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炎症因子(IL-6、IL-8和TNF-α)在唾液中对人乳头瘤病毒相关口咽鳞状细胞癌患者放疗反应的预测和预后价值

Predictive and prognostic value of inflammatory factors (IL-6, IL-8, and TNF-α) in saliva for radiotherapy response in patients with HPV-associated oropharyngeal squamous cell carcinoma.

作者信息

Tan Li, Liu WenJuan, Sun QiChen, Shi Yan

机构信息

Qilu Medical University, No. 1678, Renmin West Road, Zibo, 255300, Shandong, China.

出版信息

Discov Oncol. 2025 Jul 18;16(1):1366. doi: 10.1007/s12672-025-02986-2.

Abstract

OBJECTIVE

This investigation focused on analyzing saliva inflammatory factors (IL-6, IL-8, and TNF-α) to predict radiotherapy response and determine prognostic value in individuals with HPV-linked oropharyngeal squamous cell carcinoma (OPSCC).

METHODS

Sixty patients diagnosed with HPV-associated OPSCC and treated with 3D conformal intensity-modulated radiotherapy at our hospital from June 2016 to June 2020 were selected, as well as 60 healthy individuals who underwent outpatient physical exams as the control group. The relationship between saliva IL-6, IL-8, and TNF-α and clinicopathological features was analyzed. The relationship between HPV status and radiotherapy response in OPSCC patients was analyzed, and the predictive value of saliva inflammatory factors on radiotherapy response was analyzed by ROC curves, and the factors influencing the prognosis of OPSCC were analyzed by Cox regression.

RESULTS

Saliva IL-6, IL-8, and TNF-α in OPSCC patients did not show any statistically significant differences when analyzed across different genders, ages, tumor sites, histological grades, tumor sizes, clinical stages, cervical lymph node metastasis, and HPV status. IL-6, IL-8, and TNF-α in OPSCC patients were higher than those in healthy individuals. Patients with HPV-positive OPSCC were more sensitive to radiotherapy compared to those with HPV-negative. Saliva TNF-α levels were elevated in the radiotherapy-sensitive OPSCC patients, with IL-6 and IL-8 levels being lower than those in radiotherapy-insensitive patients. For predicting radiotherapy response, the AUC for IL-6, IL-8, and TNF-α was 0.744, 0.750, and 0.742, respectively, with the combination yielding an AUC of 0.821. Among OPSCC patients, those who survived showed higher TNF-α levels in saliva and lower IL-6 and IL-8 levels compared with those died. Elevated TNF-α level in saliva and sensitivity to radiotherapy were protective factors affecting prognosis, and elevated IL-6 and IL-8 were risk factors.

CONCLUSION

Saliva IL-6, IL-8, and TNF-α are related to radiotherapy sensitivity and prognosis in patients with HPV-associated OPSCC, which can guide the selection of clinical treatment programs.

摘要

目的

本研究聚焦于分析唾液炎症因子(白细胞介素-6、白细胞介素-8和肿瘤坏死因子-α),以预测放疗反应并确定其在人乳头瘤病毒(HPV)相关的口咽鳞状细胞癌(OPSCC)患者中的预后价值。

方法

选取2016年6月至2020年6月在我院诊断为HPV相关OPSCC并接受三维适形调强放疗的60例患者,以及60例接受门诊体检的健康个体作为对照组。分析唾液白细胞介素-6、白细胞介素-8和肿瘤坏死因子-α与临床病理特征之间的关系。分析OPSCC患者HPV状态与放疗反应之间的关系,通过ROC曲线分析唾液炎症因子对放疗反应的预测价值,并通过Cox回归分析影响OPSCC预后的因素。

结果

在按不同性别、年龄、肿瘤部位、组织学分级、肿瘤大小、临床分期、颈部淋巴结转移和HPV状态分析时,OPSCC患者的唾液白细胞介素-6、白细胞介素-8和肿瘤坏死因子-α未显示出任何统计学上的显著差异。OPSCC患者的白细胞介素-6、白细胞介素-8和肿瘤坏死因子-α高于健康个体。与HPV阴性的OPSCC患者相比,HPV阳性的患者对放疗更敏感。放疗敏感的OPSCC患者唾液肿瘤坏死因子-α水平升高,白细胞介素-6和白细胞介素-8水平低于放疗不敏感患者。对于预测放疗反应,白细胞介素-6、白细胞介素-8和肿瘤坏死因子-α的曲线下面积(AUC)分别为0.744、0.750和0.742,三者联合的AUC为0.821。在OPSCC患者中,存活者唾液中的肿瘤坏死因子-α水平高于死亡者,白细胞介素-6和白细胞介素-8水平低于死亡者。唾液中肿瘤坏死因子-α水平升高和对放疗敏感是影响预后的保护因素,白细胞介素-6和白细胞介素-8升高是危险因素。

结论

唾液白细胞介素-6、白细胞介素-8和肿瘤坏死因子-α与HPV相关OPSCC患者的放疗敏感性和预后相关,可指导临床治疗方案的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb29/12274181/71dffbb1f28d/12672_2025_2986_Fig1_HTML.jpg

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