Significance of p53 overexpression in the prediction of the malignant transformation risk of oral potentially malignant disorders: A systematic review and meta-analysis

Objectives: To evaluate the current evidence in relation to the predictive value of p53 overexpression as a biomarker of the malignant transformation risk in oral potentially malignant disorders (OPMD). Material and methods: We searched PubMed, Embase, Web of Science and Scopus for studies published before July-2021, not restricted by date or publication language, with longitudinal design and assessing p53 overexpression by immunohistochemistry. We evaluated the quality of primary-level studies using QUIPS tool. We carried out meta-analyses, examined inter-study heterogeneity through subgroup and meta-regression analyses, and performed sensitivity and small-study effects analyses to test the stability and reliability of results. Results: Twenty four studies (1,210 patients) met inclusion criteria. P53 overexpression was associated with a statistically significant about 2 fold risk (RR = 1.88, 95 %CI = 1.39-2.56, p < 0.001). Leukoplakia maintained this significant relationship after subgroup meta-analysis (p = 0.002). Regarding the immunohistochemical technique, better results were obtained by the subgroups using anti-p53 DO7 antibody (p = 0.001), at high concentration (dilution < 1: 100, p < 0.001), incubated for long periods (overnight, p = 0.02), and at low temperature (4 degrees C, p = 0.007). Furthermore, meta-regression analysis showed that the association between p53 overexpression and higher oral cancer risk was independent of the presence and/or severity of epithelial dysplasia (p > 0.05). Conclusion: Our systematic review and meta-analysis supports the assessment of p53 overexpression in the prediction of the malignant transformation risk of OPMD.

Automated summary

This study evaluated the evidence on the predictive value of p53 overexpression as a biomarker for malignant transformation risk in oral potentially malignant disorders (OPMD). The findings indicated a significant association between p53 overexpression and a 2-fold increased risk of malignant transformation in OPMD, particularly in cases of leukoplakia. The use of the DO7 antibody, high concentration, long-term incubation, and low temperature yielded better results in immunohistochemical analysis. Importantly, the association between p53 overexpression and oral cancer risk was independent of the presence and severity of epithelial dysplasia.