Iranian Journal of Pathology

Evaluation of Programmed Death - Ligand 1 (Pd-L1) Expression in Head and Neck Squamous Cell Carcinoma

Document Type : Original Research

Authors

Aarya Unnikrishnan
Vijaya Basavaraj

Department of Pathology, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India

https://doi.org/10.30699/ijp.2023.1988955.3057
Abstract
Background & Objective: Head and Neck Squamous Cell Carcinoma (HNSCC) is a highly frequent malignancy worldwide and is also the leading cause of death. The prognosis for individuals with HNSCC remains dismal, with a five-year survival rate of less than 50%. The novel anti-PD-L1 immunotherapy is found to be promising, and immunohistochemistry (IHC) has been established as a reliable method for patient stratification. We intend to evaluate the prognostic significance of the expression of programmed death ligand-1 (PD-L1) in HNSCC and determine its association with clinicopathological variables.
Methods: A total of 50 cases of biopsy-confirmed HNSCC were studied in a tertiary hospital between Dec 2020 and June 2022. The specimens were tested for PD-L1 IHC expression with antibody clone CAL-10 (Biocare) and scored by Combined Positive Score (CPS). The association between PD-L1 expression and clinicopathological variables was evaluated.
Results: PD-L1 was positive in 92% of the cases, and a significant association (P= 0.024) was seen between PD-L1 expression and tumor-infiltrating lymphocytes (TILs). PD-L1 did not show any significant association with patient demographics, tumor site, grade, or stage.
Conclusion: In the present study, evaluation of the immunohistochemical expression of PD-L1 on the tumor cells and TILs in HNSCC revealed a high prevalence of PD-L1 expression. PD-L1 IHC studies for patient selection for immunotherapy would be a promising technique. Frequent PD-L1 expression in tumors with significant TILs may be useful in identifying patients who may benefit from anti-PD-1/PD-L1 therapy.

Keywords

Head and neck
Programmed death ligand-1
Squamous cell carcinoma
Tumor-infiltrating lymphocytes

