Human papillomavirus (HPV) can establish productive infection in dysplastic oral mucosa, but HPV status is poorly predicted by histological features and p16 expression.

This study demonstrates, for the first time, that a minority of severely dysplastic oral lesions harbour productive, biologically relevant HPV infection. Consideration should be given to the specific assessment of HPV status in severe epithelial dysplasia cases, as both p16 status and the presence of karyorrhectic cells are poor predictive markers of HPV status.