Risk of Oral Nonmalignant Lesions Associated With Human Papillomavirus Infection, Betel Quid Chewing, and Cigarette Smoking in Taiwan: An Integrated Molecular and Epidemiologic Study

Abstract

Abstract Context.—In contrast to previous studies about the association of oral squamous cell carcinoma with human papillomavirus (HPV) 16/18, the associations between nonmalignant oral lesions (chronic inflammation, submucous fibrosis, leukoplakia, and squamous papilloma) and HPV are much less well understood. Objective.—We conducted this study using an in situ polymerase chain reaction in situ hybridization assay, which is one of the most sensitive methods for in situ viral detection. Other known oral cancer risk factors, including betel quid chewing and cigarette smoking, were also analyzed. Design.—Oral specimens from 23 patients with submucous fibrosis, 36 patients with leukoplakia, 22 patients with squamous papilloma, and 21 patients without significant lesions were analyzed for the presence of HPV DNA. Their betel quid chewing and cigarette smoking histories were reviewed. Results.—HPV-16 and HPV-18 were frequently identified in all 3 oral lesions (61.5% and 42.1%), while HPV-6 and HPV-11 were seen only in squamous papilloma (21.1% and 5.0%). HPV-18, betel quid chewing, and smoking were significantly associated with leukoplakia and squamous papilloma, while only betel quid chewing and smoking were significantly associated with submucous fibrosis. Multivariate analysis showed that the betel quid chewing habit remained an independent factor for leukoplakia and squamous papilloma. Conclusions.—Our data indicated that betel quid chewing and smoking habits are 2 important risk factors for these nonmalignant or premalignant oral lesions, while for high-risk HPV, only HPV-18—not HPV-16—is a significant risk factor for leukoplakia and squamous papilloma.