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

Background: Incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rising rapidly in many western countries due to Human papillomavirus (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. Material and methods: 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. Results: 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%, p = .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%) (p = .003). Conclusion: 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.