Transcriptomic Differences Related to Neck Pain in Patients with Oropharyngeal Squamous Cell Carcinoma

<b>Background/Objectives:</b> Neck-specific pain and disability are common and burdensome for survivors of oropharyngeal squamous cell carcinoma (OPSCC), yet the biological mechanisms underlying these symptoms remain poorly understood. While patient-reported outcomes (PROs) offer valuable insight into pain and function, their limited integration with molecular data restricts the development of targeted interventions. The purpose of this study was to explore transcriptomic differences associated with neck pain and disability in OPSCC survivors. <b>Methods</b>: Bulk RNA sequencing was performed on blood samples collected from OPSCC survivors either pre-radiation or more than one year post treatment. DESeq2 was used to determine differentially expressed genes between survivors reporting no versus any neck-related pain, as measured by the validated Neck Disability Index. Ingenuity Pathway Analysis was used to explore interaction among the genes. <b>Results</b>: We identified 24 significantly differentially expressed genes (adjusted <i>p</i> < 0.05) linked to hematopoietic, immune, and neuronal functions. Pathway analysis of the top 50 differentially expressed genes revealed overlap in interferon signaling, iron homeostasis, and blood cell development, suggesting molecular connectivity in hematologic and immunologic disease, cellular movement, and connective tissue disorders. <b>Conclusions</b>: These findings suggest the existence of molecular phenotypes associated with patient-reported neck pain and disability in OPSCC survivors and highlight the importance of integrating PROs with molecular profiling to better understand survivorship burden.