Prognostic impact of PD-L1 in oropharyngeal cancer after primary curative radiotherapy and relation to HPV and tobacco smoking.

Incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rising rapidly in many western countries due to (HPV) and tobacco smoking, with a considerable overlap. Immunotherapy directed at the PD1/PD-L1 axis have shown promise in head and neck cancer and other cancer types. PD-L1 expression may indicate a poorer prognosis, and at the same time indicate a possible benefit of anti-PD-L1 immunotherapeutic agents. The primary aim of this study was to establish the prognostic effect of PD-L1 expression after primary curative radiotherapy alone. A cohort of 303 OPSCC patients treated with primary, curative intended radiotherapy was established. PD-L1 expression was evaluated by immunohistochemistry on formalin fixed, paraffin embedded tissue sections. PD-L1 positivity was defined as a Combined Positive Score (CPS) ≥1, indicating staining of either tumor cells, lymphocytes or macrophages. Median follow-up was 5.3 years. With 199 deaths, there was no difference in overall survival between patients with PD-L1+ and PD-L1- tumors (adjusted hazard ratio [aHR] and 95% confidence interval [CI]: 1.0 [0.71-1.4]). Also, locoregional failure was similar between the two groups (aHR 1.1 [CI: 0.68 - 1.7]). Tumors were PD-L1+ in 76% of cases, significantly more among HPV p16+ tumors (82% vs. 70%,  = .01). Interestingly, higher prevalence of PD-L1+ expression was seen in HPV p16+ patients with <10 pack-years of tobacco-smoking (93%) compared to HPV p16+ smokers (76%) or HPV p16-negative patients (70%) ( = .003). PD-L1 expression had no prognostic significance in OPSCC patients treated with primary radiotherapy alone. A substantial proportion of OPSCC tumors show PD-L1 overexpression, especially in HPV p16+ tumors in patients with little or no smoking history.