Mutation frequency in 15 common cancer genes in high‐risk head and neck squamous cell carcinoma

Abstract

Background With prior studies having looked at unselected cohorts, we sought to explore the mutational landscape in a high-risk group of head and neck squamous cell carcinoma (HNSCC) tumors. Methods A multiplexed polymerase chain reaction (PCR) assay evaluating 68 loci in 15 genes was performed on 64 patients with high-risk HNSCC. Because of the frequent PIK3CA and AKT1 mutations in patients with oropharyngeal carcinoma, we evaluated the relationship between mutation status and both clinical/pathologic variables and tumor control in this subgroup. Results Seventeen of 64 patients harbored mutations in the assayed loci: 16% in PIK3CA, 9% in TP53, 2% in AKT1, and 2% in epidermal growth factor receptor (EGFR). The frequency of PIK3CA/AKT1 mutations in oropharyngeal and sinonasal primaries was increased compared to other primary sites (35% vs 6%; p = .005). There was no relationship between mutation status and overall survival (OS), disease-specific death, or progression in the oropharyngeal cohort. Conclusion We identified frequent PIK3CA mutations in patients with high-risk HNSCC confined predominantly to the oropharyngeal and sinonasal subsites; for the first time, mutation in AKT1 has been identified in HNSCC.

Identification of the Cell-Intrinsic and -Extrinsic Pathways Downstream of EGFR and IFNγ That Induce PD-L1 Expression in Head and Neck Cancer

“…Likewise, in the setting of NSCLC, PD-L1 protein was upregulated after EGFR/RAS/MAPK pathway activating mutations. Indeed, HRAS and EGFR mutations in NSCLC are far more frequent than in HNC (2–5%) (43, 44). Therefore, mutant EGFR may induce a stronger MAPK pathway activation than wild type EGFR.…”

“…Since EGFR mutations are very rare in HNC (2%) (43), EGFR pathway overactivation, rather than activating mutations, are more important for PD-L1 upregulation in HNC. We are the first to report that wild type EGFR pathway induces PD-L1 upregulation at the mRNA and protein level, and that specific JAK2 inhibition significantly downregulated baseline and EGF-induced PD-L1 upregulation, though not completely, suggesting that other alternative pathways also contribute to PD-L1 expression in HNC.…”

Mutation and Transcriptional Profiling of Formalin-Fixed Paraffin Embedded Specimens as Companion Methods to Immunohistochemistry for Determining Therapeutic Targets in Oropharyngeal Squamous Cell Carcinoma (OPSCC): A Pilot of Proof of Principle

“…However, these technologies have had little impact on standard methods for diagnosis and treatment of HNSCC and many other types of cancer with one or more known mutational or copy number drivers. Despite extensive literature of differential gene expression profiles, mutations and copy number abnormalities in head and neck tumors that could potentially impact future clinical applications, little other than HPV status is done routinely upon diagnosis [7,10,11,13,15,24,32,[35][36][37][38][39][40][41][42][43][44][45][46][47]. A main factor contributing to this lack of progress is that no clear directives or actionable guidelines have been adopted for molecularly profiling HNSCCs.…”

The PI3K/Akt/mTOR axis in head and neck cancer: functions, aberrations, cross‐talk, and therapies

“…When considering the importance of human papilloma virus (HPV) oncoproteins E6 and E7 in the etiology of a subset of HNSCC, and the association of HPV with PI3K pathway mutations, this rationale is strengthened. In a directed analysis of 15 genes in 64 HNSCC tumors, PIK3CA mutation was the most abundant mutation, found at a much higher frequency in the oropharynx than in any other primary site (McBride et al , ). This observation is consistent with a putative association between higher rates of HPV infection in oropharynx than in other head and neck cancer anatomic sites (Gillison et al , ), and higher rates of PIK3CA mutation in HPV+ HNSCC than in HPV‐ HNSCC (Lui et al , ; Nichols et al , ).…”