Noormohammadpour Pardis, Hueniken Katrina, Pienkowski Martha, Huang Shao Hui, Yuan Baijiang, Grant Benjamin, Yao Christopher, Hope Andrew, Tsai Jillian, McPartlin Andrew, Goldstein David, Hosni Ali, de Almeida John R, Grant Robert C, Liu Geoffrey, Li Yuchen
Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
Neoplasia. 2025 Aug;66:101178. doi: 10.1016/j.neo.2025.101178. Epub 2025 May 16.
Systemic inflammatory response (SIR) markers are prognostic in various cancers. In a prospective cohort study (2006-2019) involving 2044 head and neck squamous cell carcinomas (HNSCC) patients, we assessed the prognostic associations of SIR markers at diagnosis, including NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio), LMR (lymphocyte-to-monocyte ratio), NMR (neutrophil-to-monocyte ratio), SII (systemic immune-inflammation index), eosinophil and WBC (white blood cell) levels, with progression-free (PFS) and overall survival (OS). Training (two-thirds randomly selected patients) and withheld test sets were created. Separate multivariable Cox regression models by HPV status were created for each of the seven SIR markers for the training set, and validated in the withheld test set. We found that the majority of SIR markers are strongly and significantly associated with OS and PFS in HPV-positive HNSCC patients, while the results were less significant or of lesser magnitude of association in the HPV-negative HNSCC patients. Despite validating these prognostic associations, the addition of SIR markers to a clinical prognostic model did not significantly improve predictive performance for PFS/OS. Our study demonstrates that SIR markers may have a greater impact on the survival of HPV-positive HNSCC, and less so for HPV-negative HNSCCs. These results suggest differential prognostic impact of inflammation between HPV-driven HNSCCs and non-HPV-driven HNSCCs. Although biologically relevant, these associations do not improve survival prognostication in the clinical setting.
全身炎症反应（SIR）标志物在多种癌症中具有预后价值。在一项涉及2044例头颈部鳞状细胞癌（HNSCC）患者的前瞻性队列研究（2006 - 2019年）中，我们评估了诊断时SIR标志物的预后相关性，包括中性粒细胞与淋巴细胞比值（NLR）、血小板与淋巴细胞比值（PLR）、淋巴细胞与单核细胞比值（LMR）、中性粒细胞与单核细胞比值（NMR）、全身免疫炎症指数（SII）、嗜酸性粒细胞和白细胞（WBC）水平与无进展生存期（PFS）和总生存期（OS）的关系。创建了训练集（随机选择三分之二的患者）和保留测试集。针对训练集中的七个SIR标志物，分别根据HPV状态创建了多变量Cox回归模型，并在保留测试集中进行了验证。我们发现，大多数SIR标志物与HPV阳性HNSCC患者的OS和PFS密切相关，而在HPV阴性HNSCC患者中，结果的相关性较弱或不太显著。尽管验证了这些预后相关性，但将SIR标志物添加到临床预后模型中并不能显著提高PFS/OS的预测性能。我们的研究表明，SIR标志物可能对HPV阳性HNSCC的生存影响更大，而对HPV阴性HNSCC的影响较小。这些结果表明，HPV驱动的HNSCC和非HPV驱动的HNSCC之间炎症的预后影响存在差异。尽管具有生物学相关性，但这些关联在临床环境中并不能改善生存预后。
