# Genetic Landscape of Oral Cavity Squamous Cell Carcinoma

**Authors:** Joseph Celidonio, Sree Chinta, John Sebastian de Armas, Dylan Roden

PMC · DOI: 10.1002/oto2.70194 · OTO Open · 2026-01-21

## TL;DR

This study explores how gene mutations in oral cancer relate to tumor features and patient outcomes, finding that TP53 mutations are linked to aggressive tumor traits but not worse survival.

## Contribution

The study identifies associations between TP53 mutations and high-risk tumor features in oral cavity squamous cell carcinoma.

## Key findings

- TP53 mutations are associated with extranodal extension and perineural invasion in oral cavity squamous cell carcinoma.
- High tumor mutational burden is rare in this cancer type.
- TP53 mutations do not correlate with worse overall or disease-free survival.

## Abstract

The association, if any, between gene mutations, pathologic features of squamous cell carcinoma of the head and neck, and patient prognosis is unknown. This study investigates the association between common gene mutations in oral cavity squamous cell carcinoma, pathologic features of malignancy, and patient survival.

Retrospective database review.

US hospitals.

The cBioPortal for Cancer Genomics database was queried for oral cavity squamous cell carcinoma patient data. Statistical analyses were conducted using IBM SPSS v29.

Of the 423 patients included, the majority were male (66.6%), white (89.3%), and current/former smokers (74.1%). Tumor protein p53 (TP53), titin (TTN), and FAT atypical cadherin 1 (FAT1) mutations were present in 72.3%, 31.2%, and 22.0% of patients, respectively. Mutant TP53 was associated with positive extranodal extension compared to wild‐type (WT) TP53 (31.0% vs 18.8%) (P = .038) and perineural invasion (59.4% vs 44.3%, P = .021). High tumor mutational burden was present in 5.4% of cases. Gene mutations were not associated with differences in median overall survival or disease‐free survival. Multivariable analysis revealed an association between mutant TP53 and the presence of extranodal extension (odds ratio [OR] 2.61, 95% CI 1.05‐6.52, P = .039) and perineural invasion (OR 2.14, 95% CI 1.04‐4.42, P = .039).

Mutant TP53 was associated with high‐risk pathologic features, including extranodal extension and perineural invasion, but not with inferior survival. A high tumor mutational burden (>10) is rare in oral cavity squamous cell carcinoma. Further research into the interplay between genetic mutations and patient outcomes is needed.

## Linked entities

- **Genes:** TP53 (tumor protein p53) [NCBI Gene 7157], TTN (titin) [NCBI Gene 7273], FAT1 (FAT atypical cadherin 1) [NCBI Gene 2195]
- **Diseases:** oral cavity squamous cell carcinoma (MONDO:0004958)

## Full-text entities

- **Genes:** TTN (titin) [NCBI Gene 7273] {aka CMD1G, CMH9, CMPD4, CMYO5, CMYP5, EOMFC}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, FAT1 (FAT atypical cadherin 1) [NCBI Gene 2195] {aka CDHF7, CDHR8, FAT, ME5, hFat1}
- **Diseases:** Cancer (MESH:D009369), Oral Cavity Squamous Cell Carcinoma (MESH:D000077195)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

50 references — full list in the complete paper: https://tomesphere.com/paper/PMC12821888/full.md

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Source: https://tomesphere.com/paper/PMC12821888