The incidence of human papilloma virus–mediated oropharyngeal squamous cell carcinoma (OPSCC) has increased over the past 40 years, particularly among young individuals with a favorable prognosis; however, current therapy often leads to unfortunate side effects, such as dysphagia. Despite the emphasis on dysphagia in previous studies, there is an important research gap in understanding the correlation between neuronal changes and patient-reported and functional outcomes in patients with OPSCC. To address this issue, we examined pathologic tissue samples from patients with OPSCC using multiplex immunofluorescence staining and machine learning to correlate tumor-associated neuronal changes with prospectively collected patient-reported and functional outcomes. We found that tumor enrichment of adrenergic (TH + ) and CGRP + sensory–afferent nerves correlated with poorer swallowing outcomes. Functional electromyography recordings showed correlations between growing (GAP43 + ) and immature cholinergic (ChAT + DCX + ) nerves and denervation patterns in survivors of OPSCC. A murine model of radiation-induced dysphagia further confirmed that immature cholinergic and CGRP + nerves were correlated with impaired swallowing. Preclinical interventional studies also supported the independent contributions of CGRP + and cholinergic (ChAT + ) nerves to dysphagia in treated mouse models of OPSCC. Our results suggest that CGRP + and ChAT + neuronal signaling play distinct roles in tumor- and radiation-induced dysphagia in OPSCC and offer a comprehensive dataset on the neural landscape of OPSCC. These insights may guide early interventions for swallow preservation and the repurposing of neurology-related drugs, such as CGRP blockers, in clinical oncology and survivorship.

中文翻译：

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神经景观与口咽鳞状细胞癌受照射患者的功能结果相关


在过去 40 年中，人瘤病毒介导的口咽鳞状细胞癌 （OPSCC） 的发病率有所增加，尤其是在预后良好的年轻人中;然而，目前的治疗往往会导致不幸的副作用，例如吞咽困难。尽管以前的研究强调吞咽困难，但在理解 OPSCC 患者神经元变化与患者报告和功能结果之间的相关性方面存在重要的研究空白。为了解决这个问题，我们使用多重免疫荧光染色和机器学习检查了 OPSCC 患者的病理组织样本，以将肿瘤相关神经元变化与前瞻性收集的患者报告和功能结果相关联。我们发现肾上腺素能 （TH + ） 和 CGRP + 感觉传入神经的肿瘤富集与较差的吞咽结果相关。功能性肌电图记录显示 OPSCC 幸存者生长 （GAP43 + ） 和未成熟胆碱能 （ChAT + DCX + ） 神经与去神经支配模式之间的相关性。辐射诱导吞咽困难的小鼠模型进一步证实，未成熟的胆碱能和 CGRP + 神经与吞咽受损相关。临床前干预研究还支持 CGRP + 和胆碱能 （ChAT + ） 神经对治疗后的 OPSCC 小鼠模型中吞咽困难的独立贡献。我们的结果表明，CGRP + 和 ChAT + 神经元信号在 OPSCC 中肿瘤和辐射诱导的吞咽困难中起着不同的作用，并提供了有关 OPSCC 神经景观的综合数据集。这些见解可以指导早期干预，以保护吞咽和重新利用神经病学相关药物，例如 CGRP 阻滞剂，用于临床肿瘤学和生存。