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

Abstract

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.