Oral Squamous Cell Carcinoma Risk and Magnitude of Association in Inherited Cancer Predisposition Syndromes: Evidence from a Large Real-World Cohort

Document Type

Article

Publication Title

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

Abstract

Objective

Inherited cancer predisposition syndromes (ICPS) are rare genetic disorders associated with elevated cancer risk. This study evaluates oral squamous cell carcinoma (OSCC) prevalence across selected ICPS (Fanconi anemia (FA), Plummer–Vinson syndrome (PVS), Cowden syndrome (CS), Li–Fraumeni syndrome (LFS), Dyskeratosis congenita (DC), and Xeroderma pigmentosum), quantifies risk magnitude, examines age at diagnosis, and assesses tobacco’s modifying effect on OSCC risk in these populations.

Study Design

We conducted a retrospective cohort study using the TriNetX Research Network, including patients with or without ICPS identified by ICD‑10 codes over a 20‑year period. OSCC cases were matched 1:1 by age and sex to controls. Analyses assessed prevalence, odds ratios, age at diagnosis, and the impact of tobacco use. Statistical significance was set at p < 0.05.

Result

The prevalence of OSCC amongst ICPS patients ranged from 0.11% - 4.66%, with the highest in patients with FA. Among ICPS, only FA showed a markedly increased OSCC risk (OR = 40.63, p < 0.01), while PVS and DC were inversely associated. ICPS patients developed OSCC at younger ages (p < 0.0001). Smoking increased OSCC risk within ICPS (OR = 1.47), whereas non‑smokers with ICPS had reduced risk (OR = 0.78).

Conclusion

FA is strongly associated with OSCC; OSCC also occur in LFS and CS. ICPS patients present with OSCC at a younger age, supporting targeted screening for high‑risk ICPS populations.

DOI

10.1016/j.oooo.2025.11.010

Publication Date

11-26-2025

Keywords

Fanconi Anemia, Plummer–Vinson Syndrome, Cowden Syndrome, Li–Fraumeni Syndrome, Dyskeratosis Congenita, Xeroderma Pigmentosum, Oral Cancer

ISSN

2212-4411

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