# Somatic Mutations in Tissue and Saliva as Prognostic and Screening Biomarkers for Oral Premalignancy

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2023 · $386,028

## Abstract

ABSTRACT
Oral cavity squamous cell carcinoma (OCSCC) can be a lethal disease that is often preceded by premalignant
lesions, making it is an ideal disease for screening initiatives. However, current screening protocols/tests cannot
reliably differentiate between inflammatory and premalignant dysplastic lesions. Further, the histologic diagnosis
of dysplasia is an imperfect predictor of malignant transformation as only ~15% of premalignant oral lesions
progress to cancer. Our long-term goals are to establish molecular-based diagnostic tests for prognostication
and screening that are capable of identifying high-risk patients most likely to progress to oral cancer but would
greatly benefit from closer surveillance and less morbid curative intent procedures. Our central hypothesis is that
premalignant lesions contain identifiable genetic mutations that can be used for reliable biopsy prognostication
(tissue biopsies) and screening (saliva). We will identify dysplasia-specific mutations underlying the
pathogenesis of OCSCC. We will validate the mutations identified in a retrospective case-cohort study of
dysplastic oral tissues with known clinical outcomes to investigate their potential as tissue-based prognostic
biomarkers. We will conduct a case-cohort study using saliva samples from five existing longitudinal population-
based United States cohorts to determine whether driver somatic mutations can be identified in saliva prior to
the diagnosis of oral cancer. These studies are conceptually innovative and likely to result in state-of-the-art risk
stratification and screening. They would be the first to define the functional driver mutations of oral
premalignancy. They would also be the first to determine if mutations in driver genes can be detected in saliva
prior to oral cancer diagnosis, to define the time-course of mutation detection, and to test the predictive ability of
identifying high-risk individuals with somatic mutations. They are technically innovative, as they evaluate the
diagnostic accuracy of a novel non-invasive molecular salivary screening platform. This research will benefit
human health by improving our ability to identify high-risk premalignant oral lesions likely to progress to cancer,
thereby allowing for earlier and potentially more curative interventions with limited morbidity and mortality.

## Key facts

- **NIH application ID:** 10614548
- **Project number:** 5R01DE028674-04
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Nishant Agrawal
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $386,028
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10614548

## Citation

> US National Institutes of Health, RePORTER application 10614548, Somatic Mutations in Tissue and Saliva as Prognostic and Screening Biomarkers for Oral Premalignancy (5R01DE028674-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10614548. Licensed CC0.

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