Background/Objectives: Oropharyngeal squamous cell carcinoma (OPSCC) management has shifted following recognition of HPV-driven disease. Neoadjuvant chemotherapy (NAC) has historically failed to improve overall survival (OS) in mixed head and neck cohorts, although contemporary HPV-stratified series suggest NAC may enable treatment de-escalation. We aimed to narratively synthesize OPSCC-specific evidence on NAC focusing on primary and nodal response, pathologic complete response (pCR), survival, and functional outcomes.Methods: We conducted a narrative review of PubMed, selecting primary studies in which OPSCC outcomes were reported separately (surgery- or chemoradiotherapy [CRT]-based strategies; HPV status when available). We extracted study design, treatment regimens, response outcomes, survival, and toxicity data.Results: Pre-HPV studies showed variable responses and no consistent OS advantage over locoregional therapy. In the HPV era, non-comparative cohorts of NAC followed by transoral surgery reported substantial downstaging and high pCR rates at both the primary site and regional nodes, with 3–5-year OS frequently ≥80%. NAC+CRT paradigms demonstrated high clinical CR rates and OS exceeding 80–90%, and lower feeding-tube dependence and reduced swallowing morbidity in de-escalated regimens. Comparative retrospective series suggest NAC + surgery may be associated with lower rates of distant metastases and feeding-tube use compared with CRT or upfront surgery, although interpretation is limited by selection bias, regimen heterogeneity, and small sample sizes.Conclusions: While randomized trials have not established an OS advantage for NAC over standard CRT in head and neck cancer overall, HPV-positive OPSCC shows emerging evidence that systemic intensification with NAC may enable surgical and/or radiation de-escalation with promising oncologic and functional outcomes.
背景/目的：随着HPV驱动型口咽鳞状细胞癌（OPSCC）的明确，其治疗策略已发生转变。尽管新辅助化疗（NAC）在混合型头颈癌队列中历来未能改善总生存期（OS），但当代基于HPV分层的系列研究表明，NAC可能有助于实现治疗降级。本研究旨在通过叙述性综述，系统梳理针对OPSCC的NAC相关证据，重点关注原发灶和淋巴结反应、病理完全缓解（pCR）、生存结局及功能预后。 方法：我们对PubMed数据库进行了叙述性综述，筛选出单独报告OPSCC结局的原始研究（包括基于手术或放化疗[CRT]的策略；若可获得，则纳入HPV状态信息）。提取内容包括研究设计、治疗方案、反应结局、生存数据及毒性资料。 结果：HPV时代前的研究显示，NAC反应不一，且相较于局部区域治疗未能带来一致的OS获益。在HPV时代，采用NAC后行经口手术的非对照队列研究显示，原发灶和区域淋巴结均出现显著降期，且pCR率较高，3-5年OS常≥80%。NAC联合CRT的治疗模式显示出较高的临床完全缓解率和超过80-90%的OS，在降级治疗方案中，饲管依赖率更低，吞咽功能障碍减轻。回顾性对比研究提示，与单纯CRT或直接手术相比，NAC联合手术可能具有较低的远处转移率和饲管使用率，但该结论受选择偏倚、方案异质性及样本量较小的限制，需谨慎解读。 结论：尽管随机试验尚未证实NAC在整体头颈癌治疗中相对于标准CRT具有OS优势，但HPV阳性OPSCC的新证据表明，采用NAC进行系统强化治疗，可能为手术和/或放疗降级创造条件，并在肿瘤学结局和功能预后方面展现出良好前景。
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