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Quantification of somatic copy-number alterations to predict malignant transformation of oral leukoplakia: A prospective cohort study

Oral Oncol. 2026 Aug 10;181:108102. doi: 10.1016/j.oraloncology.2026.108102. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to evaluate the predictive value of a quantitative index measuring the extent of somatic copy-number alteration (SCNA) for malignant transformation (MT) in oral leukoplakia (OLK).

METHODS: A prospective cohort of 122 patients with OLK was followed for a median of 74 months. Whole-exome sequencing (WES) was performed on fresh-frozen tissue specimens. SCNA-L was defined as the total autosomal length of segments exceeding predefined copy-number and minimum-width thresholds. The cohort was stratified into high- and low-SCNA-L groups using a median cutoff of 3.3. The primary outcome was MT to oral squamous cell carcinoma (OSCC). Statistical analyses included Kaplan-Meier survival analysis, Cox proportional hazards models, time-dependent ROC curves, a 1,000-resample bootstrap optimism-corrected C-index, and bootstrap internal validation using calibration curves.

RESULTS: The MT rate was significantly higher in the high-SCNA-L group (26.7%) than in the low-SCNA-L group (6.5%; P < 0.01). SCNA-L remained an independent predictor of MT in the multivariable analysis (hazard ratio = 4.684, P = 0.006). The predictive model, incorporating SCNA-L and lesion type, demonstrated adequate discrimination and satisfactory calibration for mid-term prediction.

CONCLUSIONS: As an independent predictor of MT in OLK, the quantitative index SCNA-L can serve as a molecular supplement to conventional pathological grading.

PMID:42574790 | DOI:10.1016/j.oraloncology.2026.108102

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