ASSOCIATION BETWEEN SALIVARY CYTOKINES AND HISTOPATHOLOGICAL GRADES OF ORAL EPITHELIAL DYSPLASIA
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Keywords
Oral epithelial dysplasia, Salivary cytokines, Non-invasive diagnosis.
Abstract
Background: : Oral epithelial dysplasia (OED) represents a critical precursor stage in the development of oral squamous cell carcinoma, making early detection essential. Salivary cytokines have emerged as promising non-invasive biomarkers due to their ability to reflect underlying inflammatory and molecular changes within dysplastic tissues.
Objective: To investigate the association between salivary cytokine levels and histopathological grades of oral epithelial dysplasia (OED), and to evaluate their potential role as non-invasive biomarkers for disease progression.
Methods: This cross-sectional analytical study included patients clinically suspected of having oral potentially malignant disorders. Unstimulated saliva samples were collected prior to biopsy and analyzed for key pro-inflammatory cytokines, including interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α), using enzyme-linked immunosorbent assay (ELISA). Histopathological grading of OED was performed according to WHO criteria and categorized into mild, moderate, and severe dysplasia. Cytokine concentrations were compared across dysplasia grades, and correlations were assessed using appropriate statistical tests.
Results: Mean salivary cytokine levels increased progressively with higher histopathological grades of OED. IL-6 and IL-8 showed a statistically significant association with dysplasia severity (p < 0.05), with the highest concentrations observed in severe dysplasia. TNF-α demonstrated a similar upward trend but did not reach statistical significance. Strong positive correlations were found between cytokine levels and histopathological grade, highlighting their potential role in reflecting epithelial alterations.
Conclusion: Elevated salivary cytokines, particularly IL-6 and IL-8, are significantly associated with higher grades of oral epithelial dysplasia. These findings support the potential utility of salivary cytokine profiling as a non-invasive adjunctive tool for early detection, risk stratification, and monitoring of OED progression. Further longitudinal studies are warranted to validate their predictive value in malignant transformation.
References
2. de Souza VG, de Lourdes Carvalho A, Miranda CS, Cardoso LP. Potential histopathological and immune biomarkers in malignant and non-malignant oral lesions. Journal of Oral & Maxillofacial Research. 2022 Dec 31;13(4):e3.
3. Miguel AF, Embaló B, Dias HB, Rivero ER. Immunohistochemical expression of MMP-9, TIMP-1, and vimentin and its correlation with inflammatory reaction and clinical parameters in oral epithelial dysplasia. Applied Immunohistochemistry & Molecular Morphology. 2021 May 1;29(5):382-9.
4. Tarek HE, Shalash HN, Morsy RA, Mostafa B, Hassan M, Abbas RM, Ellithy MM. Salivary and serum expression of TNF-α and Ki-67 in oral potentially malignant lesions. Bulletin of the National Research Centre. 2022 Sep 3;46(1):241.
5. Ferrari E, Pezzi ME, Cassi D, Pertinhez TA, Spisni A, Meleti M. Salivary cytokines as biomarkers for oral squamous cell carcinoma: a systematic review. International journal of molecular sciences. 2021 Jun 24;22(13):6795.
6. Diesch T, Filippi C, Fritschi N, Filippi A, Ritz N. Cytokines in saliva as biomarkers of oral and systemic oncological or infectious diseases: A systematic review. Cytokine. 2021 Jul 1;143:155506.
7. Manzano-Moreno FJ, Costela-Ruiz VJ, García-Recio E, Olmedo-Gaya MV, Ruiz C, Reyes-Botella C. Role of salivary MicroRNA and cytokines in the diagnosis and prognosis of oral squamous cell carcinoma. International journal of molecular sciences. 2021 Nov 11;22(22):12215.
8. Shahabinejad M, Zare R, Mohajertehran F, Mahdiraji AA. Cytokeratins (CK7 and CK20) genes expression association with clinicopathological indices in oral squamous cell carcinoma and dysplastic oral epithelium. Reports of biochemistry & molecular biology. 2021 Apr;10(1):126.
9. Piyarathne NS, Weerasekera MM, Fonseka PF, Karunatilleke AH, Liyanage RL, Jayasinghe RD, De Silva K, Yasawardene S, Gupta E, Jayasinghe JA, Abu-Eid R. Salivary interleukin levels in oral squamous cell carcinoma and oral epithelial dysplasia: findings from a Sri Lankan study. Cancers. 2023 Feb 28;15(5):1510.
10. Miguel AF, Poletto DA, Embaló B, Rivero ER. Association between epithelial-mesenchymal transition markers, proliferative index, and oral epithelial dysplasia: an immunohistochemical study. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology. 2023 Jun 1;135(6):904-13.
11. Benito-Ramal E, Egido-Moreno S, González-Navarro B, Jané-Salas E, Roselló-Llabrés X, López-López J. Role of selected salivary inflammatory cytokines in the diagnosis and prognosis of oral squamous cell carcinoma. A Systematic Review and Meta-analysis. Medicina Oral, Patologia Oral y Cirugia Bucal. 2023 Apr 26;28(5):e474.
12. Thomas A, Smitha T, Rao K, Priya NS, Sheethal HS, Chitra S. Expression of CD 20 B-Lymphocyte in oral epithelial dysplasia and oral squamous cell carcinoma: A comparative immunohistochemistry study. Journal of Oral and Maxillofacial Pathology. 2023 Apr 1;27(2):323-7.
13. Zdrojewski J, Nowak M, Nijakowski K, Jankowski J, Scribante A, Gallo S, Pascadopoli M, Surdacka A. Potential immunohistochemical biomarkers for grading oral dysplasia: a literature review. Biomedicines. 2024 Mar 5;12(3):577.
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All articles published in JPTCP are licensed under Copyright Creative Commons Attribution-NonCommercial 4.0 International License.
Bushra Khan
Lecturer Oral Biology, Khyber Medical University, Peshawar, Pakistan
Juveria Kulsoom
General Dentist, Rawalpindi, Pakistan
Amna Sharif
General Dentist, Islamabad, Pakistan
Fiza Shafiq
Assistant Professor Oral Pathology Department, Women Dental College, Abbottabad, Pakistan
Muhammad Arsalan Raffat
Associate Professor and Head of department Oral Pathology, Faculty of Dentistry, Shahida Islam Medical Complex, Lodhran, Pakistan
Tehmina Naushin
Associate Professor Oral Pathology, Peshawar Dental College, Riphah International University, Peshawar Campus, Pakistan
