Human Papillomavirus Status and the Risk of Cerebrovascular Events Following Radiation Therapy for Head and Neck Cancer.
Human Papillomavirus Status and the Risk of Cerebrovascular Events Following Radiation Therapy for Head and Neck Cancer.
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DOI：
10.1161/jaha.117.006453
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发表时间：
2017-08-30
影响因子：
5.4
通讯作者：
Neilan TG
中科院分区：
文献类型：
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作者：
Addison D;Seidelmann SB;Janjua SA;Emami H;Staziaki PV;Hallett TR;Szilveszter B;Lu MT;Cambria RP;Hoffmann U;Chan AW;Wirth LJ;Neilan TG
放射治疗（RT）是头颈癌的标准治疗;然而，它与炎症，加速动脉粥样硬化和脑血管事件（CVEs;中风或短暂性脑缺血发作）有关。人乳头瘤病毒（HPV）在近一半的头颈部癌症中发现，并与炎症和动脉粥样硬化有关。HPV是否会增加RT后发生CVEs的风险尚不清楚。使用机构数据库，我们确定了2002年至2012年接受RT治疗的所有连续患者，这些患者接受了HPV检测。关注的结局是缺血性卒中和短暂性脑缺血发作的复合终点，HPV和CVE之间的相关性采用考克斯比例风险模型、竞争风险分析和逆概率加权进行评估。总体而言，326名接受头颈部癌症RT的参与者接受了HPV检测（年龄59±12岁，75%为男性，9%患有糖尿病，45%患有高血压，61%为吸烟者），其中191人（59%）为肿瘤HPV阳性。HPV阳性和阴性患者之间的CVE的传统风险因素相似。在中位随访3.4年期间，有18例缺血性卒中和5例短暂性脑缺血发作（事件发生率为每年1.8%）。HPV阳性患者的年事件发生率高于HPV阴性患者（2.6% vs 0.9%，P=0.002）。在多变量模型中，HPV阳性状态与CVEs风险增加>4倍相关（风险比：4.4; 95%置信区间，1.5-13.2; P=0.008）。在这项研究中，HPV阳性状态与头颈部癌RT后中风或短暂性脑缺血发作的风险增加相关。
Radiation therapy (RT) is a standard treatment for head and neck cancer; however, it is associated with inflammation, accelerated atherosclerosis, and cerebrovascular events (CVEs; stroke or transient ischemic attack). Human papillomavirus (HPV) is found in nearly half of head and neck cancers and is associated with inflammation and atherosclerosis. Whether HPV confers an increased risk of CVEs after RT is unknown. Using an institutional database, we identified all consecutive patients treated with RT from 2002 to 2012 for head and neck cancer who were tested for HPV. The outcome of interest was the composite of ischemic stroke and transient ischemic attack, and the association between HPV and CVEs was assessed using Cox proportional hazard models, competing risk analysis, and inverse probability weighting. Overall, 326 participants who underwent RT for head and neck cancer were tested for HPV (age 59±12 years, 75% were male, 9% had diabetes mellitus, 45% had hypertension, and 61% were smokers), of which 191 (59%) were tumor HPV positive. Traditional risk factors for CVEs were similar between HPV‐positive and ‐negative patients. Over a median follow‐up of 3.4 years, there were 18 ischemic strokes and 5 transient ischemic attacks (event rate of 1.8% per year). The annual event rate was higher in the HPV‐positive patients compared with the HPV‐negative patients (2.6% versus 0.9%, P=0.002). In a multivariable model, HPV‐positive status was associated with a >4 times increased risk of CVEs (hazard ratio: 4.4; 95% confidence interval, 1.5–13.2; P=0.008). In this study, HPV‐positive status is associated with an increased risk of stroke or transient ischemic attack following RT for head and neck cancer.