Prognostic biomarkers and their impact on treatment strategy selection for patients with advanced stages of oropharyngeal cancer
DOI:
https://doi.org/10.26641/2307-0404.2025.1.325236Ключові слова:
oncology, oropharyngeal cancer, squamous cell carcinoma, human papillomavirus status, immunohistochemical study, biomarkers, epidermal growth factor receptor, Cyclin D1, Ki-67, cyclin dependent kinase inhibitor 2a gene, prognosis, treatmentАнотація
The study of prognostic biomarkers is crucial for personalising and enhancing the effectiveness of oropharyngeal cancer treatment, as they help identify patients with aggressive disease progression and determine the optimal patient management strategy. Purpose: Analysis of the effectiveness of the use of biomarkers in the context of human papillomavirus status for predicting oncological events, functional outcomes to optimise treatment approaches for patients with advanced oropharyngeal cancer. The study examined the results of examination and treatment of 120 patients aged 37 to 80 years, of both sexes diagnosed with stage III-IV oropharyngeal cancer (T3-4N0-3M0-1). The clinical and morphological characteristics and the outcomes of histological and immunohistochemical analyses of biopsy and surgical samples were assessed. Human papillomavirus (HPV) status was determined using immunohistochemistry for the p16 oncoprotein. Statistical analysis was performed using R Commander (https://www.r-project.org/) and MedCalc Statistical Software trial version 22.030 (https://www.medcalc.org/), applying descriptive and analytical statistics, rank correlation, logistic regression, and receiver operating characteristic (ROC) analysis. In late stages of oropharyngeal cancer, increased expression of Cyclin D1 and epidermal growth factor receptor (EGFR) was significantly more common in HPV-negative cases compared to HPV-positive ones (p<0.05). HPV-negative tumours were associated with homozygous deletion cyclin dependent kinase inhibitor 2a gene (CDKN2A). The identification of biomarkers as prognostic criteria for different HPV statuses confirms their role in choosing a treatment strategy. Biomarkers like Ki-67 and homozygous deletion of CDKN2A were prognostic for metastasis, while Ki-67 and Cyclin D1 were linked to recurrence. EGFR showed the highest prognostic accuracy for predicting masticatory muscle trismus. Increased expression of Cyclin D1 and Ki-67 in late stages of oropharyngeal neoplasms correlated with combined treatment, increasing the odds by 4.42 times and 25%, respectively (p<0.05). Evaluation of biomarkers such as p16, EGFR, Cyclin D1, and Ki-67 provides essential information into disease prognosis and response to treatment, enabling risk stratification, tailored treatment planning, and the development of personalized strategies for managing advanced oropharyngeal cancer.
Посилання
Zumsteg ZS, Luu M, Rosenberg PS, Elrod JK, Bray F, Vaccarella S, et al. Global epidemiologic patterns of oropharyngeal cancer incidence trends. J Natl Cancer Inst. 2023 Dec 6;115(12):1544-54. doi: https://doi.org/10.1093/jnci/djad169
Barsouk A, Aluru JS, Rawla P, Saginala K, Barsouk A. Epidemiology, Risk Factors, and Prevention of Head and Neck Squamous Cell Carcinoma. Med Sci (Basel). 2023 Jun 13;11(2):42. doi: https://doi.org/10.3390/medsci11020042
Bray F, Laversanne M, Sung H, Ferlay J, Sie-gel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-63. doi: https://doi.org/10.3322/caac.21834
Huang J, Chan SC, Ko S, Lok V, Zhang L, Lin X, et al. Disease burden, risk factors, and trends of lip, oral cavity, pharyngeal cancers: A global analysis. Cancer Med. 2023 Sep;12(17):18153-64. doi: https://doi.org/10.1002/cam4.6391
Fonsêca TC, Jural LA, Marañón-Vásquez GA, Magno MB, Roza ALOC, Ferreira DMTP, et al. Global prevalence of human papillomavirus-related oral and oro¬pharyngeal squamous cell carcinomas: a systematic review and meta-analysis. Clin Oral Investig. 2023;28(1):62. doi: https://doi.org/10.1007/s00784-023-05425-0
Lingen MW, Abt E, Agrawal N, Chaturvedi AK, Cohen E, D'Souza G, et al. Evidence-based clinical prac-tice guideline for the evaluation of potentially malignant disorders in the oral cavity: A report of the American Dental Association. J Am Dent Assoc. 2017 Oct;148(10):712-727.e10. doi: https://doi.org/10.1016/j.adaj.2017.07.032
Fedorenko ZP, Goulak LO, Gorokh YL, Ryzhov AY, Soumkina OV. Cancer in Ukraine 2022-2023: Incidence, mortality, prevalence and other relevant statistics. Bull Nat Cancer Reg Ukr [Internet]. 2024 [cited 2024 Oct 17];25:62. Available from: http://ncru.inf.ua/publications/BULL_25/PDF_E/Bull_Eng_25.pdf
Massa ST, Chidambaram S, Luong P, Graboyes EM, Mazul AL. Quantifying Total and Out-of-Pocket Costs Associated With Head and Neck Cancer Survivorship. JAMA Otolaryngol Head Neck Surg. 2022 Dec 1;148(12):1111-9. doi: https://doi.org/10.1001/jamaoto.2022.3269
Awawdeh MA, Sasikumar R, Aboalela AA, Sid-deeqh S, Gopinathan PA, Sawair F, et al. Evaluation of Prognostic Significance of the Expression of p53, Сyclin D1, EGFR in Advanced Oral Squamous Cell Carcinoma after Chemoradiation – A Systematic Review. Applied Sciences. 2023;13(9):5292. doi: https://doi.org/10.3390/app13095292
Rakhmanov VV, Shponka IS. [Features of the expression of Сyclin D1 and oncoprotein p27 in oropha-ryngeal squamous cell carcinomas with different proli-ferative potential]. Morphologia. 2023;17(2):52-60. Ukrainian.
