Multimedialna platforma wiedzy medycznej Internetowa Księgarnia Medyczna Kalendarium Konferencji
Ginekologia Polska
MENU
Shortcuts Submit an article Author Guidelines Ahead Of Print Reviewers 2023

open access

Vol 93, No 10 (2022)
Research paper
Published online: 2022-08-12
View PDF Download PDF file View HTML
Get Citation

Predictive values of PD‑L1 expression for survival outcomes in patients with cervical cancer: a systematic review and meta-analysis

Ting Hu1, Xiaoli Wan2, Haijing Wu1, Xinghan Cheng1, Shiqiang Xu1
DOI: 10.5603/GP.a2022.0071
·
Pubmed: 35984342
·
Ginekol Pol 2022;93(10):767-774.
Affiliations
  1. Department of Gynaecological Oncology, Sichuan Cancer Hospital (Sichuan Cancer Hospital & Institute), Chengdu, Sichuan Province, PR China
  2. Department of Gynecology, People's Hospital of Leshan, Leshan, Sichuan Province, PR China

open access

Vol 93, No 10 (2022)
ORIGINAL PAPERS Gynecology
Published online: 2022-08-12

Abstract

Objectives: Cervical cancer is one of the most common cancers in women worldwide. Although mortality has declined over the past 30 years in high-income areas, it remains a problem in several countries. Given that the prognosis of patients with recurrent or metastatic disease is poor, it is necessary to identify valuable predictive indicators to estimate survival outcomes in patients with cervical cancer.
Material and methods: We searched electronic databases such as PubMed, Web of Science, Embase, Ovid MEDLINE, and the Cochrane Central Register of Controlled Trials, and investigated the relationship between Programmed death-ligand 1(PD-L1) expression and prognosis. Chi squared tests and I2 were utilized to assess study heterogeneity, and publication bias was estimated using Begg’s funnel plot and Egger linear regression test.
Results: Thirteen eligible studies with 1422 patients were included. Generally, high PD-L1 expression was conclusively associated with poor overall survival (OS) (HR: 1.31; 95% CI 1.03–1.66, p = 0.025). However, PD-L1 expression demonstrated no association with progression-free survival (HR: 0.93; 0.73–1.19, p = 0.57). High PD-L1 expression with a sample size over 100 indicated a shorter OS (HR: 1.51; 95% CI 1.13–2.01). High expression of PD-L1 in Asians represented a lower OS (HR: 1.52; 1.14–2.03). Overexpression of PD-L1 in tumor cells (HR: 1.57; 1.29–2.10) and tumor-infiltrating immune cells (HR: 1.75; 1.02-2.99) predicted poor OS. High PD-L1 expression (HR: 4.04; 2.58–6.31) showed a lower effect on OS with a cut-off value of 5%.
Conclusions: Our results indicate that high PD-L1 expression could be a valuable biomarker for predicting clinical outcomes in patients with cervical cancer.

Abstract

Objectives: Cervical cancer is one of the most common cancers in women worldwide. Although mortality has declined over the past 30 years in high-income areas, it remains a problem in several countries. Given that the prognosis of patients with recurrent or metastatic disease is poor, it is necessary to identify valuable predictive indicators to estimate survival outcomes in patients with cervical cancer.
Material and methods: We searched electronic databases such as PubMed, Web of Science, Embase, Ovid MEDLINE, and the Cochrane Central Register of Controlled Trials, and investigated the relationship between Programmed death-ligand 1(PD-L1) expression and prognosis. Chi squared tests and I2 were utilized to assess study heterogeneity, and publication bias was estimated using Begg’s funnel plot and Egger linear regression test.
Results: Thirteen eligible studies with 1422 patients were included. Generally, high PD-L1 expression was conclusively associated with poor overall survival (OS) (HR: 1.31; 95% CI 1.03–1.66, p = 0.025). However, PD-L1 expression demonstrated no association with progression-free survival (HR: 0.93; 0.73–1.19, p = 0.57). High PD-L1 expression with a sample size over 100 indicated a shorter OS (HR: 1.51; 95% CI 1.13–2.01). High expression of PD-L1 in Asians represented a lower OS (HR: 1.52; 1.14–2.03). Overexpression of PD-L1 in tumor cells (HR: 1.57; 1.29–2.10) and tumor-infiltrating immune cells (HR: 1.75; 1.02-2.99) predicted poor OS. High PD-L1 expression (HR: 4.04; 2.58–6.31) showed a lower effect on OS with a cut-off value of 5%.
Conclusions: Our results indicate that high PD-L1 expression could be a valuable biomarker for predicting clinical outcomes in patients with cervical cancer.

