Advancing risk stratification for oral cancer prevention: Immune-based and molecular biomarkers in oral potentially malignant disorders across Europe

Description

Abstract- Background: Oral potentially malignant disorders (OPMD), including oral leukoplakia, erythroplakia, and erythroleukoplakia, affect an estimated 4–5% of the global population and account for a substantial proportion of oral squamous cell carcinomas (OSCC) arising through malignant transformation. To date, dysplasia is routinely classified by grade which is not a reliable predictor of outcomes, because it is a subjective assessment, very much related to pathologists training and experience. Improving early risk assessment in OPMD is a key unmet need in OSCC prevention, particularly in view of marked geographic heterogeneity in incidence, clinical practices, and access to specialized care across Europe. Objectives: The ISEBIO study (Immune-based Stratification and Evolutionary Biomarkers in OPMD) aims to improve oral cancer prevention by identifying immune-based and molecular biomarkers able to improve malignant transformation risk assessment beyond conventional histopathology. The primary objective is to identify biological features associated with progression from OPMD to OSCC. Secondary objectives include characterizing the molecular and immunological heterogeneity of OPMD and promote informed prevention strategies applicable across diverse European healthcare settings. Methods: ISEBIO is a retrospective, multicentric, pan-European study conducted within the INTERCEPTOR (Interception of oral cancer) COST Action (CA21140). Adult patients diagnosed with oral leukoplakia, erythroplakia, or erythroleukoplakia are included based on the availability of formalin-fixed paraffin-embedded (FFPE) tissue and adequate longitudinal follow-up, enabling classification as progressors or non progressors. All samples undergo centralized processing, quality control and pathological assessment by an international group of expert pathologists within the newly implemented OPMD Board developed within the INTERCEPTOR framework. This international virtual board enables harmonized reassessment of OPMD cases and contributes to a consensus-based evaluation of dysplasia patterns across participating countries (see Senada Koljenovic et al. abstract). Analyses include standardized histopathological review, CK13/CK17 immunohistochemistry, RNA sequencing using a 3’ Tag-Seq approach, and targeted DNA sequencing combining a whole-genome backbone and a head and neck cancer driver gene panel. The planned cohort size is approximately 246 patients, with an expected progressor-to non-progressor ratio of 1:3.
Results: As of early 2026, 11 clinical sites in 7 European countries and affiliated regions are actively contributing in providing clinical data and biological materials. Additional centers from 5 further countries are currently in the process of activation. Expert pathological review is undergoing through the international OPMD Board. To date, 157 cases have successfully passed quality control, with 65 additional cases currently being qualified. Recruitment is ongoing to ensure adequate representation of progressing lesions and balanced geographic coverage.
Conclusions: ISEBIO constitutes a major collaborative effort to advance biomarker driven oral cancer prevention in Europe. By integrating pathological features, immune, transcriptomic, and genomic data within a harmonized data model, the study aims to support evidence-based risk stratification for patients with OPMD. Beyond its scientific objectives, ISEBIO represents an important step toward pan
ABSTRACT SUBMISSION  European harmonization of data generation, interpretation, and sharing for OPMD, contributing to more consistent prevention strategies and reduced disparities in oral cancer outcomes.
Funded by INTERCEPTOR COST Action CA21140.

Period	19 May 2026 → 21 May 2026
Event title	IARC@60 Conference – Cancer Research into Action
Event type	Conference
Location	FranceShow on map
Degree of Recognition	International