Nevertheless, the presence of p16 throughout the epithelial transformations from mild to severe dysplasia suggests that viral infection is an important and independent event necessary for malignant transformation.40 The p16 IHC analysis is technically simple and appears to be a reliable indicator of HPV-associated high-grade oral squamous dysplasia.36 However, no definitive conclusion may be drawn from our findings on the causal relationship between p16 immunopositivity and the development of dysplasia. This evidence concerns the gene CDKN2A and dysplasia.