neck or tracheobronchial cancer.