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人乳头瘤病毒阳性头颈部癌的不良预后因素:哪些患者可能不适合降阶梯治疗?

Poor prognostic factors in human papillomavirus-positive head and neck cancer: who might not be candidates for de-escalation treatment?

机构信息

Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.

Department of Otorhinolaryngology, Seoul National University Hospital, Seoul, Korea.

出版信息

Korean J Intern Med. 2019 Nov;34(6):1313-1323. doi: 10.3904/kjim.2017.397. Epub 2018 Nov 16.

Abstract

BACKGROUND/AIMS: Since patients with human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) have favorable outcomes after treatment, treatment de-escalation for these patients is being actively investigated. However, not all HPV-positive HNSCCs are curable, and some patients have a poor prognosis. The purpose of this study was to identify poor prognostic factors in patients with HPV-positive HNSCC.

METHODS

Patients who received a diagnosis of HNSCC and tested positive for HPV from 2000 to 2015 at a single hospital site (n = 152) were included in this retrospective analysis. HPV typing was conducted using the HPV DNA chip assay or liquid bead microarray system. Expression of p16 in the tumors was assessed by immunohistochemistry. To determine candidate factors associated with overall survival (OS), univariate and multivariable Cox regression analyses were performed.

RESULTS

A total of 152 patients with HPV-positive HNSCC were included in this study; 82.2% were male, 43.4% were current or former smokers, and 84.2% had oropharyngeal cancer. By univariate analysis, old age, performance status ≥ 1, non-oropharyngeal location, advanced T classification (T3-4), and HPV genotype 18 were significantly associated with poor OS. By multivariable analysis, performance status ≥ 1 and non-oropharyngeal location were independently associated with shorter OS (hazard ratio [HR], 4.36, p = 0.015; HR, 11.83, p = 0.002, respectively). Furthermore, HPV genotype 18 positivity was also an independent poor prognostic factor of OS (HR, 10.87, p < 0.001).

CONCLUSION

Non-oropharyngeal cancer, poor performance status, and HPV genotype 18 were independent poor prognostic factors in patients with HPV-positive HNSCC. Patients with these risk factors might not be candidates for de-escalation treatment.

摘要

背景/目的:由于人乳头瘤病毒(HPV)相关头颈部鳞状细胞癌(HNSCC)患者经治疗后预后良好,因此目前正在积极研究对这些患者进行治疗降级。然而,并非所有 HPV 阳性的 HNSCC 都可治愈,部分患者预后较差。本研究旨在确定 HPV 阳性 HNSCC 患者的不良预后因素。

方法

本回顾性分析纳入了 2000 年至 2015 年期间在单一医院就诊、经诊断患有 HNSCC 且 HPV 检测阳性的 152 例患者。HPV 分型采用 HPV DNA 芯片检测或液芯微珠系统检测。通过免疫组织化学法检测肿瘤中 p16 的表达。采用单变量和多变量 Cox 回归分析确定与总生存(OS)相关的候选因素。

结果

本研究共纳入 152 例 HPV 阳性 HNSCC 患者;82.2%为男性,43.4%为现吸烟或既往吸烟者,84.2%患有口咽癌。单因素分析显示,年龄较大、体力状况≥1 分、非口咽部位、T 分期较晚(T3-4)和 HPV 基因型 18 与较差的 OS 显著相关。多因素分析显示,体力状况≥1 分和非口咽部位与较短的 OS 独立相关(风险比[HR],4.36,p = 0.015;HR,11.83,p = 0.002)。此外,HPV 基因型 18 阳性也是 OS 的独立不良预后因素(HR,10.87,p < 0.001)。

结论

非口咽癌、体力状况差和 HPV 基因型 18 是 HPV 阳性 HNSCC 患者的独立不良预后因素。具有这些风险因素的患者可能不适合进行降级治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e4d/6823569/e8d57de8a326/kjim-2017-397f1.jpg

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