Bridging Oral Pathology with Diagnostics by Comparative Analysis of Oral Fibrosis as a Precursor to Carcinogenesis: A Systematic Review and Meta-Analysis

Authors

  • Tayyaba Rafiq Medical and Dental College, Lahore, Pakistan.
  • Anum Usman Al Nafees Medical College and Hospital, Isra University Islamabad Campus, Islamabad Pakistan
  • Madeeha Minhas College of Science and Health Professions, King Saud bin Abdulaziz University for Health sciences, Jeddah, Saudi Arabia.
  • Sajid Ali Majeedano Muhammad Dental College, Mirpurkhas, Pakistan.
  • Aliya Zaman Muhammad Medical and Dental College, Mirpurkhas, Sindh,Pakistan.
  • Shahzaman Memon Muhammad Dental College, Ibn-e-Sina University, Mirpurkhas,Pakistan.

DOI:

https://doi.org/10.36283/ziun-pjmd14-3/072

Keywords:

Mouth Neoplasms, Oral Submucous Fibrosis, Cell Proliferation, Systematic Review, Meta-Analysis

Abstract

Background: Oral Submucous Fibrosis (OSF) is a chronic, potentially malignant condition that causes progressive fibrosis of the oral mucosa because people consume areca nuts. The purpose of this systematic review and meta-analysis was to compile the most recent data on molecular changes in OSF and assess how they relate to malignant transformation.

Methods: A PRISMA-guided thorough search of PubMed, Scopus, Web of Science, and Google Scholar was carried out through March 2025. Original studies assessing molecular or cellular alterations in OSF (with or without comparisons to oral squamous cell carcinoma (OSCC) or normal mucosa) were eligible. RevMan 5.4 was used to conduct the meta-analysis, and GRADE was used to evaluate the degree of evidence certainty, the Newcastle Ottawa tool, and the QUIN Tool for risk of bias.

Results: Eleven studies satisfied the requirements to be included. The main molecular changes were abnormal expression of p53 and Ki67, upregulation of hTERT, shifts in EMT markers, and dysregulation of TGF-β/SMAD signaling. The pooled effect sizes for EMT stemness -0.67 [-1.09, -0.25, I2 = 0%, p=0.0016], for proliferation 4.49 [1.68, 7.29, I2= 96.8%, p=0.0017], for telomerase activation -0.63 [-5.93, 4.68, I2 = 98.3%, p= 0.8172], for signaling pathway mediators -429.76 [-1289.16, 429.94, I2 = 98.2%, p = 0.3272]. The investigators assigned a moderate rating to evidence certainty.

Discussion: The molecular alterations in OSF are persistent and strongly suggest a risk of malignant cell transformation. Healthcare practitioners may be able to improve their early disease detection and risk level classification with the use of molecular biomarkers.

Author Biographies

  • Tayyaba Rafiq, Medical and Dental College, Lahore, Pakistan.

    Department of Oral and Maxillofacial Surgery, 

  • Anum Usman, Al Nafees Medical College and Hospital, Isra University Islamabad Campus, Islamabad Pakistan

    Department of Pathology, 

  • Madeeha Minhas, College of Science and Health Professions, King Saud bin Abdulaziz University for Health sciences, Jeddah, Saudi Arabia.

    Department of Basic Sciences-Pathology, 

  • Sajid Ali Majeedano, Muhammad Dental College, Mirpurkhas, Pakistan.

    Department of Oral Medicine,

  • Aliya Zaman, Muhammad Medical and Dental College, Mirpurkhas, Sindh,Pakistan.

    Department of Pathology,

  • Shahzaman Memon, Muhammad Dental College, Ibn-e-Sina University, Mirpurkhas,Pakistan.

    Department of Oral Pathology, 

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2025-07-21

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Rafiq T, Usman A, Minhas M, Majeedano SA, Zaman A, Memon S. Bridging Oral Pathology with Diagnostics by Comparative Analysis of Oral Fibrosis as a Precursor to Carcinogenesis: A Systematic Review and Meta-Analysis. PJMD [Internet]. 2025 Jul. 21 [cited 2026 Jun. 9];14(3):549-60. Available from: https://ojs.zu.edu.pk/pjmd/article/view/3689

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