Utility of p53 and p16 immunohistochemistry in the diagnosis of human papillomavirus‐associated oral epithelial dysplasia: a retrospective study of 105 patients

Aims This study investigated the utility of combined p16 and p53 immunohistochemistry (IHC) for diagnosing high‐risk human papillomavirus (HR HPV)‐associated oral epithelial dysplasia (OED) and its associated clinical behaviour, including disease recurrence and transformation to malignancy. Methods and Results The expression of p53 was evaluated in 105 cases of HR HPV‐positive oral cavity OED, of which 104 were scored as positive for p16. HPV status was confirmed by reverse transcriptase quantitative polymerase chain reaction (RT‐qPCR) for E6 mRNA or RNA in situ hybridization (ISH). Seven cases of p16‐positive oral cavity OED with abnormal p53 expression and/or TP53 mutation and negative HPV RNA ISH were excluded. Most cases (93%) demonstrated classic HPV‐associated basaloid morphology, and 7% were keratinizing. The most affected sites were the floor of the mouth/ventral tongue (61%), followed by the lateral tongue (18%) and gingiva (13%). p53 IHC showed that 76% of cases demonstrated a null‐like / basal‐sparing pattern, while 24% demonstrated a mid‐epithelial/basal sparing pattern. Ten cases exhibited an invasive or suspicious for microinvasive component on biopsy. Dysplasia recurred in 14 cases, and a single case transformed to squamous cell carcinoma. Conclusion The combination of p16 positivity and a basal‐sparing pattern of p53 is predictive of HR HPV in OED, eliminating the need for further HPV‐specific testing. Although HPV OED may co‐occur with invasive squamous cell carcinoma on biopsy, the transformation to malignancy is low.