p53 and Ki-67 as Biomarkers of Tumor Behavior in Squamous Cell Carcinoma: A PRISMA-Based Systematic Review and Meta-Analysis

Background: Oral squamous cell carcinoma (OSCC) is observed to account for most of the malignancies in the oral cavity. This systematic review and meta-analysis aimed to assess whether p53 and Ki-67 expression form a prognostic marker in oral squamous cell carcinoma (OSCC), and its relationships to the lymph node metastasis (LNM) and tumor aggressiveness. Methodology: PubMed, Scopus, Web of Science, and Google Scholar were searched up to the month November 2025. The studies that were included were observational cohort and cross-sectional studies that assessed p53 or Ki-67 expression in immunohistochemistry (IHC) and provided extractable counts of high/low expression and LNM. Titles, abstracts, and full texts were screened by two reviewers, and disagreements were settled by a third reviewer. The risk of bias was also determined based on the Newcastle–Ottawa Scale (NOS) and the certainty of evidence was determined based on a GRADE methodology. Results: There was no statistically significant correlation between the p53 expression and LNM (OR = 6.56; 95% CI: 0.28-155.9; I2 = 89%), indicating that the heterogeneity was high. On the contrary, Ki-67 overexpression was much related to LNM (OR = 5.67; 95% CI: 2.22-14.51; I2 = 35%), and this effect was reported in all studies. The stability of the Ki-67 pooled estimate was validated by the sensitivity analysis, but the results of p53 were sensitive to the elimination of specific studies. Conclusion: Ki-67 overexpression can serve as a predictable prognostic biomarker of metastasis to the lymph node, and p53 outcomes are inconclusive due to the heterogeneity of the methodology.