Oral Surg Oral Med Oral Pathol Oral Radiol. 2025 Nov 26:S2212-4403(25)01321-5. doi: 10.1016/j.oooo.2025.11.010. Online ahead of print.
ABSTRACT
OBJECTIVE: Inherited cancer predisposition syndromes (ICPS) are rare genetic disorders associated with an elevated cancer risk. This study evaluates oral squamous cell carcinoma (OSCC) prevalence across selected ICPS, including Fanconi anemia (FA), Plummer-Vinson syndrome, Cowden syndrome, Li-Fraumeni syndrome, dyskeratosis congenita, 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. The analyses assessed prevalence, odds ratios, age at diagnosis, and the impact of tobacco use. Statistical significance was set at P < .05.
RESULTS: The prevalence of OSCC among ICPS patients ranged from 0.11% to 4.66%, with the highest in patients with FA. Among ICPS, only FA showed a markedly increased OSCC risk (OR = 40.63, P < .01), while Plummer-Vinson syndrome and dyskeratosis congenita were inversely associated. Patients with ICPS developed OSCC at younger ages (P < .0001). Smoking increased OSCC risk within ICPS (OR = 1.47), whereas nonsmokers with ICPS had a reduced risk (OR = 0.78).
CONCLUSIONS: FA is strongly associated with OSCC; OSCC also occurs in Li-Fraumeni syndrome and Cowden syndrome. Patients with ICPS present with OSCC at a younger age, supporting targeted screening for high‑risk ICPS populations.
PMID:41478787 | DOI:10.1016/j.oooo.2025.11.010
