Oral squamous cell carcinoma (OSCC) remains a significant global health challenge, with an estimated 378,000 new cases in 2020, projected to rise to 535,000 cases by 2040 (World Health Organization, 2020). Early detection and timely intervention are critical to improving survival outcomes (Boyle et al., 2003).

Histopathological grading of oral epithelial dysplasia (OED) continues to be the clinical gold standard for assessing the risk of malignant transformation. Despite its widespread use, OED grading suffers from low reproducibility and poor inter- and intra-observer agreement (Speight et al., 2015, Warnakulasuriya et al., 2008). Nevertheless, its biological rationale is supported by molecular evidence showing that the transition from normal epithelium to OSCC involves the accumulation of genetic mutations and chromosomal instability, which often manifest histologically as dysplasia (Bergshoeff et al., 2014, Castagnola et al., 2011, Dionne et al., 2015, Fonseca-Silva et al., 2016, Makarev et al., 2017, Sequeira et al., 2020, Tang et al., 2004). However, malignant transformation can also occur in lesions that lack histological evidence of dysplasia (Warnakulasuriya & Ariyawardana, 2016), underscoring the need for deeper insights into dysplastic evolution.

One major gap in the literature is the lack of longitudinal studies that track the temporal appearance of individual architectural and cytological features of dysplasia during carcinogenesis. Most existing data are cross-sectional or retrospective, limiting the ability to resolve which features emerge earliest, persist, or predict transformation (Mahmood et al., 2022). Moreover, while alternative strategies such as DNA ploidy analysis and hybrid grading systems have been explored (Dominguete et al., 2023, Sperandio et al., 2013, Sperandio et al., 2022), their clinical uptake has been inconsistent.

In parallel to histopathology, clinical visualization tools have been proposed to aid in early detection. One such strategy is tissue autofluorescence, where excitation with violet light (∼ 400 nm) leads to fluorescence emission that is diminished in dysplastic or neoplastic tissue due to structural and metabolic alterations (Epstein et al., 2012, Lane et al., 2006, Svistun et al., 2004). Portable optical devices utilizing this principle have been developed to assist in the clinical evaluation of suspicious lesions (McNamara et al., 2012, Simonato et al., 2019), though their diagnostic utility remains debated.

The present study aimed to prospectively evaluate the appearance and progression of individual architectural and cytological OED features in a well-established murine model of oral carcinogenesis; and to assess the clinical utility of a violet LED autofluorescence device (405 ± 20 nm) for early detection of mucosal changes in sites undergoing carcinogenesis.