Full Text:

View PDF Download PDF file View HTML
Get Citation

Keywords

biomarkers; cervical cancer; diagnosis; immune cells; PD-L1

About this article
Title

Predictive values of PD‑L1 expression for survival outcomes in patients with cervical cancer: a systematic review and meta-analysis

Journal

Ginekologia Polska

Issue

Vol 93, No 10 (2022)

Article type

Research paper

Pages

767-774

Published online

2022-08-12

Page views

4055

Article views/downloads

615

DOI

10.5603/GP.a2022.0071

Pubmed

35984342

Bibliographic record

Ginekol Pol 2022;93(10):767-774.

Keywords

biomarkers
cervical cancer
diagnosis
immune cells
PD-L1

Authors

Ting Hu
Xiaoli Wan
Haijing Wu
Xinghan Cheng
Shiqiang Xu

References (41)
  1. Sung H, Ferlay J, Siegel RL, 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): 209–249.
    CrossRefPubMed
  2. Cohen P, Jhingran A, Oaknin A, et al. Cervical cancer. The Lancet. 2019; 393(10167): 169–182.
    CrossRef
  3. Pfaendler KS, Tewari KS. Changing paradigms in the systemic treatment of advanced cervical cancer. Am J Obstet Gynecol. 2016; 214(1): 22–30.
    CrossRefPubMed
  4. Hansen JD, Du Pasquier L, Lefranc MP, et al. The B7 family of immunoregulatory receptors: a comparative and evolutionary perspective. Mol Immunol. 2009; 46(3): 457–472.
    CrossRefPubMed
  5. Jiang X, Wang J, Deng X, et al. Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape. Mol Cancer. 2019; 18(1): 10.
    CrossRefPubMed
  6. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012; 12(4): 252–264.
    CrossRefPubMed
  7. Blank C, Mackensen A. Contribution of the PD-L1/PD-1 pathway to T-cell exhaustion: an update on implications for chronic infections and tumor evasion. Cancer Immunol Immunother. 2007; 56(5): 739–745.
    CrossRefPubMed
  8. Brown JA, Dorfman DM, Ma FR, et al. Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. J Immunol. 2003; 170(3): 1257–1266.
    CrossRefPubMed
  9. Pennock GK, Chow LQM. The Evolving Role of Immune Checkpoint Inhibitors in Cancer Treatment. Oncologist. 2015; 20(7): 812–822.
    CrossRefPubMed
  10. Wang C, Zhu H, Zhou Y, et al. Prognostic Value of PD-L1 in Breast Cancer: A Meta-Analysis. Breast J. 2017; 23(4): 436–443.
    CrossRefPubMed
  11. Qu HX, Zhao LP, Zhan SH, et al. Clinicopathological and prognostic significance of programmed cell death ligand 1 (PD-L1) expression in patients with esophageal squamous cell carcinoma: a meta-analysis. J Thorac Dis. 2016; 8(11): 3197–3204.
    CrossRefPubMed
  12. Shi T, Zhu S, Guo H, et al. The Impact of Programmed Death-Ligand 1 Expression on the Prognosis of Early Stage Resected Non-Small Cell Lung Cancer: A Meta-Analysis of Literatures. Front Oncol. 2021; 11: 567978.
    CrossRefPubMed
  13. Zhuan-Sun Y, Huang F, Feng M, et al. Prognostic value of PD-L1 overexpression for pancreatic cancer: evidence from a meta-analysis. Onco Targets Ther. 2017; 10: 5005–5012.
    CrossRefPubMed
  14. Li Y, Huang Q, Zhou Y, et al. The Clinicopathologic and Prognostic Significance of Programmed Cell Death Ligand 1 (PD-L1) Expression in Patients With Prostate Cancer: A Systematic Review and Meta-Analysis. Front Pharmacol. 2018; 9: 1494.
