Skip to main content

Advertisement

SpringerLink
Log in

Programmed Death Ligand 1 (PD-L1) Expression in Cervical Cancer

  • Original Article
  • Published:
Indian Journal of Gynecologic Oncology Aims and scope Submit manuscript

Abstract

Objective

The objectives were to study the pattern of expression of PD-L1 in patients with carcinoma cervix and find out any relation with the various patient- and disease-related factors like histology, FIGO stage, lymph node metastasis and response to treatment.

Methods

One hundred cervical cancer patients registered during 2018 who were suitable for radical treatment were identified. The paraffin-embedded, formalin-fixed cervical biopsy specimens of these patients were collected. Immunohistochemical staining for PD-L1 expression was performed on the cervical biopsy material. The test was considered positive if 50 per cent or more tumour cells or less than 50 per cent with intense staining were present.

Results

PD-L1 was positive in 25 of 99 (25.3%) cervical carcinoma samples. PD-L1 was positive in 18 of 81 (22%) squamous cell carcinomas, 7 of 16 (43.7%) adenocarcinomas and 0 out of 2 adenosquamous carcinomas. Twenty-nine per cent of patients with positive pelvic nodes expressed PD-L1 positivity. None of the patients with paraaortic node metastasis expressed PD-L1 positivity. No statistically significant associations were found between PD-LI positivity and menopausal status, haemoglobin level, histology, tumour size, FIGO stage, nodal involvement and response to treatment.

Conclusions

One out of four patients had evidence of PD-L1 positivity in their cervical cancer. No association was found between PD-L1 expression and various clinicopathological factors and response to treatment. But follow-up studies are needed to observe any effect on disease-free or overall survival. Validation of scoring of PD-L1 expression and uniform reporting is required.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LAJA. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.

    Article  Google Scholar 

  2. Patel S, Chiplunkar S. Host immune responses to cervical cancer. Curr Opin Obstet Gynecol. 2009;21(1):54–9.

    Article  Google Scholar 

  3. Bosch FX, Lorincz A, Muñoz N, Meijer CJLM, Shah KV. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol. 2002;55(4):244–65.

    Article  CAS  Google Scholar 

  4. Herrington CS. Human papillomaviruses and cervical neoplasia. I. Classification, virology, pathology, and epidemiology. J Clin Pathol. 1994;47(12):1066–72.

  5. Pandya PH, Murray ME, Pollok KE, Renbarger JL. The immune system in cancer pathogenesis: potential therapeutic approaches. J Immunol Res. 2016;2016.

  6. Shiraki S, Yamada Y, Nakano T. Immunotherapy for uterine cervical carcinoma. Acta Obstet Gynaecol Jpn. 1979;31(11):2015.

    Google Scholar 

  7. Arends MJ, Buckley CH, Wells M. Aetiology, pathogenesis, and pathology of cervical neoplasia. J Clin Pathol. 1998;51(2):96–103.

    Article  CAS  Google Scholar 

  8. Berrington De González A, Sweetland S, Green J. Comparison of risk factors for squamous cell and adenocarcinomas of the cervix: a meta-analysis. Br J Cancer. 2004;90(9):1787–91.

  9. Reddy OL, Shintaku PI, Moatamed NA. Programmed death-ligand 1 (PD-L1) is expressed in a significant number of the uterine cervical carcinomas. Diagn Pathol. 2017;12(1):1–11.

    Article  CAS  Google Scholar 

  10. D’Incecco A, Andreozzi M, Ludovini V, Rossi E, Capodanno A, Landi L, et al. PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients. Br J Cancer. 2015;112(1):95–102.

    Article  Google Scholar 

  11. Retz M, Bedke J, Herrmann E, Grimm M-O, Zimmermann U, Müller L, et al. 845OPhase III randomized, sequential, open-label study to evaluate the efficacy and safety of sorafenib-pazopanib versus pazopanib-sorafenib in the treatment of metastatic renal cell carcinoma (SWITCH-II). Ann Oncol 2017;28(suppl_5):1–2.

  12. Carbone DP, Reck M, Creelan B, Horn L, Steins M, Felip E et al. HHS Public Access. 2019;376(25):2415–26.

  13. Ferris RL, Licitra L, Fayette J, Even C, Blumenschein G, Harrington KJ, et al. Nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: efficacy and safety in checkMate 141 by prior cetuximab use. Clin Cancer Res. 2019;25(17):5221–30.

