Kate Chatfield-Reed1, Shanying Gui1, Wendi Q O'Neill1, Theodoros N Teknos2, Quintin Pan3. 1. Seidman Cancer Center, University Hospitals, Cleveland, OH 44106, United States; Department of Otolaryngology-Head and Neck Surgery, University Hospitals Cleveland Medical Center, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, United States. 2. Seidman Cancer Center, University Hospitals, Cleveland, OH 44106, United States; Department of Otolaryngology-Head and Neck Surgery, University Hospitals Cleveland Medical Center, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, United States; Case Comprehensive Cancer Center, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, United States. 3. Seidman Cancer Center, University Hospitals, Cleveland, OH 44106, United States; Department of Otolaryngology-Head and Neck Surgery, University Hospitals Cleveland Medical Center, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, United States; Case Comprehensive Cancer Center, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, United States. Electronic address: Quintin.Pan@UHhospitals.org.
Abstract
OBJECTIVE: To determine the influence of high-risk HPV genotype on outcomes in HNSCC patients. MATERIALS AND METHODS: This is a retrospective analysis of The Cancer Genome Atlas HNSCC cohort. RESULTS: Using multivariate Cox regression analysis, we revealed that HPV33+ HNSCC patients have inferior overall survival compared to HPV16+ HNSCC patients independent of anatomical site (HR 3.59, 95% CI 1.58-8.12; p = 0.002). A host anti-viral immune response, apolipoprotein B mRNA editing enzyme, and catalytic polypeptide-like mutational signature, was under represented and, aneuploidy and 3p loss were more frequent in HPV33+ tumors. A deconvolution RNA-Seq algorithm to infer immune cell fractions revealed that CD8+ cytotoxic T-cell infiltration was reduced in HPV33+ compared to HPV16+ tumors (1.3% vs. 2.7%, p = 0.007). TGFB1, a negative modulator of T-cell infiltration and function, showed expression and pathway enrichment in HPV33+ tumors. CONCLUSIONS: Our work reveals that HPV genotype, in particular HPV33, has a powerful impact on HNSCC patient survival. We argue that p16 immunohistochemistry as a surrogate biomarker for HPV+ status will lead to sub-optimal risk stratification and advocate HPV genotype testing as standard of care.
OBJECTIVE: To determine the influence of high-risk HPV genotype on outcomes in HNSCC patients. MATERIALS AND METHODS: This is a retrospective analysis of The Cancer Genome Atlas HNSCC cohort. RESULTS: Using multivariate Cox regression analysis, we revealed that HPV33+ HNSCC patients have inferior overall survival compared to HPV16+ HNSCC patients independent of anatomical site (HR 3.59, 95% CI 1.58-8.12; p = 0.002). A host anti-viral immune response, apolipoprotein B mRNA editing enzyme, and catalytic polypeptide-like mutational signature, was under represented and, aneuploidy and 3p loss were more frequent in HPV33+ tumors. A deconvolution RNA-Seq algorithm to infer immune cell fractions revealed that CD8+ cytotoxic T-cell infiltration was reduced in HPV33+ compared to HPV16+ tumors (1.3% vs. 2.7%, p = 0.007). TGFB1, a negative modulator of T-cell infiltration and function, showed expression and pathway enrichment in HPV33+ tumors. CONCLUSIONS: Our work reveals that HPV genotype, in particular HPV33, has a powerful impact on HNSCC patient survival. We argue that p16 immunohistochemistry as a surrogate biomarker for HPV+ status will lead to sub-optimal risk stratification and advocate HPV genotype testing as standard of care.
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