Clinical Report: Unique Mutational Signatures May Define Oral Cancers

Overview

This study identifies distinct mutational profiles in oral cavity squamous cell carcinomas (OCSCC) without traditional risk factors. Two primary subtypes were characterized, revealing differences in mutational processes and biological pathways compared to tobacco-associated cancers.

Background

Oral cavity squamous cell carcinoma (OCSCC) represents a significant health concern, particularly as cases arise in patients without traditional risk factors such as smoking or HPV infection. This study provides insights into the molecular characteristics of OCSCC in patients with no identified risk factors.

Data Highlights

Key Findings

• Patients with OCSCC without traditional risk factors exhibited distinct mutational profiles compared to tobacco-associated cancers.
• Two main clusters were identified: SBS1 (60% of tumors) and SBS1/APOBEC (34% of tumors) among those with no identified risk factors.
• Mutations affecting antigen-presentation and immune-response genes were enriched in the SBS1 and SBS1/APOBEC clusters.
• Oral tongue squamous cell carcinomas were primarily found in the SBS1 cluster, while floor-of-mouth tumors were more common in the SBS16 cluster.
• Genomic analyses revealed differences in biological pathways in the no-identified-risk-factor groups.

Clinical Implications

The identification of distinct mutational signatures in OCSCC without known risk factors may inform future diagnostic and therapeutic strategies. Understanding these molecular profiles could lead to more personalized treatment approaches for patients with these cancers.

Conclusion

This study reports the unique mutational landscape of OCSCC in patients without traditional risk factors.

Related Resources & Content

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2. The ASCO Post — Mutational Profile May Impact Treatment Decisions for Smokers With Human Papillomavirus–Positive Oropharyngeal Cancer
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9. NCCN Guidelines® Insights: Head and Neck Cancers, Version 2.2025
10. Mutational signature-based classification uncovers emerging oral cancer subtypes with distinct molecular patterns | International Journal of Oral Science