Significant association of PD-L1 expression with human papillomavirus positivity and its prognostic impact in oropharyngeal cancer

Background: The programmed death pathway plays a role in persistent human papillomavirus (HPV) infection as well as in resistance to immune elimination during malignant progression. In this study, we examined PD-L1 expression by immunohistochemistry and tumour infiltrating lymphocytes (TIL) in 214 patients with oropharyngeal squamous cell cancer (OPSCC) to assess its clinical significance. Results: HPV-positive OPSCC were significantly more likely to express PD-L1 than HPV-negative OPSCC (85.2% vs 57.1%, p < 0.05). PD-Ll staining was more likely to be associated with TILs in HPV-positive OPSCC (67.9% vs 49.6%, p = 0.01). Relative to those patients with HPV-positive/PD-L1-positive OPSCC, patients with HPV negative/PD-L1 negative OPSCC were 6.4 times more likely to develop a local recurrence, 5.8 times more likely to develop an event and 6.5 times more likely to die. Within the HPV positive cases, PD-L1 expression also significantly impacted on the outcomes with PD-L1 negative cases more likely to develop a locoregional recurrence (HR 4.16), to have an event (HR 2.5) and to die (HR 3.16). Evidence of an interaction between HPV status and PD-L1 expression was found for overall survival (p < 0.005). Conclusion: Our findings suggested that different immune profiles in oropharyngeal cancer by HPV status and the effect of HPV on the outcomes is modified by PD-L1 expression.