Subjects

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-49. [DOI:10.3322/caac.21660] [PMID]
  2. Qiao XW, Jiang J, Pang X, Huang MC, Tang YJ, Liang XH, Tang YL. The evolving landscape of PD-1/PD-L1 pathway in head and neck cancer. Front Immunol. 2020 Sep 18;11:1721. [DOI:10.3389/fimmu.2020.01721] [PMID] [PMCID]
  3. Tang H, Zhou X, Ye Y, Zhou Y, Wu C, Xu Y. The different role of PD-L1 in head and neck squamous cell carcinomas: a meta-analysis. Pathology-Res. Pract. 2020;216(1):152768. [DOI:10.1016/j.prp.2019.152768] [PMID]
  4. Johnson DE, Burtness B, Leemans CR, Lui VW, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nat Rev Dis Primers. 2020;6(1):1-22. [DOI:10.1038/s41572-020-00224-3] [PMID] [PMCID]
  5. Chen SW, Li SH, Shi DB, Jiang WM, Song M, Yang AK, et al. Expression of PD-1/PD-L1 in head and neck squamous cell carcinoma and its clinical significance. Int J Biol Markers. 2019;34(4):398-405. [DOI:10.1177/1724600819884722] [PMID]
  6. Davis AA, Patel VG. The role of PD-L1 expression as a predictive biomarker: an analysis of all US Food and Drug Administration (FDA) approvals of immune checkpoint inhibitors. J Immunotherapy Cancer. 2019;7(1):1-8. [DOI:10.1186/s40425-019-0768-9] [PMID] [PMCID]
  7. Rollins MR, Gibbons Johnson RM. CD80 expressed by CD8+ T cells contributes to PD-L1-induced apoptosis of activated CD8+ T cells. J Immunol Res. 2017;2017. [DOI:10.1155/2017/7659462] [PMID] [PMCID]
  8. Chen RY, Lin YC, Shen WC, Hsieh TC, Yen KY, Chen SW,et al. Associations of tumor PD-1 ligands, immunohistochemical studies, and textural features in 18F-FDG PET in squamous cell carcinoma of the head and neck. Sci Rep. 2018;8(1):1-0. [DOI:10.1038/s41598-017-18489-2] [PMID] [PMCID]
  9. Park JC, Krishnakumar HN, Saladi SV. Current and Future Biomarkers for Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinoma. Curr Oncol. 2022;29(6):4185-98. [DOI:10.3390/curroncol29060334] [PMID] [PMCID]
  10. Dako A. PD-L1 IHC 22C3 pharmDx Interpretation Manual-Head and Neck Squamous Cell Carcinoma (HNSCC).
  11. Guerini Rocco E, Eccher A, Girolami I, Graziano P, Fontanini G, Vigliar E, et al. Concordance between Three PD-L1 Immunohistochemical Assays in Head and Neck Squamous Cell Carcinoma (HNSCC) in a Multicenter Study. Diagnostics. 2022;12(2):477. [DOI:10.3390/diagnostics12020477] [PMID] [PMCID]
  12. Müller T, Braun M, Dietrich D, Aktekin S, Höft S, Kristiansen G, et al. PD-L1: a novel prognostic biomarker in head and neck squamous cell carcinoma. Oncotarget. 2017;8(32):52889-900. [DOI:10.18632/oncotarget.17547] [PMID] [PMCID]
  13. Schneider S, Kadletz L, Wiebringhaus R, Kenner L, Selzer E, Füreder T, et al. PD-1 and PD-L1 expression in HNSCC primary cancer and related lymph node metastasis - impact on clinical outcome. Histopathology. 2018 Oct;73(4):573-84. [DOI:10.1111/his.13646] [PMID]
  14. Kim HS, Lee JY, Lim SH, Park K, Sun JM, Ko YH, et al. Association Between PD- L1 and HPV Status and the Prognostic Value of PD-L1 in Oropharyngeal Squamous Cell Carcinoma. Cancer Res Treat. 2016 Apr;48(2):527-36. [DOI:10.4143/crt.2015.249] [PMID] [PMCID]
  15. Mishra PS, Sidhu A, Dwivedi G, Mulajker DS, Awasthi S. Determining PD-L1 expression in head and neck squamous cell carcinoma using immunohistochemistry. Indian J Cancer. 2021 Jan 27.
  16. Mehra R, Seiwert TY, Gupta S, Weiss J, Gluck I, Eder JP, et al. Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE- 012. Br J Cancer. 2018;119(2):153-9. [DOI:10.1038/s41416-018-0131-9] [PMID] [PMCID]
  17. Wusiman D, Guo L, Huang Z, Li Z, Liu S, Ying J, et al. The clinicopathological significance of PD-L1 expression assessed by the combined positive score (CPS) in head and neck squamous cell carcinoma. Pathol Res Pract. 2022;236:153934. [DOI:10.1016/j.prp.2022.153934] [PMID]