    CrossRefPubMed
  15. Kim M, Kim H, Suh DH, et al. Identifying Rational Candidates for Immunotherapy Targeting PD-1/PD-L1 in Cervical Cancer. Anticancer Res. 2017; 37(9): 5087–5094.
    CrossRefPubMed
  16. Kawachi A, Yoshida H, Kitano S, et al. Tumor-associated CD204 M2 macrophages are unfavorable prognostic indicators in uterine cervical adenocarcinoma. Cancer Sci. 2018; 109(3): 863–870.
    CrossRefPubMed
  17. Begg C, Mazumdar M. Operating Characteristics of a Rank Correlation Test for Publication Bias. Biometrics. 1994; 50(4): 1088.
    CrossRef
  18. Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997; 315(7109): 629–634.
    CrossRefPubMed
  19. Karim R, Jordanova ES, Piersma SJ, et al. Tumor-expressed B7-H1 and B7-DC in relation to PD-1+ T-cell infiltration and survival of patients with cervical carcinoma. Clin Cancer Res. 2009; 15(20): 6341–6347.
    CrossRefPubMed
  20. Enwere EK, Kornaga EN, Dean M, et al. Expression of PD-L1 and presence of CD8-positive T cells in pre-treatment specimens of locally advanced cervical cancer. Mod Pathol. 2017; 30(4): 577–586.
    CrossRefPubMed
  21. Feng M, Xu L, He Y, et al. Clinical significance of PD-L1 (CD274) enhanced expression in cervical squamous cell carcinoma. Int J Clin Exp Pathol. 2018; 11(11): 5370–5378.
    PubMed
  22. Kawachi A, Yoshida H, Kitano S, et al. Tumor-associated CD204 M2 macrophages are unfavorable prognostic indicators in uterine cervical adenocarcinoma. Cancer Sci. 2018; 109(3): 863–870.
    CrossRefPubMed
  23. Wang S, Li J, Xie J, et al. Programmed death ligand 1 promotes lymph node metastasis and glucose metabolism in cervical cancer by activating integrin β4/SNAI1/SIRT3 signaling pathway. Oncogene. 2018; 37(30): 4164–4180.
    CrossRefPubMed
  24. Chung HC, Ros W, Delord JP, et al. Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2019; 37(17): 1470–1478.
    CrossRefPubMed
  25. Grochot RM, Brollo J, Neto FR, et al. Expression of PD-L1 in cervical carcinoma and its impact on survival associated with T-cell infiltration and FoxP3 expression. Cancer Manag Res. 2019; 11: 4597–4605.
    CrossRefPubMed
  26. Tamura K, Hasegawa K, Katsumata N, et al. Efficacy and safety of nivolumab in Japanese patients with uterine cervical cancer, uterine corpus cancer, or soft tissue sarcoma: Multicenter, open-label phase 2 trial. Cancer Sci. 2019; 110(9): 2894–2904.
    CrossRefPubMed
  27. Chen H, Xia B, Zheng T, et al. Immunoscore system combining CD8 and PD-1/PD-L1: A novel approach that predicts the clinical outcomes for cervical cancer. Int J Biol Markers. 2020; 35(1): 65–73.
    CrossRefPubMed
  28. Iijima M, Okonogi N, Nakajima NI, et al. Significance of PD-L1 expression in carbon-ion radiotherapy for uterine cervical adeno/adenosquamous carcinoma. J Gynecol Oncol. 2020; 31(2): e19.
    CrossRefPubMed
  29. Miyasaka Y, Yoshimoto Y, Murata K, et al. Treatment outcomes of patients with adenocarcinoma of the uterine cervix after definitive radiotherapy and the prognostic impact of tumor-infiltrating CD8+ lymphocytes in pre-treatment biopsy specimens: a multi-institutional retrospective study. J Radiat Res. 2020; 61(2): 275–284.
