Prognosis of HPV-positive squamous cell carcinoma of tonsil-expressing high level of p16 and low level of EGFR.

Abstract

5546 Background: HPV infection has been known to be one of the important risk factors for carcinogenesis of head and neck squamous cell carcinoma (HNSCC). The over-expression of epidermal growth factor receptor (EGFR) correlates with a poor prognosis in HNSCC. We investigated the relationship between HPV status and EGFR expression and the prognostic impact of these markers in tonsil cancer. Methods: Eligibility criteria was the patients diagnosed as SCC of tonsil and received curative radical resection with available tumor tissue samples. In situ hybridization for HPV and immunohistochemistry for p16, EGFR, and p53 were performed. Results: Among 66 tonsil cancer patients, 24 (36.3%) patients showed HPV positivity. There were no statistically significant differences in clinical characteristics including sex, age, smoking history, TNM stage and treatment modalities between HPV-positive and -negative patients. The over-expression and high intensity of p16 had significant correlation with HPV positivity (p=0.003, 0.017). However, no correlation was found between p53 and HPV infection. There was a trend that the proportion of EGFR over-expression was greater in HPV-negative than in HPV-positive patients (p=0.082), and no or low EGFR intensity was observed in the patients showing p16 over-expression (p=0.015). Among the HPV-positive patients, the frequency of EGFR over-expression was significantly higher in ex- or current smokers (p=0.005). There was meaningful difference of three years disease-free survival between never smokers showing both over-expression of p16 and low expression of EGFR and the others (90.0% and 73.5%, respectively, p=0.082). On univariate analysis, the significant clinicopathologic factors affecting disease-free survival were smoking history and EGFR intensity (p=0.020 and 0.017, respectively). Conclusions: Taken together, p16 was a good surrogate marker for HPV infection. The expression of EGFR was inversely correlated with HPV positivity, but HPV-positive patients with smoking history showed EGFR over-expression. In the HPV-positive tonsil cancers, high p16 and low EGFR expression should be considered as favorable prognostic markers. No significant financial relationships to disclose.