# Oral Dysplasias to Carcinomas: Multi-omics Study of Progression

> **NIH NIH U01** · GEORGETOWN UNIVERSITY · 2024 · $650,973

## Abstract

Abstract
Oral squamous cell carcinomas (OSCCs) account for 35-38% of head and neck SCC, the 6th most common
cancer worldwide, and have a disappointing 5-year survival rate of ~50%. Oral epithelial dysplasia (OED) are
precursors to OSCC, but many go undiagnosed. Studies of OED allow characterization of the aberrant
molecular changes that lead to cancer. Yet due to inconsistencies in standard care and a lack of sufficient
longitudinal data, few studies have examined the molecular characteristics that drive the transformation of
OED to OSCC across time in the same patients to identify features unique to recurrence with progression.
There are very few longitudinal studies of OED progression, and those that exist have little epidemiologic
characterization and lack data integration from multi-omics. Additionally, existing reports concentrate on a few
common candidate genes and/or are limited to a small sample size. We will use our uniquely detailed
longitudinal cohort of OED to integrate clinical, histopathologic, epidemiologic and multiple molecular
characteristics of OED lesions to identify those hallmarks of OED lesions that lead to OSCC. This will benefit
patients by leading to improved risk prediction, more effective preventive measures, and insight into OSCC
biomarkers that indicate carcinogenesis. Use of a large, highly-characterized longitudinal cohort for this type of
multi-omics study, while using a second, independent population to validate generalizability, is highly
innovative. Viewed in light of the molecular profiles of OSCCs identified from our current set of tumors and
from TCGA HNSC data, this study will enable us to focus on the most relevant, recurrent changes, and
understand how OSCCs that proceed OED fit into the heterogeneity of overall OSCCs. Identification of
biomarkers predictive of progression will enable clinicians to provide more targeted preventive measures, and
vary the extensiveness of surgery and frequency of monitoring to increase quality of life.
 In Aim 1, we will use existing samples identify genomic, transcriptomic, and epigenetic profile
signatures distinguishing progressors from non-progressors at diagnosis for each OED stage. Our approach
allows us to identify a set of candidate biomarkers that distinguish high from low risk lesions, accounting for
important biologic variables. The goal of Aim 2 is to chart the timing of key genomic, transcriptomic, and
epigenetic changes associated with progression to OSCC, using extensive longitudinal cases, and comparing
observed changes to genes and pathways known to be aberrant in OSCC. In Aim 3, we will validate the
characterization of our unique longitudinal clinical cohort in OED with and without a subsequent diagnosis of
OSCC from the University of Michigan to identify clinicopathologic and epidemiologic predictors of recurrence
with progression.

## Key facts

- **NIH application ID:** 10915559
- **Project number:** 5U01DE033348-02
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** LAURA ROZEK
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $650,973
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10915559

## Citation

> US National Institutes of Health, RePORTER application 10915559, Oral Dysplasias to Carcinomas: Multi-omics Study of Progression (5U01DE033348-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10915559. Licensed CC0.

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