PROGNOSTIC SIGNIFICANCE OF P16 EXPRESSION ACROSS HISTOPATHOLOGICAL GRADES OF ORAL SQUAMOUS CELL CARCINOMA IN A TERTIARY CARE SETTING

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Dr Alamgir
Dr Faisal Pasha
Dr Ayesha Bibi
Dr Memoona Bibi
Dr Asad Mahmood
Ambreen Khurshid Haider

Keywords

Oral squamous cell carcinoma, P16, biomarker, cancer grade, survival analysis, immunohistochemistry, prognosis

Abstract

Background: Oral squamous cell carcinoma (OSCC) is a common head and neck cancer, accounting for 90% of oral malignancies. Despite treatment advances, survival rates are still low. P16, a key regulator of the cell cycle, has emerged as a potential biomarker in various cancers, including OSCC.


Objective: This study aimed to assess P16 expression across different OSCC grades and its value as a prognostic marker.


Methods: This observational study was conducted at different centers including Department of Oral Medicine, Women Dental College Abattabad and Ayub Medical College Abbottabad, Pakistan in the duration from November, 2023 to April, 2024. Sixty OSCC patients were categorized into well-differentiated, moderately differentiated, and poorly differentiated groups, with 20 patients each. P16 expression was evaluated using immunohistochemistry on tissue samples. Data analysis included descriptive statistics, Chi-square tests, and multivariate logistic regression to determine associations between P16, tumor grade, and clinical outcomes like survival and recurrence.


Results: P16 expression varied significantly with OSCC grade (p = 0.03). It was most prevalent in well-differentiated tumors (70%) and decreased in moderately (45%) and poorly differentiated tumors (20%). P16-positive patients showed longer survival (36.2 months) compared to P16-negative patients (28.9 months). Multivariate analysis confirmed P16 as a significant predictor of better survival (p = 0.01).


Conclusion: P16 correlates with OSCC grade and may serve as a useful prognostic marker. Incorporating P16 evaluation in routine OSCC diagnostics could improve patient stratification and treatment outcomes.

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References

1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. 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.
2. Sherr CJ, Roberts JM. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 1999;13(12):1501-12.
3. Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24-35.
4. Lewis JS Jr, Thorstad WL, Chernock RD, et al. p16 positive oropharyngeal squamous cell carcinoma: an entity with a favorable prognosis regardless of tumor HPV status. Am J Surg Pathol. 2010;34(8):1088-96.
5. Fakhry C, Andersen KK, Christensen J, Agrawal N, Eisele DW, Gillison ML. The impact of tonsillectomy upon the risk of oropharyngeal carcinoma diagnosis and prognosis in the Danish Cancer Registry. Cancer Prev Res (Phila). 2015;8(7):583-9.
6. Mirghani H, Amen F, Moreau F, Lacau St Guily J. Do high-risk human papillomaviruses cause oral cavity squamous cell carcinoma? Oral Oncol. 2015;51(3):229-36.
7. Bova R, Quinn DI, Nankervis JS, Cole IE, Sheridan M, Sutherland RL. Cyclin D1 and p16INK4A expression predict reduced survival in carcinoma of the anterior tongue. Clin Cancer Res. 1999;5(10):2810-9.
8. Hermsen MA, Baez A, Schuuring E, et al. Comparative genomic hybridization profiles of carcinomas from squamous cell carcinoma of the head and neck: accumulation of genetic alterations during tumor development. Am J Pathol. 2001;158(6):1945-51.
9. Hall M, Peters G. Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer. Adv Cancer Res. 1996;68:67-108.
10. Nakahara Y, Shintani S, Mihara M, et al. Alterations of Rb, p16, and cyclin D1 in oral squamous cell carcinoma: prognostic implications. Cancer. 2000;89(10):2096-107.
11. Murakami Y, Kato K, Ito S, et al. Predictive value of cyclin D1 and p16 expression in stage II and III esophageal squamous cell carcinoma patients undergoing chemoradiotherapy. Cancer Sci. 2007;98(7):1002-7.
12. Lassen P, Eriksen JG, Hamilton-Dutoit S, Tramm T, Alsner J, Overgaard J. Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck. J Clin Oncol. 2009;27(12):1992-8.
13. Weinberger PM, Yu Z, Haffty BG, et al. Molecular classification identifies a subset of human papillomavirus--associated oropharyngeal cancers with favorable prognosis. J Clin Oncol. 2006;24(5):736-47.
14. Gillison ML, Koch WM, Capone RB, et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000;92(9):709-20.