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Introduction Oral squamous cell carcinoma (OSCC) is associated with substantial morbidity and mortality worldwide, and its prognosis is heavily dependent on early detection. Saliva represents a valuable diagnostic medium for oral cancer detection due to its direct contact with lesions, non-invasive collection and ability to reflect local and systemic molecular alterations. Zinc Finger Protein 510 (ZFP510), implicated in tumourigenic pathways in other malignancies, has not been extensively studied in salivary diagnostics.Research design and methods The present case–control study included patients with clinically suspicious oral lesions subsequently confirmed as OSCC (n=30) and healthy controls (n=15). Unstimulated whole saliva was collected under standardised conditions. ZFP510 concentrations were quantified using ELISA. Statistical analyses were performed and receiver operating characteristic (ROC) analysis was assessed for diagnostic performance.Results Salivary ZFP510 levels were significantly elevated in OSCC patients compared with healthy controls (p<0.05). A strong positive correlation was observed between ZFP510 concentration and histopathological grade, with poorly differentiated carcinomas demonstrating the highest values. Several demographic and habit-related variables showed significant associations with ZFP510 levels. Multivariate analysis confirmed ZFP510 as an independent predictor of OSCC. ROC analysis demonstrated 87.3% sensitivity and 83.1% specificity.Conclusion Saliva represents a valuable diagnostic medium for oral cancer detection. The significant upregulation of ZFP510 in OSCC and its clear association with tumour dedifferentiation highlight its promise as a non-invasive biomarker for early diagnosis and disease monitoring. Larger multicentre validation studies incorporating tissue-level correlation and multimarker diagnostic frameworks are warranted.