Utility of p53 Immunohistochemistry in Diagnosis of Human Papillomavirus Associated Oral Epithelial Dysplasia: A Retrospective Study of 105 Patients

Abstract

Introduction

Evaluation of p53 immunohistochemistry (IHC) in oral epithelial dysplasia (OED) has demonstrated a characteristic staining pattern in cases associated with high-risk human papillomavirus (HPV), identical to the pattern of expression reported in HPV associated dysplasia of the vulva. The accuracy of p53, in combination with p16, as a surrogate marker for HR HPV infection in OED, has not been extensively studied.

Materials & Methods

Expression of p53 was evaluated in 105 cases of HR HPV positive oral cavity OED, in which 104 cases were p16 positive and 1 case was p16 negative. HPV status was confirmed by RT-qPCR for E6 mRNA or RNA in situ hybridization (ISH). 7 cases of p16 positive oral cavity OED with abnormal p53 expression and/or TP53 mutation had negative HPV RNA ISH and were excluded.

Results

Our cohort included 96 males and 9 females, with a median age of 57 years (range 32-89). 93% of cases demonstrated classic HPV-associated basaloid morphology, and 7% of cases were keratinizing. The floor of mouth/ventral tongue were the most affected sites (61%), followed by the lateral tongue (18%) and gingiva (13%). 76% of cases demonstrated null-like/basal sparing pattern with p53 staining and 24% demonstrated a mid-epithelial/basal sparing pattern. 11 cases had an associated squamous cell carcinoma at the time of initial biopsy. A single case progressed to squamous cell carcinoma in an immunosuppressed patient, and 16 cases recurred. Of the cases with recurrence, 38% recurred more than once.

Conclusions

This study unequivocally demonstrates that p53 IHC, in combination with p16, can accurately identify HPV OED. Further, p53 can correctly identify p16 positive HR HPV negative p53 mutant OED with basaloid morphology. HPV OED can present with invasive SCC, but malignant progression in HPV OED is extremely rare.