Noninvasive, Saliva-Based Assay for Screening and Surveillance of Patients with Oral Cavity Squamous Cell Carcinoma (OCSCC)
Abstract
This project addresses the fiscal year 2022 (FY22) Peer Reviewed Cancer Research Program (PRCRP) PRCRP Topic Area – Head and Neck Cancers. Scientific objective and rationale: Oral cavity squamous cell carcinoma (OCSCC) is the most common head and neck cancer worldwide. Finding OCSCC early, when it’s small and hasn t spread, allows for more successful treatment and increases patients’ survival. However, oral cancer (especially in early stages) can be clinically deceptive, leading to misdiagnosis and treatment delay. Visual and tactile examination (current methods used for OCSCC detection) may often fail to discriminate between noncancerous and malignant lesions, ultimately requiring tissue biopsy evaluation (cutting of the lesion for laboratory testing) to confirm diagnosis and initiate treatment. However, these procedures are invasive, costly, and depend on examiner experience. Given that about 10% of the U.S. population have some type of oral mucosal abnormality (many of which are not cancerous), there is a pressing need for a non-invasive, accessible, and cost-effective method for screening patients with suspicious oral lesions, allowing early OCSCC detection while sparing unnecessary biopsies for patients with benign oral disorders. As OCSCC grows, it accumulates mutations in genes known to play a role in cancer progression. Our group and others have reported that such mutations can be detected in saliva of patients with OCSCC. However, no saliva-based screening method for early detection of OCSCC are currently available. Recently we have developed a method based on the targeted sequencing technology specifically designed to detect OCSCC-associated mutations (tumor DNA) in saliva, and validated this assay using matched primary tumors and saliva specimens collected in India (a county with high incidence of OCSCC). While these findings provide the foundation for using this ultra-sensitive and cost-efficient assay in clinical settings, frequency of cancer-driving mutations may vary in patients from different ethnical backgrounds. Given the racially and genetically heterogeneous population of the U.S. Armed Forces, it is critical to further assess the performance of this assay in demographically and epidemiologically diverse patient’s cohort. Our proposal will leverage the unique geographic location of the University of Chicago to evaluate the true potential and limitations of this test across heterogeneous patient populations, as well as across diverse therapeutic approaches for treatment of OCSCC. In Aim 1, we will assess the potential of this assay for noninvasive screening of patients with suspicious oral lesions and ruling out cancer. For this Aim we have prepared three groups of oral rinse specimens: (i) 300 samples collected from untreated patients with OCSCC (representing ethnically heterogeneous patient population); (ii) 100 samples from patients with noncancerous oral lesions; and (iii) 100 samples from healthy volunteers. A well-validated, saliva-based cancer detection assay with optimal performance would represent a significant clinical advancement in cancer care by reducing mortality, while lowering the socio-economic burden of OCSCC. In Aim 2, we will evaluate the feasibility of using this saliva-based method to detect early recurrent disease after OCSCC diagnosis and treatment. There are 25,000 patients treated in the U.S. alone that require routine monitoring (follow-up visits and radiologic imaging for at least 5 years after diagnosis), to ensure that their cancer hasn’t returned. Our highly sensitive assay could be performed more frequently than imaging, allowing identification of early recurrence or residual disease noninvasively, leading to increased chances of a curative salvage treatment. For this Aim, longitudinal saliva samples are already being collected from 120 patients with OCSCC: at baseline and 3, 6, 9, and 12 months following completion of treatment. If high correl
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310614
Entities
People
- Evgeny Izumchenko
Organizations
- United States Army
- University of Chicago