Prognostic Impact of Genetic Mutations and HPV Viral Integration in Locally Advanced Head and Neck Squamous Cell Carcinoma Patients 公开
Brummel, Collin (Spring 2024)
Abstract
Background: Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer typically caused by repeated exposure to carcinogens such as alcohol or tobacco, or via infection by high-risk strains of human papillomavirus (HPV). Five-year overall survival (OS) is between 65%-95%. Locally advanced HNSCC is treated with a combination of surgery, chemotherapy, and radiation. While the treatment goal is curative, treatment profoundly impacts quality of life. Novel treatment approaches are needed to maximize curative potential while improving patient quality of life post-treatment.
Objective: This study validates whether variables previously reported to have prognostic significance in HNSCC, TP53 or NOTCH1 genomic alterations, impact survival outcomes in a cohort of HNSCC tumors. Additionally, this study investigates whether HPV viral load within a tumor affects 5-year OS within a subset of these patients.
Methods: A de-identified dataset containing clinical, demographic, genomic, and viral data on 250 patients treated at the University of Michigan between 2000-2022 was analyzed. The primary outcome of interest was 5-year (OS). Patients were stratified by variables of interest and survival analyses were performed via the Kaplan-Meier method. Survival distributions were compared using the Mantel-Cox log-rank test, with putative predictor variables for OS further analyzed via univariate Cox proportional hazards regression analysis.
Results: Patients with TP53 mutated tumors had significantly worse 5-year OS (29.5% vs 72.8%, p < 0.0001) compared to those with TP53 wildtype tumors. NOTCH1 and HPV viral read count did not have a significant effect on OS. Cox proportional hazards analysis of baseline differences between the TP53 mutated and wildtype cohorts failed to identify an alternative predictor of OS.
Conclusion: TP53 mutation status, but not NOTCH1 mutation status or HPV viral read count quartile, significantly impacted 5-year OS in 231 locally advanced HNSCC patients. NOTCH1 and HPV viral read count were not recapitulated. This cohort may be useful in further assessing 1) the prognostic relevance of NOTCH1 mutations and HPV viral read count in HNSCC and 2) identifying other biomarkers that could optimize existing treatment approaches for HNC to improve survival and quality of life outcomes for patients affected by this highly morbid cancer type.
Table of Contents
Chapter 1: Introduction
Chapter 2: Review of the HNSCC Literature
Chapter 3: Methodology
Chapter 4: Results
Chapter 5: Conclusions, Implications, and Recommendations
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