Introduction

Head and neck squamous cell carcinoma (HNSCC) comprises malignancies arising from the oral cavity, pharynx, larynx, nasal cavity, and salivary glands, and remains one of the most common cancers worldwide.1 Oral squamous cell carcinoma (OSCC) accounts for approximately 90% of oral malignancies and continues to represent a major public health burden, particularly in South Asian countries, where tobacco use, areca nut consumption, and alcohol are prevalent risk factors.2 Despite advances in surgery, radiotherapy, chemotherapy, and targeted therapies, the prognosis of OSCC remains poor because many patients present with advanced disease. Therefore, improving early detection and identifying reliable biomarkers remain major priorities in the field of oral cancer research.

Most OSCCs develop through a multistep process involving oral potentially malignant disorders (OPMDs). According to the latest consensus report from the WHO Collaborating Center for Oral Cancer, OPMDs comprise a heterogeneous group of clinical disorders associated with an increased risk of oral cancer development. These include leukoplakia, erythroplakia, proliferative verrucous leukoplakia, oral submucous fibrosis, oral lichen planus, oral lichenoid lesions, chronic graft-versus-host disease, and selected inherited disorders.2 Although only a proportion of these lesions progress to malignancy, early recognition and appropriate risk stratification remain fundamental for preventing progression to invasive carcinomas.

Among OPMDs, oral leukoplakia is the most frequently encountered lesion and carries a variable but clinically significant risk of malignant transformation. Histopathological assessment of oral epithelial dysplasia (OED) remains the gold standard for estimating this risk.3 However, dysplasia grading is limited by inter-observer variability, biological heterogeneity, and the inability to accurately predict malignant progression in every individual lesion. Consequently, there is a growing interest in identifying objective molecular biomarkers that can complement conventional histopathological evaluation and improve risk prediction.3,4

Recent studies have identified several molecular biomarkers with potential utility in predicting malignant transformation in oral potentially malignant disorders, further supporting the need for reliable biomarkers to improve risk stratification and early detection.5,6 Saliva has emerged as an attractive diagnostic biofluid because it can be collected non-invasively, repeatedly, and economically, while reflecting both local and systemic molecular alterations. Numerous salivary biomarkers, including proteins, messenger RNA, microRNA, DNA methylation markers, metabolites, extracellular vesicles, and inflammatory mediators, have been investigated for their role in the early detection of oral cancer.7 However, despite encouraging preliminary findings, no salivary biomarker has demonstrated sufficient diagnostic accuracy or reproducibility for routine clinical application, highlighting the need to identify reliable biomarkers for early disease detection and risk stratification.8,9

Telomeres are repetitive TTAGGG nucleotide sequences located at the ends of chromosomes that preserve chromosomal integrity and genomic stability during cell division.10,11 Progressive telomere shortening occurs with cellular aging and repeated replication, eventually leading to cellular senescence or apoptosis. Conversely, dysregulation of telomere maintenance via telomerase activation contributes to chromosomal instability, unlimited cellular proliferation, and carcinogenesis. Altered telomere length has been associated with several human malignancies, including oral cancer, suggesting that telomere biology may represent a useful indicator of early molecular alterations during carcinogenesis.12,13

Although telomere length has been extensively investigated in peripheral blood and tissue specimens, evidence regarding salivary telomere length in oral leukoplakia and OSCC remains limited. Considering the advantages of saliva as a liquid biopsy and the potential role of telomere shortening as an indicator of genomic instability, evaluating salivary telomere length may provide valuable insights into the early molecular alterations associated with oral carcinogenesis. Therefore, this preliminary case–control study aimed to evaluate salivary telomere length in healthy individuals, patients with oral leukoplakia, and patients with OSCC and investigate its potential as a non-invasive exploratory biomarker associated with early molecular changes during oral carcinogenesis.