Deciphering the Genomic Landscape of Oropharyngeal Squamous Cell Carcinoma: Distinct Mutation Patterns in Disease

Saturday, October 11, 2025

10:12 AM - 10:18 AM EDT

Location: 127

Disclosure(s):

Beau E. Hsia, BS:

faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Amanda Joy Bastien, MD:

faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Vijay A. Patel, MD:

faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Introduction: Oropharyngeal squamous cell carcinoma (OPSCC) is a subset of head and neck malignancies with two main etiologies: HPV-related (often p16-positive) or linked to tobacco/alcohol. Despite these differing risk factors, treatment-resistant and metastatic disease remain challenging. This study characterized the somatic mutational landscape of OPSCC to identify drivers of tumor progression and resistance.

Methods: Genomic data for 401 OPSCC patients (412 samples) from the AACR GENIE® database were analyzed for mutation prevalence, co-occurrence, and mutual exclusivity. Demographic, clinical, and tumor characteristics (e.g., primary vs. metastatic status) were assessed. Statistical analyses included chi-squared and t-tests with false-discovery rate corrections.

Results: Of 401 patients (412 samples), 399 (99.5%) were adults, 1 (0.25%) was pediatric, and 1 (0.25%) had unknown age. The cohort included 338 males (84.3%) and 63 females (15.7%). Comparisons of mutation prevalence revealed that TSC1 and TGFBR2 were nearly exclusive to primary tumors (p < 0.05), while CBLB, BUB1B, EIF4A2, RAD54B, and PIK3CB appeared only in metastatic samples (p < 0.05). Mutations in MET, TP53, and TRAF3 were enriched in females (p < 0.05), conversely, ZNF750 and FGA mutations were more frequently detected in male samples (p < 0.05), suggesting a possible sex-related predisposition.

Conclusions: Our findings underscore distinct mutation profiles between primary and metastatic OPSCC samples, highlighting the potential for co-occurring genetic alterations that may persist throughout tumor progression. Identifying mutations shared by both primary and distant lesions could clarify synergistic pathways driving metastasis. Clinically, this knowledge is especially relevant for HPV-mediated OPSCC, where treatment de-escalation strategies are under consideration. Patients harboring high-risk genetic alterations may be less suitable for reduced-intensity regimens, underscoring the need for personalized, mutation-informed therapeutic decisions.

Presenting Author(s)

SA

Saif Alshaka, BS

Creighton University School of Medicine
Phoenix, Arizona, United States

Disclosure information not submitted.

Senior Author(s)

SA

Saif Alshaka, BS

Creighton University School of Medicine
Phoenix, Arizona, United States

Disclosure information not submitted.

Co-Author(s)

Pedro S. Bonilla, MSc

Medical Student
Michigan State University College of Human Medicine
Los Angeles, California, United States

Disclosure information not submitted.
Vinay D. Veluvolu, n/a

Medical Student
N/A
Urbana, IL, United States

Disclosure information not submitted.
Nathan Tran, BS

Medical Student
Texas Tech University Health Sciences Center School of Medicine
Houston, Texas, United States

Disclosure information not submitted.
Gabriel A. Bitar, B.S.

Medical Student
Creighton university School of Medicine
Phoenix, Arizona, United States

Disclosure information not submitted.
Beau E. Hsia, BS

Medical student
Creighton University School of Medicine
Phoenix, AZ, United States

Disclosure(s):
faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.
SR

Stephen Russell, MD

Naval Medical Center - San Diego, United States

Disclosure information not submitted.
Amanda Joy Bastien, MD

Resident Physician
Cedars-Sinai Medical Center Program
Los Angeles, CA, United States

Disclosure(s):
faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.
AK

Aliasgher Khaku, MD

James A Haley VA Medical Center, United States

Disclosure information not submitted.
SP

Sean P. Polster, MD

Assistant Professor of Neurological Surgery
University of Chicago
Chicago, IL, United States

Disclosure information not submitted.
VP

Vijay A. Patel, MD

Assistant Professor
Rady Children's Hospital / UCSD
San Diego, CA, United States

Disclosure(s):
faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.