PD-L1 expression in malignancies contributes to an immunosuppressive microenvironment and disruption of anti-tumoral immune responses. Data are limited on the association between PD-L1 expression and survival in OSCC, overall and by HPV p16 status. We explored the prognostic effect of PD-L1 and p16 in localized or locally advanced OSCC treated with primary RT.
Patients (pts) diagnosed with OSCC from 2000-12 were identified from the Danish Head and Neck Cancer database (DAHANCA). PD-L1 expression was measured in tumor tissue using Agilent’s investigational PD-L1 imunohistochemistry (IHC) PharmDx Assay (clone 22C3). PDL1+ expression was defined as a score >1 using Tumor Proportion Score (TPS) as % of neoplastic cells expressing PDL1 at any intensity, Mononuclear Inflammatory Density Score (MIDS) as the estimate of PDL1 expressing mononuclear inflammatory cells associated with neoplastic cells, and Combined Positive Score (CPS) calculated using both TPS and MIDS. HPV oncogene expression was assessed using a > 70% cut-point for p16 IHC (clone E6H4). Data were analyzed using Cox proportional hazard model.
303 OSCC pts with full clinical data, and PD-L1 and p16 staining were evaluated. Median follow up was 55 months (2-184). Median age (range) was 59 years (34-85), 72% were male, 91% had WHO 0-1 performance status, 55% were current smokers. All had primary RT, 66-68Gy, 2Gy/fx, 6 fx/wk, and 3% had concomitant cisplatin. 81% were UICC 7 stage 3-4 tumors. 55% were p16+. 76% were PD-L1+ by CPS, 35% by TPS, and 31% by MIDS. TPS was significantly associated with MIDS (Chi square p = 0.003). p16 was a strong prognostic factor for loco-regional control [crude hazard ratio (HR) of 0.31 (95% CI: 0.21-0.49)], disease-specific survival [0.39 (0.26-0.57)] and overall survival [0.34 (0.25-0.46)]. PD-L1 expressed as CPS, TPS or MIDS, was not prognostic of the clinical endpoints, overall or by p16 status. Adjustment for other covariates did not change the results.
PD-L1 expression is not prognostic in localized or locally advanced OSCC, including p16 positive disease. p16 is affirmed the strongest biological prognostic factor in OSCC.
Clinical trial identification
Legal entity responsible for the study
The Danish Head and Neck Cancer Group (DAHANCA).
Merck & Co, Inc.
T. Steiniche: Research funding: Merck & Co, Inc. P-T. Vo, D.R. Chirovsky: Employement, stock ownership, research funding, travel and accommodations expenses: Merck & Co, Inc. J. Cheng: Employment, stock ownership: Merck & Co. D. Aurora-Garg, R. Swaby: Employment Merck & Co. All other authors have declared no conflicts of interest.