Potential noninvasive biomarkers for the malignant transformation of oral leukoplakia: A systematic review and meta‐analysis

BACKGROUND: The rising cancer incidence in patients with oral leukoplakia (OL) highlights the importance of identifying potential biomarkers for high‐risk individuals and lesions because these biomarkers are useful in developing personalized management strategies for OL patients. This study systematically searched and analyzed the literature on potential saliva and serum biomarkers for OL malignant transformation. METHODS: PubMed and Scopus were searched for studies published up to April 2022. The primary outcome of this study was the difference in biomarker concentrations in saliva or serum samples from healthy control (HC), OL and oral cancer (OC) populations. Cohen's d with 95% credible interval was calculated and pooled using the inverse variance heterogeneity method. RESULTS: A total of seven saliva biomarkers were analyzed in this paper, including interleukin‐1alpha, interleukin‐6 (IL‐6), interleukin‐6‐8, tumor necrosis factor alpha (TNF‐α), copper, zinc, and lactate dehydrogenase. IL‐6 and TNF‐α exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC. A total of 13 serum biomarkers were analyzed, including IL‐6, TNF‐α, C‐reactive protein, total cholesterol, triglycerides, high‐density lipoproteins, low‐density lipoproteins, albumin, protein, β2‐microglobulin, fucose, lipid‐bound sialic acid (LSA), and total sialic acid (TSA). LSA and TSA exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC. CONCLUSION: IL‐6 and TNF‐α in saliva have strong predictive values for OL deterioration, and LSA and TSA concentration levels in serum also have the potential to serve as biomarkers for OL deterioration.