What are the early biomarkers for oral cancer before it becomes invasive from a pathological perspective?

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Last updated: March 10, 2025View editorial policy

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From the Guidelines

Early biomarkers for oral cancer detection before invasive stages include protein biomarkers such as CSTB, NDRG1, LTA4H, PGK1, COL6A1, and ITGAV, which have been identified as good predictors of disease outcomes. From a pathology perspective, identification begins with careful examination of potentially malignant disorders like leukoplakia, erythroplakia, and oral submucous fibrosis. Histopathological assessment remains the gold standard, revealing cellular atypia, nuclear pleomorphism, and altered nuclear-cytoplasmic ratios. Molecular techniques have enhanced detection capabilities, with salivary biomarkers offering particular promise as non-invasive screening tools.

  • Key biomarkers include:
    • CSTB
    • NDRG1
    • LTA4H
    • PGK1
    • COL6A1
    • ITGAV These biomarkers were identified in a study published in Nature Protocols in 2021 1, which used proteomics and immunohistochemistry to analyze tissue samples from patients with oral cancer. The study found that the expression of these proteins alone or in combination is a good predictor of disease outcomes and could lead to potential diagnostic assays. Regular oral examinations by dental professionals, particularly for high-risk individuals (tobacco users, alcohol consumers), remain crucial for early detection, as these biomarkers are most valuable when incorporated into systematic screening protocols that can identify malignant transformation at its earliest stages.
  • The importance of early detection is highlighted by the fact that oral cancer has a high mortality rate if left untreated, and that treatment outcomes are significantly improved when the disease is detected at an early stage.
  • Therefore, the use of these biomarkers in combination with regular oral examinations and histopathological assessment can help to improve the early detection and treatment of oral cancer, ultimately reducing morbidity and mortality.

From the Research

Early Biomarkers for Oral Cancer

The early detection of oral cancer is crucial for improving survival rates and quality of life for patients. From a pathological perspective, several biomarkers have been identified as potential indicators of oral cancer before it becomes invasive. These include:

  • CCND1 from the tumor 2
  • Human papillomavirus, HSP70, and IL-17 from the peripheral blood 2
  • High density of CD45RO+ tumor-infiltrating lymphocytes 2
  • Salivary biomarkers such as CYFRA 21-1, CA 19-9, lactate dehydrogenase (LDH), total proteins, and amylase 3, 4

Salivary Biomarkers

Saliva has gained interest as an alternative biofluid for non-invasive diagnostics, and several salivary biomarkers have been proposed for oral cancer detection. These include:

  • CYFRA 21-1 3, 4
  • CA 19-9 3, 4
  • Lactate dehydrogenase (LDH) 3, 4
  • Total proteins 3, 4
  • Amylase 3, 4 These biomarkers can be detected using various sensing technologies, including biosensors and point-of-care devices 5, 3

Point-of-Care Detection

Point-of-care (POC) devices have emerged as non- or minimally invasive tools for the diagnosis of oral cancer at an early stage. Various POC platforms have been developed for the detection of oral cancer biomarkers, including optical imaging methods and cytological adjuncts 5. These devices have the potential to improve diagnostic accuracy and reduce patient discomfort, especially in resource-limited settings 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Recent progress of biomarkers in oral cancers.

Journal of the Chinese Medical Association : JCMA, 2021

Research

Role of salivary biomarkers in early detection of oral squamous cell carcinoma.

Indian journal of pathology & microbiology, 2017

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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