Association between PD-L1 and HPV Status and the Prognostic Value of PD-L1 in Oropharyngeal Squamous Cell Carcinoma
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Purpose Oropharyngeal squamous cell carcinoma (OSCC) has been recognized as an immunosuppressive disease. Various mechanisms have been proposed for immune escape, including dysregulation of immune checkpoints such as the programmed cell death 1:programmed cell death-ligand 1 (PD-L1) pathway. We investigated the expression of PD-L1 in human papillomavirus (HPV)–negative and HPV-positive OSCC to determine its prevalence and prognostic relevance. Materials and Methods Using immunohistochemistry, 133 cases of OSCC were evaluated for expression of PD-L1. Formalin-fixed paraffin-embedded tumor samples were stained with monoclonal antibody (clone 5H1) to PD-L1. PD-L1 positivity was defined as membrane staining in ! 20% of tumor cells. Correlations between PD-L1 expression and HPV status and survival parameters were analyzed. Results Of the 133 patients, 68% showed PD-L1 expression, and 67% of patients were positive for p16 expression by immunohistochemistry. No significant difference in PD-L1 expression was observed between HPV(–) and HPV(+) tumors (61% vs. 71%, p=0.274). No significant difference in age, gender, smoking history, location of tumor origin, or stage was observed according to PD-L1 status. With a median follow-up period of 44 months, older age (! 65 years) (p=0.017) and T3-4 stage (p < 0.001) were associated with poor overall survival (OS), whereas PD-L1 expression did not affect OS in univariate and multivariate analysis. Conclusion PD-L1 expression was observed in the majority of OSCC patients regardless of HPV status. Further large prospective studies are required to determine the role of PD-L1 expression as a prognostic or predictive biomarker, and clinical studies of immune checkpoint inhibitors in OSCC are warranted regardless of HPV status.
Abstract
Purpose Oropharyngeal squamous cell carcinoma (OSCC) has been recognized as an immunosuppressive disease. Various mechanisms have been proposed for immune escape, including dysregulation of immune checkpoints such as the programmed cell death 1:programmed cell death-ligand 1 (PD-L1) pathway. We investigated the expression of PD-L1 in human papillomavirus (HPV)–negative and HPV-positive OSCC to determine its prevalence and prognostic relevance. Materials and Methods Using immunohistochemistry, 133 cases of OSCC were evaluated for expression of PD-L1. Formalin-fixed paraffin-embedded tumor samples were stained with monoclonal antibody (clone 5H1) to PD-L1. PD-L1 positivity was defined as membrane staining in ! 20% of tumor cells. Correlations between PD-L1 expression and HPV status and survival parameters were analyzed. Results Of the 133 patients, 68% showed PD-L1 expression, and 67% of patients were positive for p16 expression by immunohistochemistry. No significant difference in PD-L1 expression was observed between HPV(–) and HPV(+) tumors (61% vs. 71%, p=0.274). No significant difference in age, gender, smoking history, location of tumor origin, or stage was observed according to PD-L1 status. With a median follow-up period of 44 months, older age (! 65 years) (p=0.017) and T3-4 stage (p < 0.001) were associated with poor overall survival (OS), whereas PD-L1 expression did not affect OS in univariate and multivariate analysis. Conclusion PD-L1 expression was observed in the majority of OSCC patients regardless of HPV status. Further large prospective studies are required to determine the role of PD-L1 expression as a prognostic or predictive biomarker, and clinical studies of immune checkpoint inhibitors in OSCC are warranted regardless of HPV status.
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