A correlative analysis of PD-L1, PD-1, PD-L2, EGFR, HER2, and HER3 expression in oropharyngeal squamous cell carcinoma

We explored potential associations of the PD-1/PD-L1/PD-L2 pathway with clinical characteristics, outcome, and expression of EGFR, HER2, HER3 in oropharyngeal squamous cell carcinoma (OPSCC) using an institutional database. Protein expression was assessed by immunohistochemistry on tissue microarray sections (EGFR, HER2, HER3) or whole tissue sections (PD-1/PD-L1/PD-L2). Expression of EGFR, HER2, HER3, PD-L1, and PD-L2 was quantified on tumor cells. Maximum density of PD-1 positive lymphocytes was measured on a scale of 0-4 within the tumor mass and peritumoral stroma. Associations between biomarkers and patient outcomes were tested using descriptive and inferential statistics, logistic regression, and Cox proportional hazards models. We analyzed tissue samples from 97 OPSCC cases: median age 59 years, p16+ (71%), male (83.5%), never smokers (18%), stage 3-4 disease (77%). 25% of cases were PD-L1 positive. The proportion of PD-L1+ tumors was higher in p16+ (29%) than p16- OPSCC (11%, p=0.047). There was no correlation between PD-L1, PD-L2, PD-1, EGFR, HER2, or HER3 expression. Positive PD-L1 status correlated with advanced nodal disease on multivariate analysis (OR 5.53 (CI 1.06-28.77), p=0.042). Negative PD-L2 expression was associated with worse survival (HR 3.99 (1.37-11.58), p=0.011) in p16- OPSCC. Lower density of PD-1+ lymphocytes in peritumoral stroma was associated with significantly increased risk of death on multivariate analysis (HR=3.17 (CI 1.03-9.78), p=0.045) after controlling for prognostic factors such as stage and p16 status. PD-L1 expression on tumor cells correlates with p16 status and advanced nodal status in OPSCC. PD-1+ lymphocytes in peritumoral stroma serve as an independent prognostic factor for overall survival.

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