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Oral Squamous Cell Carcinoma With and Without a History of OPMDs: A Retrospective Study of Clinicopathological Characteristics
by
, , , , , and
Gianluca Tenore
,
Ahmed Mohsen
,
Gian Marco Podda
*,
Lucia Borghetti
,
Federica Rocchetti
, 
Laura Sansotta
,
Andrea Battisti
,
Valentino Valentini
,
Antonella Polimeni
and
Umberto Romeo
Department of Oral and Maxillofacial Sciences (SOMF), Sapienza University of Rome, 00161 Rome, Italy
*
Author to whom correspondence should be addressed.
Cancers 2026, 18(17), 2776; https://doi.org/10.3390/cancers18172776
Submission received: 12 July 2026
/
Revised: 25 August 2026
/
Accepted: 26 August 2026
/
Published: 26 August 2026
(This article belongs to the Special Issue Oral Potentially Malignant Disorders and Oral Cavity Cancer: 2nd Edition)
Simple Summary
A substantial proportion of oral squamous cell carcinomas develop without clinically detectable precursor lesions, making early diagnosis particularly challenging. Identifying differences between tumors arising from oral potentially malignant disorders and those developing apparently de novo may improve understanding of oral carcinogenesis and support more effective surveillance strategies. The aim of this retrospective study was to compare the clinical characteristics, risk factors, histopathological features, and diagnostic management of patients affected by oral squamous cell carcinoma with or without a history of precursor lesions. In a cohort of 77 patients, most tumors developed in the absence of recognized precursor lesions, while patients with oral potentially malignant disorders underwent more frequent biopsies and closer follow-up. These findings support the existence of heterogeneous carcinogenic pathways and highlight the need for careful clinical surveillance beyond patients with known precursor lesions.
Abstract
Background: Oral squamous cell carcinoma (OSCC) is a multifactorial malignancy traditionally associated with tobacco exposure, alcohol consumption, and human papillomavirus (HPV) infection. It may also arise through the malignant transformation of oral potentially malignant disorders (OPMDs). However, a substantial proportion of tumors arise without clinically detectable precursor lesions, suggesting heterogeneous carcinogenic pathways. This study aimed to compare the clinicopathological characteristics of OPMDs-associated and apparently de novo OSCC. Methods: A retrospective analysis was conducted on patients with histologically confirmed OSCC referred to the department between 2015 and 2025. Baseline patient characteristics, clinical, and histopathological diagnostic management data were collected from medical records, and patients were classified as the OSCC with OPMD group or the de novo OSCC group based on the presence or absence of a history of OPMDs. Results: Seventy-seven patients were included (mean age: 70.4 years; 53.2% males, 46.75% females). OPMDs were documented in 37.66% of cases, while 62.34% of tumors developed without documented precursor lesions. No significant difference was observed in histological grade distribution between the two groups (p = 0.206), although G1 tumors were more frequent in the OSCC with OPMD group (25.93%) than in the de novo OSCC group (9.30%). The de novo OSCC group showed a significantly higher prevalence of denture-related lesions. No significant differences were observed between the two considered groups in age, sex, tobacco or alcohol exposure, HPV status, systemic diseases, or oncological history. Patients with OPMDs underwent significantly more biopsies in total and biopsies per year. Conclusions: OSCC may develop through distinct pathogenic pathways, emphasizing the need for broader clinical vigilance beyond OPMD surveillance to improve early diagnosis.
