Correlation of immune makers with HPV 16 infections and the prognosis in oropharyngeal squamous cell carcinoma

免疫标志物与HPV 16感染及口咽鳞状细胞癌预后的相关性

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Abstract

OBJECTIVES: This study aims to investigate the association of immune markers with high risk human papillomavirus 16 (HPV 16) infection status and to evaluate the prognostic value of programmed death ligand-1 (PD-L1) in patients with oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: This retrospective study collected 50 cases of HPV positive and HPV negative OPSCC from January 2011 to December 2015. The correlation of CD8 + tumor infiltrating lymphocytes (TILs), programmed death-1 (PD-1), and PD-L1 expression with HPV 16 infection status was analyzed via immunofluorescent staining and quantitative real-time PCR. RESULTS: There was no significant difference in the baseline data between the two groups. Patients with HPV + OPSCC had better prognosis compared to HPV - patients (5-year overall survival [OS], 66% vs. 40%, P = 0.003; 5-year disease specific survival [DSS], 73% vs. 44%, P = 0.001). The expressions of immunity related makers were significantly higher in the HPV + group than the HPV - group (CD8 + TIL: P = 0.039; PD-L1: P = 0.005; PD-1: P = 0.044). Positive CD8 + TIL and PD-L1 were independent factors for better prognosis of OPSCC (DSS, P < 0.001; OS, P < 0.001, respectively). Kaplan-Meier survival analysis indicated that patients with TILs of high HPV + /CD8 + expression were more likely to have better prognosis than those with TILs of low HPV + /CD8 + expression (DSS, P < 0.001; OS, P < 0.001), TILs of high expression of HPV - /CD8 + (DSS, P = 0.010; OS, P = 0.032), and TILs of low expression of HPV - /CD8 + (DSS, P < 0.001; OS, P < 0.001). Furthermore, HPV + /PD-L1 + OPSCC patients had significant better prognosis compared to patients with HPV + /PD-L1 - (DSS, P < 0.001; OS, P = 0.004), HPV - /PD-L1 + (DSS, P = 0.010; OS, P = 0.048) and HPV - /PD-L1 - (DSS, P < 0.001; OS, P < 0.001). CONCLUSIONS: HPV + OPSCC had a significantly better prognosis, and PD-L1 expression was elevated in HPV + OPSCC. PD-L1 positivity might be related to the better prognosis of HPV + OPSCC. CLINICAL RELEVANCE: This study provides a theoretical basis and baseline data for the application of immune checkpoint inhibitors in head and neck tumors.

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