Clinicopathologic Aspects of Vocal Fold Leukoplakia in Smokers and Nonsmokers

We aimed to investigate possible causes of leukoplakia and squamous cell carcinoma. We particularly sought to characterize the effect of smoking history because leukoplakia has been observed in nonsmokers.

We retrospectively identified patients with a diagnosis of leukoplakia who were treated at Mayo Clinic (Jacksonville, Florida), in the Department of Otorhinolaryngology, from 1/1/2006 through 8/31/2019. Each patient was age- and sex-matched (1:2 ratio) to control patients without leukoplakia. Information about possible risk factors, chief symptoms, and social history with smoking and alcohol use was obtained from health records. Nine risk factors were analyzed independently with multivariate analysis. Continuous risk factors were compared between cases and controls with the Wilcoxon rank sum test; categorical variables were compared with the χ² test.

The final cohort consisted of 72 patients with leukoplakia (mean [SD] age, 66 [11] years; 61 men [85%]) and 144 age- and sex-matched controls. Compared with the control group, significantly more cases were current smokers (26% vs. 5%) and fewer were never-smokers. (17% vs. 51%) (P < 0.001). Cases also had a significantly longer duration of smoking history compared with controls (median, 30 vs. 0 years; P < 0.001). Alcohol consumption was not significantly different between cases and controls (53% vs. 54%; P > 0.99). When assessing never-smokers and those who had not smoked for more than 25 years, a history of smoking (P = 0.002) and the number of years smoked (P = 0.002) were significantly different for cases and controls.

Most vocal fold leukoplakia lesions have a low risk of malignancy. It is important to evaluate the characteristics of the lesion and assess the patient's risk factors. Follow-up is a key factor in patient management, but for patients with recurrent leukoplakia, the duration and frequency of surveillance is still controversial and varies among medical centers. Future prospective studies with advanced analyses are warranted because they may strengthen the ability to identify clinical factors that influence the development of squamous cell carcinoma.