Mutational Signatures May Define Oral Cancers

Researchers identified endogenous mutational and immune-response patterns in oral cancers arising without exposure to tobacco, alcohol, or human papillomavirus infections.

By
Andrea Surnit
May 26, 2026
3 min

MDSpire News

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

Cluster	Percentage of Tumors	Characteristics
SBS1	60%	Elevated clock-like endogenous mutagenesis
SBS1/APOBEC	34%	Increased APOBEC-related mutagenesis
SBS16	Varied	Observed primarily in smokers
SBS4/SBS92	Predominant in laryngeal tumors	Tobacco-associated signatures

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.