The Role of Liquid Biopsy in the Diagnosis of Oral Squamous Cell Carcinoma: A Systematic Review

TL;DR

This systematic review explores how liquid biopsy can help detect oral cancer early by analyzing bodily fluids like saliva and blood.

Contribution

The study systematically evaluates the potential of liquid biopsy as a complementary diagnostic tool for oral squamous cell carcinoma.

Findings

Tumor DNA and miRNA showed the highest diagnostic accuracy in liquid biopsy for OSCC.

Liquid biopsy can enable early detection in high-risk populations and monitor treatment response.

Most analyzed biomarkers demonstrated promising potential for future clinical use.

Abstract

Oral squamous cell carcinoma (OSCC) is one of the most prevalent types of cancer in the oral cavity and head and neck region. Due to its location and psychological and social implications, early detection and treatment are very important. A liquid biopsy can be used to diagnose cancer by analyzing samples of bodily fluids, such as saliva, blood, or urine, for specific molecules released by tumor cells. The objective of this study was to evaluate the use of liquid biopsy in the diagnosis of oral squamous cell carcinoma. A systematic review was carried out, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO: CRD420251238037). Articles taken into consideration for the review were published before 30 September 2025. The search for manuscripts for the review was conducted using PubMed, Scopus, Google Scholar, and Cochrane databases. Forty-three articles were deemed eligible for inclusion in the systematic review. Key data extracted from the studies included authorship, publication date, study location, methodology, number of participants, and reported complications. Most of the analyzed biomarkers showed promising potential for future use in liquid biopsy for OSCC diagnosis. Tumor DNA and miRNA demonstrated the highest diagnostic accuracy. The standard approach to diagnosis and planning treatment relies on tumor biopsy and diagnostic imaging. Liquid biopsy may complement this process by enabling early detection in high-risk populations and monitoring response to therapy. As such, it serves as a prognostic factor or therapeutic target, successfully identifying disease recurrence.

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