Predictive Value of the Loss of pRb Expression in the Malignant Transformation Risk of Oral Potentially Malignant Disorders: A Systematic Review and Meta-Analysis López Ansio, María Ramos García, Pablo González Moles, Miguel Ángel PRb Retinoblastoma protein Oral potentially malignant disorder Oral leukoplakia Malignant transformation We would like to thank the research group CTS-392 (Plan Andaluz de Investigación, Junta de Andalucía, Spain). Supplementary Materials: The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/cancers17020329/s1, Table S1 Objective: The aim of this systematic review and meta-analysis was to qualitatively and quantitatively evaluate the current evidence on the significance of the loss of early stages of oral carcinogenesis in lesions diagnosed according to clinical and/or histopathological criteria and their evolution to oral cancer. Materials and Methods: We searched MEDLINE (through PubMed), Embase, Scopus and Web of Science for primary-level studies published before November 2024, designed as prospective or retrospective longitudinal cohorts, and not restricted by language or publication date. The risk of bias was critically assessed using the QUIPS tool. Meta-analyses, heterogeneity exploration, sensitivity and small-study effect analyses were conducted. Results: The inclusion criteria were met by six primary-level studies, which recruited 330 patients with OPMDs with follow-up data. The loss of pRb expression, assessed through immunohistochemistry, was significantly associated with a higher malignant transformation risk of OPMDs (RR = 1.92, 95%CI = 1.25–2.94, p = 0.003). The leukoplakia subgroup retained this significant association (p = 0.006), being the OPMD where the loss of pRb expression showed the best predictive value for malignant transformation (RR = 2.00, 95%CI = 1.22–3.29). Regarding the immunohistochemical technique and scoring methods, better performance and results were achieved by applying a cutoff point > 10% pRb-positive cells with nuclear staining (RR = 2.10, 95%CI = 1.30–3.38, 95%CI = 0.002). Conclussion: The present systematic review and meta-analysis supports that the loss of expression of the tumor suppressor pRb, assessed through immunohistochemistry, is a predictor of the malignant transformation risk of oral leukoplakias. Future studies are needed in other OPMDs following the recommendations provided based on current evidence gaps. 2025-02-24T08:07:39Z 2025-02-24T08:07:39Z 2024-01-20 journal article López-Ansio, M.; Ramos-García, P.; González-Moles, M.Á. Predictive Value of the Loss of pRb Expression in the Malignant Transformation Risk of Oral Potentially Malignant Disorders: A Systematic Review and Meta-Analysis. Cancers 2025, 17, 329. https://doi.org/10.3390/cancers17020329 https://hdl.handle.net/10481/102608 10.3390/cancers17020329 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional MDPI