2015 Funded Project

CFDHRE Peer Reviewed Grant ~ Open Category

Project Title:

“Can Clinicopathological Features of Low-Grade Oral Dysplasia with High-Risk Molecular Patterns Predict Malignant Progression?”

Lead Principal Applicant

Denise M. Laronde, RDH, PhD;
Title: Assistant Professor
Organization: The University of British Columbia, Faculty of Dentistry
Address: Room 170, J.B. Macdonald Building, 2199 Wesbrook Mall, Vancouver, BC Canada V6T 1Z3

Principal Applicant:

Leigha D. Rock, RDH, BDSc, (MSc candidate)
Title: Graduate Student
Organization: The University of British Columbia, Faculty of Dentistry
Address: Room 170, J.B. Macdonald Building, 2199 Wesbrook Mall, Vancouver, BC Canada V6T 1Z3

Award

$10,000

Abstract:

Problem Statement: Oral cancer has a poor survival rate mainly due to late stage diagnosis. Early detection is vital to the improvement of this prognosis. Oral potentially malignant lesions (OPML) with evidence of dysplasia are at greatest risk of progressing to oral cancer. However, not all OPML will progress to cancer; predicting which low-grade dysplasia (LGD; mild/moderate dysplasia) are at risk of progression is challenging. The malignant transformation of OPML is thought to be driven by the accumulation of genetic damage over time, which may result in changes in lesion behaviour such as persistence, disappearance and progression. Finding markers to predict which LGD will progress has the potential to guide the management of these lesions and improve patient outcomes.

Purpose/Aim: 1) To identify the clinicopathological changes in toluidine blue (TB) uptake over time, in lesions with identified molecular risk patterns; 2) to determine if these changes predict malignant progression.

Methods: Inclusion criteria include a histologically confirmed LGD, no previous history of head and neck cancer, and a minimum of one year of follow-up. Molecular data (loss of heterozygosity at key chromosomal loci) will be at baseline. Comparative biopsies will be collected approximately every 24 months. Demographic and clinical data, including TB positivity are collected every six months. Outcome is progression to severe dysplasia, carcinoma in situ (CIS), or squamous cell carcinoma (SCC).

Results: We anticipate that there will be an interaction between high-risk molecular changes and temporal patterns of TB staining which will be associated with progression. We expect high-risk LGD which progress to outcome are more likely to have a history of TB positivity, repeated positivity, and returning positivity than those that do not progress.

Conclusions: Temporal patterns of clinicopathological changes in TB staining, during follow-up signal a change in risk, and may aid in clinician judgment regarding the need for further biopsy.