doi: https://doi.org/10.26641/1997-9665.2023.2.52-60
Shponka IS, Bondarenko OO, Kovtunenko OV, Rakhmanov VV. Deletion of Сyclin dependent kinase inhibitor 2a gene as a marker of oropharyngeal carcinomas non-associated with human papillomavirus and its prognostic value. Medicni perspektivi. 2024;29(2):56-61. doi: https://doi.org/10.26641/2307-0404.2024.2.307479
Çorbacıoğlu ŞK, Aksel G. Receiver operating characteristic curve analysis in diagnostic accuracy studies: A guide to interpreting the area under the curve value. Turk J Emerg Med. 2023 Oct 3;23(4):195-8. doi: https://doi.org/10.4103/tjem.tjem_182_23
Raj R, Thankappan K, Janakiram C, Iyer S, Mathew A. Etiopathogenesis of Trismus in Patients With Head and Neck Cancer: An Exploratory Literature Review. Craniomaxillofac Trauma Reconstr. 2020 Sep;13(3):219-25. doi: https://doi.org/10.1177/1943387520917518
Culié D, Lisan Q, Leroy C, Modesto A, Schiappa R, Chamorey E, et al. Oropharyngeal cancer: First relapse description and prognostic factor of salvage treatment according to p16 status, a GETTEC multicentric study. Eur J Cancer. 2021 Jan;143:168-77. doi: https://doi.org/10.1016/j.ejca.2020.10.034
Tariq N, Mirza T, Ansari M, Nazir S. Role of Human Papilloma Virus 16/18 In Laryngeal Carcinoma with Correlation to the Expression of Сyclin D1, p53, p16 and EGFR. Pak J Med Sci. 2023 Nov-Dec;39(6):1768-73. doi: https://doi.org/10.12669/pjms.39.6.8220
Eberly HW, Sciscent BY, Lorenz FJ, Rettig EM, Goyal N. Current and Emerging Diagnostic, Prognostic, and Predictive Biomarkers in Head and Neck Cancer. Biomedicines. 2024 Feb 10;12(2):415. doi: https://doi.org/10.3390/biomedicines12020415
Pekarek L, Garrido-Gil MJ, Sánchez-Cendra A, Cassinello J, Pekarek T, Fraile-Martinez O, et al. Emerging histological and serological biomarkers in oral squamous cell carcinoma: Applications in diagnosis, prognosis evaluation and personalized therapeutics (Review). Oncol Rep. 2023 Dec;50(6):213. doi: https://doi.org/10.3892/or.2023.8650
##submission.downloads##
Опубліковано
Як цитувати
Номер
Розділ
Ліцензія
Авторське право (c) 2025 Медичні перспективи

Ця робота ліцензується відповідно до Creative Commons Attribution 4.0 International License.
Submitting manuscript to the journal "Medicni perspektivi" the author(s) agree with transferring copyright from the author(s) to publisher (including photos, figures, tables, etc.) editor, reproducing materials of the manuscript in the journal, Internet, translation into other languages, export and import of the issue with the author’s article, spreading without limitation of their period of validity both on the territory of Ukraine and other countries. This and other mutual duties of the author and all co-authors separately and editorial board are secured by written agreement by special form to use the article, the sample of which is presented on the site.
Author signs a written agreement and sends it to Editorial Board simultaneously with submission of the manuscript.