Human papillomavirus and survival of patients with oropharyngeal cancer.
Human papillomavirus and survival of patients with oropharyngeal cancer.
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DOI：
10.1056/nejmoa0912217
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发表时间：
2010-07-01
期刊：
影响因子：
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通讯作者：
Gillison ML
中科院分区：
文献类型：
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作者：
Ang KK;Harris J;Wheeler R;Weber R;Rosenthal DI;Nguyen-Tân PF;Westra WH;Chung CH;Jordan RC;Lu C;Kim H;Axelrod R;Silverman CC;Redmond KP;Gillison ML
人乳头状瘤病毒（HPV）引起的口咽鳞状细胞癌与良好的生存率相关，但肿瘤HPV状态的独立预后意义仍不清楚。我们对III期或IV期口咽部鳞状细胞癌患者肿瘤HPV状态与生存率之间的关系进行了回顾性分析，这些患者参加了一项随机试验，比较了加速分割放疗（通过伴随加强放疗加速）与标准分割放疗，每种放疗均联合顺铂治疗头颈部鳞状细胞癌患者。比例风险模型用于比较HPV阳性癌症患者和HPV阴性癌症患者的死亡风险。中位随访期为4.8年。接受加速分割放疗组和接受标准分割放疗组的3年总生存率相似（70.3% vs. 64.3%; P = 0.18;加速分割放疗死亡的风险比为0.90; 95%置信区间[CI]，0.72 - 1.13），以及高级别急性和晚期毒性事件的发生率。共有63.8%的口咽癌患者（323例中的206例）有HPV阳性肿瘤;这些患者的3年总生存率较好（82.4%，HPV阴性肿瘤患者为57.1%; P<0.001，通过对数秩检验），并且在调整年龄、种族、肿瘤和淋巴结分期、烟草暴露和治疗分配后，死亡风险降低58%（风险比，0.42; 95%CI，0.27 - 0.66）。死亡风险随着吸烟每增加一包-年而显著增加。使用递归分割分析，我们根据以下四个因素将患者分为低、中、高死亡风险：HPV状态、吸烟包年数、肿瘤分期和淋巴结分期。肿瘤HPV状态是口咽癌患者生存的一个强有力的独立预后因素。
Oropharyngeal squamous-cell carcinomas caused by human papillomavirus (HPV) are associated with favorable survival, but the independent prognostic significance of tumor HPV status remains unknown. We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a randomized trial comparing accelerated-fractionation radiotherapy (with acceleration by means of concomitant boost radiotherapy) with standard-fractionation radiotherapy, each combined with cisplatin therapy, in patients with squamous-cell carcinoma of the head and neck. Proportional-hazards models were used to compare the risk of death among patients with HPV-positive cancer and those with HPV-negative cancer. The median follow-up period was 4.8 years. The 3-year rate of overall survival was similar in the group receiving accelerated-fractionation radiotherapy and the group receiving standard-fractionation radiotherapy (70.3% vs. 64.3%; P = 0.18; hazard ratio for death with accelerated-fractionation radiotherapy, 0.90; 95% confidence interval [CI], 0.72 to 1.13), as were the rates of high-grade acute and late toxic events. A total of 63.8% of patients with oropharyngeal cancer (206 of 323) had HPV-positive tumors; these patients had better 3-year rates of overall survival (82.4%, vs. 57.1% among patients with HPV-negative tumors; P<0.001 by the log-rank test) and, after adjustment for age, race, tumor and nodal stage, tobacco exposure, and treatment assignment, had a 58% reduction in the risk of death (hazard ratio, 0.42; 95% CI, 0.27 to 0.66). The risk of death significantly increased with each additional pack-year of tobacco smoking. Using recursive-partitioning analysis, we classified our patients as having a low, intermediate, or high risk of death on the basis of four factors: HPV status, pack-years of tobacco smoking, tumor stage, and nodal stage. Tumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal cancer.