    CrossRefPubMed
  30. Tsuchiya T, Someya M, Takada Yu, et al. Association between radiotherapy-induced alteration of programmed death ligand 1 and survival in patients with uterine cervical cancer undergoing preoperative radiotherapy. Strahlenther Onkol. 2020; 196(8): 725–735.
    CrossRefPubMed
  31. Gu X, Dong M, Liu Z, et al. Elevated PD-L1 expression predicts poor survival outcomes in patients with cervical cancer. Cancer Cell Int. 2019; 19: 146.
    CrossRefPubMed
  32. Chung HC, Ros W, Delord JP, et al. Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2019; 37(17): 1470–1478.
    CrossRefPubMed
  33. Rischin D, Gil-Martin M, González-Martin A, et al. PD-1 blockade in recurrent or metastatic cervical cancer: Data from cemiplimab phase I expansion cohorts and characterization of PD-L1 expression in cervical cancer. Gynecol Oncol. 2020; 159(2): 322–328.
    CrossRefPubMed
  34. Tuyaerts S, Van Nuffel AnMT, Naert E, et al. PRIMMO study protocol: a phase II study combining PD-1 blockade, radiation and immunomodulation to tackle cervical and uterine cancer. BMC Cancer. 2019; 19(1): 506.
    CrossRefPubMed
  35. Santin AD, Deng W, Frumovitz M, et al. Phase II evaluation of nivolumab in the treatment of persistent or recurrent cervical cancer (NCT02257528/NRG-GY002). Gynecol Oncol. 2020; 157(1): 161–166.
    CrossRefPubMed
  36. Jung KH, LoRusso P, Burris H, et al. Phase I Study of the Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Navoximod (GDC-0919) Administered with PD-L1 Inhibitor (Atezolizumab) in Advanced Solid Tumors. Clin Cancer Res. 2019; 25(11): 3220–3228.
    CrossRefPubMed
  37. Liu JF, Gray KP, Wright AA, et al. Results from a single arm, single stage phase II trial of trametinib and GSK2141795 in persistent or recurrent cervical cancer. Gynecol Oncol. 2019; 154(1): 95–101.
    CrossRefPubMed
  38. Rotman J, Mom CH, Jordanova ES, et al. 'DURVIT': a phase-I trial of single low-dose durvalumab (Medi4736) IntraTumourally injected in cervical cancer: safety, toxicity and effect on the primary tumour- and lymph node microenvironment. BMC Cancer. 2018; 18(1): 888.
    CrossRefPubMed
  39. Ni X, Sun X, Wang D, et al. The clinicopathological and prognostic value of programmed death-ligand 1 in colorectal cancer: a meta-analysis. Clin Transl Oncol. 2019; 21(5): 674–686.
    CrossRefPubMed
  40. Gu L, Chen M, Guo D, et al. PD-L1 and gastric cancer prognosis: A systematic review and meta-analysis. PLoS One. 2017; 12(8): e0182692.
    CrossRefPubMed
  41. Zhang C, Yang Q. Predictive Values of Programmed Cell Death-Ligand 1 Expression for Prognosis, Clinicopathological Factors, and Response to Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Inhibitors in Patients With Gynecological Cancers: A Meta-Analysis. Front Oncol. 2020; 10: 572203.
    CrossRefPubMed

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By VM Media Group sp. z o.o., ul. Świętokrzyska 73, 80–180 Gdańsk
tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl