Abstract
BackgroundAt present, the prognostic significance of programmed cell death receptor ligand 1 (PD-L1) expression in oropharyngeal squamous cell carcinoma (OPSCC) patients is still controversial. In this study, we aim to synthesize relevant studies that have assessed the prognostic value of PD-L1 in patients with primary OPSCC treated according to the current standard-of-care.MethodsA systematic search of Medline/PubMed, Cochrane, Embase, Web of Science, and Scopus was conducted to define the prognostic role of PD-L1 expression in OPSCC. All studies published before July 31, 2021 were screened. Summary hazard ratios (sHR) with 95% confidence intervals (CIs) were calculated using a random-effects model.ResultsA total of 1522 OPSCC patients from 12 studies were included. PD-L1 expression in OPSCC tumor cells (TCs) was significantly associated with longer overall survival (sHR=0.63, 95% CI 0.50-0.79), and progression-free survival (sHR=0.62, 95% CI 0.49-0.79). A benefit in survival was also observed in PD-L1-positive OPSCC patients who underwent surgery (sHR=0.34, 95% CI 0.18-0.65). Finally, although PD-L1-positive expression was related to better outcomes both in HPV-negative and HPV-positive OPSCC, the difference reached the statistical significance only in the HPV-positive subgroup (sHR=0.37, 95% CI 0.19-0.73). No heterogeneity emerged between studies for all considered outcomes, with I 2 ranging from 0% for progression-free survival to 11% for overall survival.ConclusionsPD-L1 expression on TCs associated with improved survival in OPSCC. In particular, HPV-positive OPSCC most benefited from PD-L1 expression when compared to the PD-L1 negative counterpart. Thus, PD-L1 might represent a useful biomarker to stratify prognosis in OPSCC in addition to HPV status.
Highlights
Despite its high immunogenicity, tumor microenvironment (TME) of both primary and recurrent head and neck squamous cell carcinoma (HNSCC) is associated with pronounced immunosuppressive activity [1]
programmed death ligand 1 (PD-L1) binds to the programmed death 1 (PD-1), a negative co-stimulatory receptor that inhibits the activation of a wide range of immune cells, including peripherally activated T cells, B cells, monocytes, natural killer cells, and certain dendritic cells, playing a crucial role in the maintenance of immune tolerance of selfantigens [4, 5]
The primary outcome of this meta-analysis was to investigate the prognostic value of PD-L1 for overall survival (OS), progression-free survival (PFS), and loco-regional control (LRC) in patients treated by upfront surgery orradiotherapy for oropharyngeal squamous cell carcinoma (OPSCC)
Summary
Tumor microenvironment (TME) of both primary and recurrent head and neck squamous cell carcinoma (HNSCC) is associated with pronounced immunosuppressive activity [1]. PD-L1 binds to the programmed death 1 (PD-1), a negative co-stimulatory receptor that inhibits the activation of a wide range of immune cells, including peripherally activated T cells, B cells, monocytes, natural killer cells, and certain dendritic cells, playing a crucial role in the maintenance of immune tolerance of selfantigens [4, 5]. Blocking these ICI has become an important direction of immunotherapy with antibodies targeting PD-1 or PD-L1 being currently approved for the treatment of multiple cancers including HNSCC [6]. We aim to synthesize relevant studies that have assessed the prognostic value of PD-L1 in patients with primary OPSCC treated according to the current standard-of-care
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