We analyzed transcriptional data from 104 HPV+ (Human papillomavirus) HNSCC (head and neck squamous cell carcinoma) tumors together with two publicly available sources to identify highly robust transcriptional programs (modules) which could be detected consistently despite heterogeneous sequencing and quantification methodologies. Among 22 modules identified, we found a single module that naturally subclassifies HPV+ HNSCC tumors based on a bimodal pattern of gene expression, clusters all atypical features of HPV+ HNSCC biology into a single subclass, and predicts patient outcome in four independent cohorts. The subclass-defining gene set was strongly correlated with Nuclear factor kappa B (NF-κB) target expression. Tumors with high expression of this NF-κB module were rarely associated with activating PIK3CA alterations or viral integration, and also expressed higher levels of HPHPV E2 and had decreased APOBEC mutagenesis. Alternatively, they harbored inactivating alterations of key regulators of NF-κB, TNF receptor associated factor 3 (TRAF3), and cylindromatosis (CYLD), as well as retinoblastoma protein (RB1). HPV+ HNSCC cells in culture with experimental depletion of TRAF3 or CYLD displayed increased expression of the subclass-defining genes, as well as robust radio-sensitization, thus recapitulating both the tumor transcriptional state and improved treatment response observed in patient data. Across all gene sets investigated, methylation to expression correlations were the strongest for the subclass-defining, NF-κB-related genes. Increased tumor-infiltrating CD4+ T cells and increased Estrogen receptors alpha (ERα) expression were identified in NF-κB active tumors. Based on the relatively high rates of cure in HPV+ HNSCC, deintensification of therapy to reduce treatment-related morbidity is being studied at many institutions. Tumor subclassification based on oncogenic subtypes may help guide the selection of therapeutic intensity or modality for patients with HPV+ HNSCC.
Key Points Our findings suggest that primary ciliary dyskinesia (PCD)‐related chronic rhinosinusitis (CRS) has a more significant impact on quality of life than CRS without nasal polyps and cystic fibrosis (CF). PCD and CF have similar mucociliary clearance defects, yet sinonasal symptom severity varies between the two.
KEY POINTS Left‐hand‐dominant (LHD) respondents reported higher rates of training difficulties because of handedness differences. LHD respondents cited particular difficulty with functional endoscopic sinus surgery. Both LHD and right‐hand‐dominant respondents perceived a need for laterality‐specific training during residency.
Granulomatosis with polyangiitis is a rare autoimmune disease that affects small to medium-sized blood vessels throughout the body. Here, we present a case of an infratemporal mass that was the result of granulomatosis with polyangiitis. A 51-year-old male presented to the emergency department due to right cheek and facial pain that he had been experiencing for 2 to 3 months. An MRI revealed a mass within the right infratemporal and pterygopalatine fossae extending into the inferior right orbital fissure along the maxillary division of the trigeminal nerve (V2) and the vidian nerve causing concern for malignancy. Histology from an endoscopic biopsy demonstrated multiple arteries with luminal obliteration with non-necrotizing granulomas. The patient was started on steroids and immunosuppressive therapy, which improved his symptoms and decreased the size of the residual mass. This case illustrates the need for laboratory testing, imaging, and biopsy of the involved tissue in cases where GPA is suspected to prevent treatment delays that could lead to the destruction of vital organs.
Incidence of human papillomavirus positive (HPV+) head and neck squamous cell carcinoma (HNSCC) has dramatically increased in the U.S. surpassing cervical cancer since 2012. Among HNSCC, HPV+ HNSCC patients have a favorable prognosis; however, approximately 20-30% suffer recurrence. Given the morbidity of current therapy, therapeutic de-escalation for HPV+ HNSCC is being explored in many clinical trials but is hampered by absence of accurate molecular classifiers to identify tumors at high and low risk of recurrence. Being able to risk stratify patients can help with therapeutic decisions, maintain high cure rates and decrease treatment associated complications. We assemble a NanoString panel to capture our recently developed NF-κB RNA signature that can distinguish patients requiring aggressive therapy from patients who are appropriate for reduced intensity treatment. Our custom gene set can select HPV+ head and neck cancer patients that may benefit from therapy de-escalation. Several advantages of using a NanoString technology, including smaller amounts of patient samples and less processing time that allow real-time patient-specific results. This makes our Nanostring panel suitable to be used in clinic to identify HPV+ head and neck cancer patients for therapeutic de-escalation without compromising their survival. Citation Format: Sulgi Kim, Travis Schrank, Aditi Kothari, Hina Rehmani, Jason Tasoulas, Xue Li, Wendell Yarbrough, Natalia Isaeva. Novel risk stratification utilizing NanoString for HPV+ head and neck cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2217.
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