Salivary Biomarkers for the Early Detection and Prognostic Stratification of Oral Squamous Cell Carcinoma

Hafiz Waqas  Ahmed; Munazza  Kafait; Ayesha Rais; Zakia  Yaqoob; Bilal  Basit; Javeria Saleem

doi:10.36283/ziun-pjmd14-4/069

Authors

Hafiz Waqas Ahmed Mayo Hospital/ King Edward Medical University, Lahore, Pakistan.
Munazza Kafait Lahore Specialists Clinic, Lahore, Pakistan.
Ayesha Rais Sandeman Provincial Hospital ,Bolan University of Medical and Health Sciences (BUMHS) in Quetta, Balochistan.
Zakia Yaqoob Sandeman Provincial Hospital, Bolan University of Medical and Health Sciences (BUMHS) in Quetta, Balochistan.
Bilal Basit Rashid Latif Dental College , Lahore,Pakistan.
Javeria Saleem Green International University, Lahore, Pakistan.

DOI:

https://doi.org/10.36283/ziun-pjmd14-4/069

Keywords:

Oral squamous cell carcinoma, Salivary Biomarkers , EGFR, IL-8, miR-1246, Proteomics, Transcriptomics, ROC curve

Abstract

Introduction: Oral squamous cell carcinoma (OSCC) remains a major public health burden, especially in low- and middle-income countries. Traditional diagnostic modalities are often invasive and fail to detect early-stage disease. Saliva, as a non-invasive and readily accessible diagnostic fluid, has gained increasing attention for its potential to reflect molecular changes associated with malignancy. This study explores the diagnostic and prognostic utility of salivary biomarkers—spanning genomic, transcriptomic, proteomic, exosomal, and metabolomic classes—in patients with OSCC. To assess the diagnostic accuracy and predictive value of selected salivary biomarkers for OSCC using logistic regression analysis and stage-wise correlation.

Methods: This multicenter case-control study enrolled 400 participants: 200 confirmed OSCC cases, 120 patients with oral potentially malignant disorders (OPMDs), and 80 healthy controls. Unstimulated saliva samples were collected and analyzed using qPCR, ELISA, and mass spectrometry for key biomarkers including EGFR, p53, IL-8, Ki-67, miR-423-5p, miR-1246, CYFRA 21-1, SAT1, NUS1, sialic acid, and exosomal EGFR. Logistic regression analysis was used to evaluate associations between biomarker levels and OSCC risk, while ROC curves assessed diagnostic accuracy (AUC).

Results: Logistic regression revealed strong associations between elevated salivary levels of exosomal miR-1246 (OR=2.90, 95% CI: 2.10–3.75), IL-8 (OR=2.10, 95% CI: 1.55–2.80), EGFR (OR=2.45, 95% CI: 1.80–3.34), and miR-423-5p (OR=2.70, 95% CI: 1.95–3.50) with OSCC presence (p < 0.001). Exosomal markers demonstrated >90% diagnostic accuracy (AUC > 0.90), outperforming genomic and proteomic markers. Stage-wise analysis showed increasing expression trends for IL-8, Ki-67, and p53 from stage I to IV. Combined biomarker panels improved diagnostic prediction, with integrated models yielding AUCs > 0.95.

Conclusion: Salivary biomarkers—particularly from transcriptomic and exosomal categories—offer high diagnostic and prognostic value for OSCC. Logistic modeling supports their clinical use in non-invasive screening, especially in early-stage disease. This approach can significantly enhance early detection, reduce morbidity, and improve survival outcomes.

Author Biographies

Hafiz Waqas Ahmed, Mayo Hospital/ King Edward Medical University, Lahore, Pakistan.

Department of Oral and Maxillofacial Surgery and Registrar,
Munazza Kafait, Lahore Specialists Clinic, Lahore, Pakistan.

Department of Laser Dental Surgery,
Ayesha Rais, Sandeman Provincial Hospital ,Bolan University of Medical and Health Sciences (BUMHS) in Quetta, Balochistan.

Department of Oral & Maxillofacial Surgery,
Zakia Yaqoob, Sandeman Provincial Hospital, Bolan University of Medical and Health Sciences (BUMHS) in Quetta, Balochistan.

Department of Oral & Maxillofacial Surgery,
Bilal Basit, Rashid Latif Dental College , Lahore,Pakistan.

Department of Oral & Maxillofacial Surgery and Senior Registrar,

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