Regional Lymph Node Metastases Oncogenic Mutations Compared to Primary Tumors in HPV+ Oropharynx Patients.

6078 Background: Residual disease after concurrent chemoradiation in locally advanced Head and Neck cancer is typically contained in involved lymph nodes (LNs), with primary tumors (PTs) showing complete response to treatment. This resistant phenotype in LNs is not well characterized. Clonal genomic evolution in node metastases may explain this phenotype. Methods: PTs and matched LNs from consecutive patients who underwent trans-oral robotic surgery with modified neck dissections as primary therapy were tested using NextGen sequencing using the Oncomine Comprehensive Assay run on the Ion Torrent S5 system. This platform detects genetic mutations in 143 known cancer related genes. Tumors from patients treated with primary surgery were used given the need for sufficient tumor content to run the assay. Results were interpreted using the Ion Reporter Software. Results: A total of 21 patients had sufficient tumor content in FFPE samples that passed QC testing. Eight (38%) matched sets of PTs and LNs displayed the same mutation profile. LNs from four patients (19%) showed loss of mutations detected in primary tumors. Nine patients (43%) showed gain of mutations in neck LNs compared to PTs. Genes showing gain of mutation in LNs included: TP53 (4), PIK3CA (3), FBXW7 (3), VHL (1), PTEN (1), JAK3 (1), and MAPK1 (1). Conclusions: Gain of mutations in regional LNs was detected in almost half of all HPV-positive oropharynx patients. Gain of mutations in genes such as TP53 and PIK3CA may define a resistant genotype when such patients are treated with primary chemoradiation.