Programmed death-ligand 1 and p53 as a biomarker in predicting oropharyngeal squamous cell carcinoma

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Abstract

Introduction. Currently, the pathogenetic role of the human papillomavirus (HPV) in carcinogenesis is well studied, that most cases of oropharyngeal squamous cell carcinoma are associated with the persistence of this infection. In addition to HPV infection, the involvement of programmed death-ligand 1 (PD-L1) and p53 proteins in the initiation and progression of oropharyngeal squamous cell carcinoma provides their formation as additional biomarkers in predicting the disease.

Aim. To study the prognostic role of PD-L1 and p53 expression in oropharyngeal squamous cell carcinoma depending on HPV status.

Materials and methods. The study included 62 patients with oropharyngeal squamous cell carcinoma T1–4N0–3M0 (Tumor, Nodus and Metastasis, (TNM), 7th edition) treated in 2015–2020 at the Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology and in the Tashkent and Samarkand city branches. All patients underwent immunohistochemical analysis for the presence of p16INK4a, PD-L1 and p53 protein expression in formalin-fixed and paraffin-embedded tumor tissue samples.

Results. Based on the results of the assessment, it was found that positive HPV status, low and medium levels of PD-L1 expression and positive regulation of wild-type p53 are associated with favorable outcomes in patients with oropharyngeal squamous cell carcinoma. Negative HPV status, high and very high levels of PD-L1 expression, loss of wild type p53 function with upregulation of p53 mutant type leads to worse disease outcomes.

Conclusion. Thus, the assessment of the expression of the onco-suppressor protein p53 helps to determine the biology of cancer cells in patients with oropharyngeal squamous cell carcinoma and suggest sensitivity to ongoing therapy, and by studying the regulation of the PD-L1 protein, antitumor immune regulation can be suggested in these patients.

About the authors

D. Sh. Polatova

Tashkent State Dental Institute

ORCID iD: 0000-0001-8128-2553

103 Makhtumkuli St., Tashkent 100047

Uzbekistan

A. Yu. Madaminov

Tashkent State Dental Institute

ORCID iD: 0000-0003-0064-3746

103 Makhtumkuli St., Tashkent 100047

Uzbekistan

A. V. Savkin

Tashkent State Dental Institute

Author for correspondence.
Email: sasha_worker_113@mail.ru

Alexander V. Savkin.

103 Makhtumkuli St., Tashkent 100047

Uzbekistan

A. Zh. Kakhkharov

Tashkent State Dental Institute

103 Makhtumkuli St., Tashkent 100047

Uzbekistan

G. K. Botiralieva

LLC “Ipsum pathology”

1 Bogiston St., Tashkent 100058

Uzbekistan

A. A. Madaliev

Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology

383 Farobi St., Tashkent 100179

Uzbekistan

N. B. Yuldashkhodzhaeva

Tashkent State Dental Institute

103 Makhtumkuli St., Tashkent 100047

Uzbekistan

Sh. K. Khuzhaev

Tashkent State Dental Institute

103 Makhtumkuli St., Tashkent 100047

Uzbekistan

References

  1. Bray F., Ferlay J., Soerjomataram I. et al. 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. doi: 10.3322/caac.21492
  2. Serrano B., Brotons M., Bosch F.X., Bruni L. Epidemiology and burden of HPV-related disease. Best Pract Res Clin Obstet Gynaecol 2018;47:14–26. doi: 10.1016/j.bpobgyn.2017.08.006
  3. Khalid M.B., Ting P., Pai A. et al. Initial presentation of human papillomavirus-related head and neck cancer: a retrospective review. Laryngoscope 2019;129(4):877–82. doi: 10.1002/lary.27296
  4. Mudunov A.M. The human papilloma virus is a new etiologic factor in the development of cancer of the head and neck organs. Problems and prospects for their solution. Ehpidemiologiya i vaktsinoprofilaktika = Epidemiology and Vaccinal Prevention 2018;17(5):100–5. (In Russ.). doi: 10.31631/2073-3046-2018-17-5-100-105
  5. Carlander A.F., Jakobsen K.K., Bendtsen S.K. et al. Contemporary systematic review on repartition of HPV-positivity in oropharyngeal cancer worldwide. Viruses 2021;13(7):1326. doi: 10.3390/v13071326
  6. Global Cancer Observatory. Available at: https://gco.iarc.fr/.
  7. Stukan’ A.I., Chukhray O.Yu., Porkhanov V.A. et al. Human papillomavirus-associated oropharyngeal carcinoma: trends in epidemiology and methods for detecting the virus in tumors. Opukholi golovy i shei = Head and Neck Tumors 2018;8(3):77–83. (In Russ.). doi: 10.17650/2222-1468-2018-8-3-77-83
  8. Hong A.M., Ferguson P., Dodds T. et al. Significant association of PD-L1 expression with human papillomavirus positivity and its prognostic impact in oropharyngeal cancer. Oral Oncol 2019;92:33–9. doi: 10.1016/j.oraloncology.2019.03.012
  9. Zhou G., Liu Z., Myers J.N. TP53 mutations in head and neck squamous cell carcinoma and their impact on disease progression and treatment response. J Cell Biochem 2016;117(12):2682–92. doi: 10.1002/jcb.25592
  10. Sinha P., Karadaghy O.A., Doering M.M. et al. Survival for HPV-positive oropharyngeal squamous cell carcinoma with surgical versus non-surgical treatment approach: a systematic review and meta-analysis. Oral Oncol 2018;86:121–31. doi: 10.1016/j.oraloncology
  11. Lewis J.S., Beadle B., Bishop J.A. et al. Human papillomavirus testing in head and neck carcinomas: guideline from the College of American Pathologists. Arch Pathol Lab Med 2018;142(5):559–97. doi: 10.5858/arpa.2017-0286-CP
  12. Westrich J.A., Warren C.J., Pyeon D. Evasion of host immune defenses by human papillomavirus. Virus Res 2017;231:21–33. doi: 10.1016/j.virusres.2016.11.023
  13. Golrokh M.M., Taghizadeh M.D., Faghihloo E. The roles of programmed death ligand 1 in virus-associated cancers. Infect Genet Evol 2020;84:104368. doi: 10.1016/j.meegid.2020.104368
  14. Zamani M.R., Aslani S., Salmaninejad A. et al. PD-1/PD-L and autoimmunity: a growing relationship. Cell Immunol 2016;310:27–41. doi: 10.1016/j.cellimm.2016.09.009
  15. Han Y., Liu D., Li L. PD-1/PD-L1 pathway: current researches in cancer. Am J Cancer Res 2020;10(3):727–42.
  16. Philips G.K., Atkins M. Therapeutic uses of anti-PD-1 and anti-PD-L1 antibodies. Int Immunol 2015;27(1):39–46. doi: 10.1093/intimm/dxu095
  17. Nishimura H., Honjo T. PD-1: an inhibitory immunoreceptor involved in peripheral tolerance. Trends Immunol 2001;22(5):265–8. doi: 10.1016/s1471-4906(01)01888-9

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Copyright (c) 2023 Polatova D.S., Madaminov A.Y., Savkin A.V., Kakhkharov A.Z., Botiralieva G.K., Madaliev A.A., Yuldashkhodzhaeva N.B., Khuzhaev S.K.

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