Analysis of p16^INK4A expression of oral squamous cell carcinomas in Taiwan: Prognostic correlation without relevance to betel quid consumption

Objectives: In this study, we examined the role of p16^INK4A, a surrogate biomarker of HPV-related head and neck cancers with better prognosis, in an endemic area of betel quid (BQ)-related oral squamous cell carcinoma (OSCC). Methods: p16^INK4A immunohistochemistry was examined in 165 OSCCs, statistical analyses were performed to elucidate the correlation between p16^INK4A expression and BQ habits/pathologic features, and the prognostic impact of p16^INK4A and different parameters were analyzed. Results: The incidence of p16^INK4A expression was similar between BQ chewers and non-chewers. p16^INK4A expression was significantly associated with nodal metastasis (P = 0.005). There was a trend suggesting that the loss of p16^INK4A expression was more frequent in higher T stages, however, this was found only in patients without lymph node metastasis (P = 0.059). A poorer prognosis and a higher risk of tumor recurrence were found in OSCCs without p16^INK4A expression. (The HR for cancer-specific mortality and cancer recurrence was 3.55 and 1.89, respectively.) Conclusion: Although it has been suggested that BQ chewers had a greater tendency toward tumor recurrence and poor outcome, our data demonstrated that p16 ^INK4A expression is unrelated to BQ habit and that p16 ^INK4A downregulation is a strong predictor for OSCC progression, recurrence and survival in Taiwan.