Soft palatal melanosis can be detected by visual inspection during routine physical examination or even personally in a mirror. The aim of this study was to evaluate the association between squamous cell neoplasia in the upper aerodigestive tract (UAT) and soft palatal melanosis. We reviewed digitized records of high-quality endoscopic images of the soft palate of 1786 Japanese alcoholic men who underwent endoscopic screening. Soft palatal melanosis was observed in 381 (21.3%) of the subjects (distinct, 6.3%). Older age, an inactive heterozygous aldehyde dehydrogenase-2 genotype, smoking, and a high mean corpuscular volume were positively associated with the presence of soft palatal melanosis. The age-adjusted odds ratio (95% confidence interval) for UAT neoplasia was 1.92 (1.40–2.64) in the group with melanosis and 2.51 (1.55–4.06) in the group with distinct melanosis, compared with the melanosis-free group. A multivariate analysis showed that the presence of soft palatal melanosis was independently associated with a high risk of UAT neoplasia. We calculated the individual number of risk factors out of four easily identifiable and significant factors: age ≥55 years, current/former alcohol flushing, mean corpuscular volume ≥106 fL, and distinct soft palatal melanosis. Compared with the risk-factor-free condition, the odds ratio (95% confidence interval) values of UAT neoplasia for one, two, three, and four risk factors were 1.49 (0.97–2.30), 3.14 (2.02–4.88), 4.80 (2.71–8.51), and 7.80 (2.17–28.1), respectively. The presence of soft palatal melanosis provides a simple new strategy for identifying heavy drinkers with a high risk for UAT neoplasia.
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