Role of the human papillomavirus in malignant transformation of oral leukoplakia distinct from oropharyngeal squamous cell carcinoma: A study of 76 patients with internal-control specimens

Abstract

This study sought to investigate the role of human papillomavirus (HPV) in the carcinogenesis of oral leukoplakia (OLK), with the oral cavity as the site of interest. A total of 76 patients (152 specimens) were enrolled in the study. The patients were divided into 2 groups: the malignant transformation of OLK (OLK-MT) group and the non-malignant transformation of OLK (OLK-non-MT) group. HPV reverse dot blot analysis, HPV DNA polymerase chain reaction (PCR), and p16INK4A immunohistochemistry (IHC) were used to determine HPV infection status. Transformation of OLK commonly occurred in the lateral/ventral tongue, buccal mucosa, and gingiva. On the basis of the initial analysis of specimens, only 5.3% (4 of 76) of patients were found to be HPV-16 positive, and these patients' final specimens yielded negative results. Overexpression of p16INK4A in the dysplastic stage was associated with the transformation of OLK (P = .013; odds ratio = 3.544). Transformation of OLK was common in patients who are elderly, in females, and in nonsmokers/nondrinkers; lesions were located in the lateral/ventral tongue, with dysplasia and overexpressed p16INK4A seen during the initial stage. HPV may be an opportunistic infection in the oral cavity and may not be a cause of malignant transformation of OLK. p16INK4A expression, which initially increases and then diminishes or disappears, may be an early predictor of malignant transformation.