  18. Ngamphaiboon N, Chureemas T, Siripoon T, Arsa L, Trachu N, Jiarpinitnun C, et al. Characteristics and impact of programmed death-ligand 1 expression,CD8+ tumor-infiltrating lymphocytes, and p16 status in head and neck squamous cell carcinoma. Med Oncol. 2019;36(2):1-0. [DOI:10.1007/s12032-018-1241-1] [PMID]
  19. Satgunaseelan L, Gupta R, Madore J, Chia N, Lum T, Palme CE, et al. Programmed cell death-ligand 1 expression in oral squamous cell carcinoma is associated with an inflammatory phenotype.Pathology.2016 Oct;48(6):574-80. [DOI:10.1016/j.pathol.2016.07.003] [PMID]
  20. Lenouvel D, González-Moles MÁ, Ruiz-Ávila I, Chamorro-Santos C, González-Ruiz L, González-Ruiz I, et al. Clinicopathological and prognostic significance of PD-L1 in oral cancer: A preliminary retrospective immunohistochemistry study. Oral Dis. 2021;27(2):173-82. [DOI:10.1111/odi.13509] [PMID]
  21. Hashim D, Genden E, Posner M, Hashibe M, Boffetta P. Head and neck cancer prevention: from primary prevention to impact of clinicians on reducing burden. Ann Oncol. 2019;30(5):744-56. [DOI:10.1093/annonc/mdz084] [PMID] [PMCID]
  22. Kim HR, Ha SJ, Hong MH, Heo SJ, Koh YW, Choi EC, et al. PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for head and neck cancer patients. Sci Rep. 2016 Nov 14;6(1):1-2. [DOI:10.1038/srep36956] [PMID] [PMCID]
  23. Kim, T., Jung S. H., Kim, S. K., & Kwon, H. J. (2019). P16 expression and its association with PD-L1 expression and FOXP3-positive tumor infiltrating lymphocytes in head and neck squamous cell carcinoma. Mol Cell Toxicol. 2019 Apr;15(2):137- 43. [DOI:10.1007/s13273-019-0017-9]
  24. Cadoni G, Giraldi L, Petrelli L, Pandolfini M, Giuliani M, Paludetti G, et al. Prognostic factors in head and neck cancer: a 10-year retrospective analysis in a single-institution in Italy. Acta Otorhinolaryngol Ital. 2017;37(6):458. [DOI:10.14639/0392-100X-1246] [PMID] [PMCID]
  25. Fu ZM, Zhang DJ, Guo YY, Han S, Guo F, Bai J et al. Expression of PDL1 and CD4+ tumor infiltrating lymphocytes predict survival in head and neck squamous cell carcinoma. Mol Clin Oncol. 2022 Mar 1;16(3):1-9. [DOI:10.3892/mco.2022.2492] [PMID] [PMCID]
  26. Almangush A, De Keukeleire S, Rottey S, Ferdinande L, Vermassen T, Leivo I, Mäkitie AA. Tumor-Infiltrating Lymphocytes in Head and Neck Cancer: Ready for Prime Time? Cancer. 2022 Mar 18;14(6):1558. [DOI:10.3390/cancers14061558] [PMID] [PMCID]
  27. Cho YA, Yoon HJ, Lee JI, Hong SP, Hong SD. Relationship between the expressions of PD-L1 and tumor-infiltrating lymphocytes in oral squamous cell carcinoma. Oral Oncol. 2011 Dec 1;47(12):1148-53. [DOI:10.1016/j.oraloncology.2011.08.007] [PMID]
  28. Cerbelli B, Girolami I, Eccher A, Costarelli L, Taccogna S, Scialpi R, et al. Evaluating programmed death-ligand 1 (PD-L1) in head and neck squamous cell carcinoma: concordance between the 22C3 PharmDx assay and the SP263 assay on whole sections from a multicentre study. Histopathology. 2022 Jan;80(2):397- 406. [DOI:10.1111/his.14562] [PMID] [PMCID]
  29. de Ruiter EJ, Mulder FJ, Koomen BM, Speel EJ, van den Hout MFCM, de Roest RH, et al. Comparison of three PD-L1 immunohistochemical assays in head and neck squamous cell carcinoma (HNSCC). Mod Pathol. 2021;34(6):1125-32. [DOI:10.1038/s41379-020-0644-7] [PMID]
  30. Taube JM, Klein A, Brahmer JR, Xu H, Pan X, Kim JH, et al. Association of PD-1, PD-1 Ligands, and Other Features of the Tumor Immune Microenvironment with Response to Anti-PD-1 Therapy. Clin. Cancer Res. 2014;20(19):5064-74. [DOI:10.1158/1078-0432.CCR-13-3271] [PMID] [PMCID]

31. Darvin P, Toor SM, Sasidharan Nair V, Elkord E. Immune checkpoint inhibitors: recent progress and potential biomarkers. Exp Mol Med. 2018;50(12):1-11. [DOI:10.1038/s12276-018-0191-1] [PMID] [PMCID.

Iranian Journal of Pathology
Volume 18, Issue 2
Spring 2023
Pages 193-201

  • Receive Date 13 February 2023
  • Revise Date 31 March 2023
  • Accept Date 03 June 2023

Home

Guide for Authors

Submit Manuscript

Contact Us