Tehran University of Medical Sciences Journal of Craniomaxillofacial Research 2345-5489 12 4 2026 02 09 231 240 Elaheh Bahreini School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran. Nazanin Mahdavi Department of Oral and Maxillofacial Pathology, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran. Monir Moradzadeh Khiavi Department of Oral and Maxillofacial Pathology, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran. Abdolreza Mohamadnia Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Mahta Malek Craniomaxillofacial Research Center, Tehran University of Medical Sciences, Tehran, Iran. Naghmeh Bahrami Craniomaxillofacial Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. 2025 12 29 2026 01 04 Introduction: Oral lichen planus (OLP) and oral lichenoid lesions (OLL/OLR) are chronic inflammatory disorders of the oral mucosa with potential malignant transformation. Cytokeratins 6 and 16 (CK6, CK16) are markers of epithelial proliferation and have previously been reported to be elevated in inflammation, wound healing, and epithelial tumors. This study aimed to compare CK6 and CK16 mRNA expression across reticular OLP (ROLP), erosive OLP (EOLP), oral lichenoid lesions with dysplasia (OLR + D), oral squamous cell carcinoma (OSCC), and healthy controls.  Materials and Methods: A cross-sectional study was performed on 90 archived oral tissue specimens. mRNA expression was quantified using qRT-PCR, and data were analyzed using ΔCt, ΔΔCt, and fold-change values. Statistical comparisons were made using one-sample t-tests and one-way ANOVA.  Results: CK6 and CK16 expression were significantly altered in all lesion groups compared with controls (p < 0.001). Fold‑change analysis showed a slight decrease in CK6 expression in ROLP (0.63‑fold), followed by progressive increases in EOLP (1.59‑fold), OLR + D (1.85‑fold), and OSCC (2.33‑fold). CK16 expression increased from ROLP (1.36‑fold), EOLP (1.47‑fold), and OLR + D (2.00‑fold) to OSCC (2.72‑fold). However, no statistically significant differences were observed among the lesion groups for either gene (CK6: p = 0.840; CK16: p = 0.946). Conclusion: CK6 and CK16 expression increases along the spectrum of oral epithelial lesions but does not reliably distinguish inflammatory, dysplastic, and malignant lesions. These cytokeratins primarily reflect generalized inflammatory and reparative processes, and their interpretation should be integrated with histopathology, clinical findings, and additional molecular markers.  Keywords: Lichen planus; Oral lichenoid lesions; Oral squamous cell carcinoma; Epithelial dysplasia; Cytokeratin. https://jcr.tums.ac.ir/index.php/jcr/article/view/610 https://jcr.tums.ac.ir/index.php/jcr/article/download/610/466