Prognostic Significance of PD-L1 Expression In Patients With Primary Oropharyngeal Squamous Cell Carcinoma: A Meta-Analysis

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 I2 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.

Prognostic value of tumor-infiltrating immune cells and immune checkpoints in elderly head-and-neck squamous cell carcinoma patients undergoing definitive (chemo)radiotherapy

“…In another study, only high PD-L1 expression on immune cells but not on tumor cells was found to correspond with superior survival in HNSCC patients receiving surgery [ 29 ]. A recent meta-analysis showed favorable outcomes regarding increased tumoral PD-L1 expression in oropharyngeal cancer patients, both after surgery and primary (chemo)radiotherapy [ 27 ]. In line with the result of this meta-analysis, our study (in which more than 40% of patients suffered from oropharyngeal cancer) showed favorable LRC rates in patients with positive TPS.…”

“…There are conflicting data regarding the prognostic value of tumoral PD-L1 expression in HNSCC [24][25][26][27][28][29][30][31]. Within a multicenter study of the German Cancer Consortium Radiation Oncology Group, Balermpas et al showed a positive relationship between elevated PD-L1 expression and survival in locally advanced HNSCC patients treated by postoperative chemoradiotherapy [25].…”

“…Previous analyses and systematic meta-analyses have shown that higher levels of tumor-infiltrating lymphocytes (TILs), especially CD3 + and CD8 + TILs, are associated with improved survival in HNSCC patients receiving (chemo)radiotherapy [16][17][18][19][20][21][22][23]. In contrast, the prognostic role of immune checkpoints (ICs) for HNSCC patients undergoing radiotherapy is less clear [24][25][26][27][28][29][30][31]. Nevertheless, the tumoral PD-L1 status may become more relevant in the future considering clinical approaches combining (chemo)radiotherapy with IC inhibitors [32].…”

Single-cell analysis of myeloid cells in HPV+ tonsillar cancer

“…Biomarkers associated with the immune compartment of the tumor microenvironment (TME) have shown prognostic value in HPV + TC. For instance, several studies have highlighted a correlation between tumor-infiltrating CD8 + T-cells, T regulatory cells (Tregs) ( 5 , 6 ), and PD-L1 expression ( 7 , 8 ), respectively, to clinical outcome. However, immune-checkpoint blockade strategies, aiming at inducing T-cell responses, have shown limited clinical efficacy in HNCs, irrespective of HPV status ( 9 , 10 ).…”

Prognostic value of PD-1, PD-L1 and PD-L2 deserves attention in head and neck cancer

“…Among them, PD-L1 is not only a guidance for the use of immune checkpoint inhibitors (ICIs) (7), but also a potential prognostic indicator for head and neck cancer. Although studies on the prognosis of PD-L1 expression in head and neck cancer emerge one after another, the conclusions are controversial, and even the conclusions of some meta-analyses including large sample data are inconsistent (8)(9)(10)(11)(12)(13)(14). Meanwhile, PD-L2 is another important receptor of PD-1, and its binding affinity to PD-1 is about 2-6 times higher than that of PD-L1 (15).…”