Objective Expression of the protein marker p 16INK4a is used as a surrogate for human papillomavirus (HPV) infection in biopsies of oral and tonsillar mucosa. While HPV infection accounts for Findings Fifteen of the 24 HGDs (62.5%), fourteen of the 24 LGDs (58.3%) and four of the 24 CMs (16.6%) were positive for p 16INK4a expression. The difference in p16 expression between HGD versus CM and LGD versus CM were analyzed by Wilcoxon signed rank test and statistically significantly different at level with p-values of 0.0001 and 0.0009, respectively. Greater p16 expression was noted in HGDs compared to LGDs (p-value = 0.01960, which was significant at level). A step-down Holm-Bonferroni method to account for multiple comparisons showed adjusted p-values of 0.0003 (HG versus CM), 0.0018 (LG versus CM) and 0.0196 (HG versus low LG) among three groups. Conclusion p16 expression was statistically-significantly greater in LGD and HGD lesions compared to CM, with a trend of greater expression being associated with higher grade of dysplasia.