Genomic and Human Papillomavirus Profiling of an Oral Cancer Cohort Identifies TP53 as a Predictor of Overall Survival

Presentation: D055
Topic: Mucosal - HPV Negative
Type: Poster
Date: Wednesday, May 1, 2019 (1:00 PM - 7:00 PM) | Thursday, May 2, 2019 (9:00 AM - 7:00 PM)
Session: Wednesday, May 1, 2019 (1:00 PM - 7:00 PM) | Thursday, May 2, 2019 (9:00 AM - 7:00 PM)
Authors: Neil Mundi, MD1, Stephenie Prokopec2, Farhad Ghasemi, BSc1, Andrew Warner, MSc1, John Yoo, MD1, Kevin Fung, MD1, Danielle Macneil, MD1, David Palma, MD, PhD1, John W Barrett, PhD1, Anthony C Nichols, MD1
Institution(s): 1Western University, 2Ontario Institute for Cancer Research

Background: The genomic landscape of head and neck cancer has been reported through The Cancer Genome Atlas project, however further external validation of genomic markers of failure is required. Here we attempt to determine if high-risk human papillomavirus (HPV) or frequently mutated genes are correlated with survival in an oral cancer cohort.

Methods: One hundred and thirty-five patients were included in this investigation, all undergoing primary surgical resection for oral cavity squamous cell carcinoma. Patient demographic data along with data from final pathology was collected. Tumor tissue was analyzed using a custom sequencing panel to identify selected genetic mutations; and assessed for the four most common high-risk HPV types (HPV 16, 18, 33, 35) by qPCR. Univariate and multivariate analysis were used to examine for associations between patient outcomes and mutational and HPV status.

Results: Conventional risk factors such as nodal status and T stage were significant determinants of overall survival and disease-free survival. Mutations were identified in TP53 (65%), PIK3CA (10%), HRAS (5%) and the TERT promoter (48%). Mutations in TP53 were found to significantly predict poorer overall survival. High-risk HPV was identified in 7% of cases, however tumor HPV status was not significantly associated with survival.

Conclusions: The mutational landscape of our oral cavity cohort was consistent with the literature, with targetable PIK3CA mutations identified in 10% of cases. Mutations in TP53 were associated with poor patient survival, highlighting this gene as a potential biomarker of treatment outcome. Expanding our sample size and increasing the number of genes tested may identify further predictors of outcome to direct customized cancer care.