    Article  CAS  Google Scholar 

  14. Mezache L, Paniccia B, Nyinawabera A, Nuovo GJ. Enhanced expression of PD L1 in cervical intraepithelial neoplasia and cervical cancers. Mod Pathol. 2015;28(12):1594–602.

    Article  CAS  Google Scholar 

  15. Patel SP, Kurzrock R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther. 2015;14(4):847–56.

    Article  CAS  Google Scholar 

  16. Darb-Esfahani S, Kunze CA, Kulbe H, Sehouli J, Wienert S, Lindner J, et al. Prognostic impact of programmed cell death-1 ( PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and and tumor-infiltrating lymphocytes in ovarian high grade serous carcinoma. Oncotarget. 2015;7(2):1486–99.

    Article  Google Scholar 

  17. Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csöszi T, Fülöp A, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375(19):1823–33.

    Article  CAS  Google Scholar 

  18. Eb G, Na R. This trial protocol has been provided by the authors to give readers additional information about their work. Protocol for: Garon EB, Rizvi NA, Hui R et al Pembrolizumab for the treatment of non–small-cell lung cancer. N Engl J Med. 2018. https://doi.org/10.1056/NEJMoa1.

  19. Karim R, Jordanova ES, Piersma SJ, Kenter GG, Chen L, Boer JM, 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):6341–7.

    Article  CAS  Google Scholar 

  20. Enwere EK, Kornaga EN, Dean M, Koulis TA, Phan T, Kalantarian 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):577–86.

    Article  CAS  Google Scholar 

  21. Heeren AM, Punt S, Bleeker MC, Gaarenstroom KN, Van Der Velden J, Kenter GG, et al. Prognostic effect of different PD-L1 expression patterns in squamous cell carcinoma and adenocarcinoma of the cervix. Mod Pathol. 2016;29(7):753–63.

    Article  CAS  Google Scholar 

  22. Heeren AM, de Boer E, Bleeker MCG, Musters RJP, Buist MR, Kenter GG, et al. Nodal metastasis in cervical cancer occurs in clearly delineated fields of immune suppression in the pelvic lymph catchment area. Oncotarget. 2015;6(32):32484–93.

    Article  Google Scholar 

  23. Gu X, Dong M, Liu Z, Mi Y, Yang J, Zhang Z, et al. Elevated PD-L1 expression predicts poor survival outcomes in patients with cervical cancer. Cancer Cell Int. 2019;19(1):1–9.

    Article  Google Scholar 

  24. Wu P, Wu D, Li L, Chai Y, Huang J. PD-L1 and survival in solid tumors: a meta-analysis. PLoS ONE. 2015;10(6):1–15.

    Google Scholar 

  25. He J, Zhang Y, Kang S, Shen J, He J, Jiang L, et al. Prognostic significance of programmed cell death 1 (PD-1) or PD-1 ligand 1 (PD-L1) expression in epithelial-originated cancer: a meta-analysis. Medicine. 2015;94(6):e515.

    Article  Google Scholar 

Download references

Acknowledgements

Acknowledgements of research support: Intramural funding from RCC, Thiruvananthapuram 695011, India.

Author information

Authors and Affiliations

  1. Gynec Oncology Clinic, Regional Cancer Centre, Thiruvananthapuram, Kerala, 695011, India

    Aryakrishna S. Lathika, Aswin Kumar, Susan Mathews, John Joseph & Francis V. James

  2. Cancer Research, Regional Cancer Centre, Thiruvananthapuram, Kerala, 695011, India

    S. Lakshmi

  3. Pathology, Regional Cancer Centre, Thiruvananthapuram, Kerala, 695011, India

    Preethi T. Ramdas

  4. Cancer Epidemiology and Biostatistics, Regional Cancer Centre, Thiruvananthapuram, Kerala, 695011, India

    Aleyamma Mathew

Authors
  1. Aryakrishna S. Lathika
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Lakshmi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Preethi T. Ramdas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aswin Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Susan Mathews
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. John Joseph
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Aleyamma Mathew
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Francis V. James
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Francis V. James.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lathika, A.S., Lakshmi, S., Ramdas, P.T. et al. Programmed Death Ligand 1 (PD-L1) Expression in Cervical Cancer. Indian J Gynecol Oncolog 19, 86 (2021). https://doi.org/10.1007/s40944-021-00584-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s40944-021-00584-y

Keywords

Search

Navigation