Unveiling the role of Programmed Cell Death Ligand-1 (PDL-1) expression in cervical squamous cell carcinoma: Clinical insights and pathological implications
Keywords:
Squamous cell carcinoma, PD-L1, Cervical, HPV, IHCAbstract
Background: Squamous Cell Carcinoma Cervix (SCC) is a major contributor to cancer-related mortality, closely linked to chronic HPV infection. Programmed Cell Death Ligand-1 (PD-L1) has surfaced as a prospective biomarker in several cancers, including cervical squamous cell carcinoma (SCC); however, its clinical and pathological relevance in untreated patients has not yet been thoroughly investigated.
Methods: This cross-sectional study included 66 untreated patients diagnosed with cervical SCC, with clinicopathological data and formalin-fixed paraffin-embedded tissue samples collected from Universitas Hasanuddin Teaching Hospital. PD-L1 expression was evaluated using the Tumor Proportion Score (TPS) and categorized as negative (<1%), weakly positive (1–9%), and strongly positive (≥10%). Bivariate methods were used to investigate at the associations between PD-L1 expression and tumor characteristics including stage, differentiation, lymphovascular space invasion (LVSI), and tumor size.
Results: Strong PD-L1 expression (≥10%) was significantly more frequent in locally advanced and metastatic stages (p = 0.036). The highest level of PD-L1 expression was observed in tumors which were poorly differentiated; Whereby 84.9% of these tumors exhibited strong expression. No significant correlation was found between PD-L1 expression and LVSI or tumor size. Host factors including age, sexual history, parity, and contraceptive use demonstrated no correlation with PD-L1 expression.
Conclusion: The study showed that PD-L1 expression is associated with advanced stages and poor differentiation in cervical SCC, pointing to its potential role in guiding future treatment decisions
References
References
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. 2023;71(3):209-249. doi:10.3322/caac.21660
2. International Agency for Research on Cancer Global Cancer Observatory. Cervical cancer incidence and mortality statistics in Indonesia. 2020. Available from: https://gco.iarc.fr/today/data/factsheets/populations/360-indonesia-fact-sheets.pdf
3. World Health Organization Human papillomavirus (HPV) and cervical cancer. WHO Fact Sheet. 2022. Available from: https://www.who.int/news-room/fact-sheets/detail/cervical-cancer
4. Arbyn M, Weiderpass E, Bruni L, et al Estimates of incidence and mortality of cervical cancer in 2018: A worldwide analysis. Lancet. 2020;385(9961):1001-1011. doi:10.1016/S0140-6736(15)60636-0
5. Garcia C, Ring KL, Lemech C, et al Programmed cell death ligand-1 (PD-L1) and its role in immune evasion in cancer. Nat Rev Immunol. 2018;18(7):439-449. doi:10.1038/s41577-018-0005-4
6. Heeren AM, Punt S, Bleeker MC, et al Prognostic effect of PD-L1 expression in cervical cancer. Cancer Immunol Res. 2016;4(3):225-234. doi:10.1158/2326-6066.CIR-15-0174
7. Liu X, Liu B, Li J, et al HPV E6 and E7 oncoproteins in cervical cancer progression. J Clin Oncol. 2017;35(1):28-34.
8. Singh R Multiparity and cervical cancer risk: A review of epidemiological studies. Asian Pac J Cancer Prev. 2023;24(7):1905-1912. doi:10.31557/APJCP.2023.24.7.1905
9. Koliopoulos G, Nyaga VN, Santesso N, et al Cytology versus HPV testing for cervical cancer screening in the general population. Int J Cancer. 2018;143(5):1030-1040. doi:10.1002/ijc.31373
10. Huang J, Olawaiye AB, Clark LH, et al Pembrolizumab in cervical cancer: Results from KEYNOTE-158. Lancet Oncol. 2022;23(5):639-649. doi:10.1016/S1470-2045(22)00070-0
11. Marabelle A, Fakih M, Lopez J, et al Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: Results from the KEYNOTE-158 study. J Clin Oncol. 2020;38(28):3284-3292. doi:10.1200/JCO.19.02105
12. Choi YJ, Park JS HPV and cervical cancer: Epidemiology and prevention. Int J Gynaecol Obstet. 2016;134(2):216-220. doi:10.1016/j.ijgo.2015.11.021
13. Ghosh A, Kumar S, Kumar A Immune evasion in cancer and implications for immunotherapy. JAMA Oncol. 2021;7(8):1145-1152. doi:10.1001/jamaoncol.2021.1234
14. Campos-Parra AD, Maffuz-Aziz A, Arrieta O The role of the tumor microenvironment in cervical cancer: Implications for immunotherapy. Cerv Cancer J. 2022;10(2):220-230.
15. Lantuejoul S, Sound-Tsao M, Cooper WA, et al PD-L1 testing for lung cancer in 2019: Perspective from the IASLC pathology committee. Eur Respir J. 2020;55(2):1901403. doi:10.1183/13993003.01403-2019
16. Brito MJ, Carvalho A, Medeiros R Immune microenvironment and PD-L1 expression in cervical cancer. J Cancer Immunol. 2023;22(4):340-352.
17. Feng Z, Wen H, Ju X Tumor-infiltrating lymphocytes and PD-L1 expression in cervical cancer. Int J Gynecol Cancer. 2018;28(8):1554-1563. doi:10.1097/IGC.0000000000001354
18. Rotman Y, Brown M, Rosenthal A Immune microenvironment and PD-L1 in cervical cancer. J Cancer Res Clin Oncol. 2020;146(9):2403-2411. doi:10.1007/s00432-020-03292-2
19. Wu L, Saxena S, Awaji M Checkpoint inhibitors and tumor immunity: Mechanisms and clinical implications. Front Immunol. 2019;10:1225. doi:10.3389/fimmu.2019.01225
20. Reddy S, Zhuang Y, Kaur P The role of PD-L1 in cervical cancer: An emerging immunotherapy target. J Immunother. 2017;39(6):129-139.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Yuniarni Sulistiawati, Sharvianty Arifuddin, Syahruni Syahrir, Rina Masadah, Andi Alfian Zainuddin

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers.
Authors retain the copyright for their published work. No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.

