Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial
Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial
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DOI：
10.1093/jnci/djn011
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发表时间：
2008-02-20
影响因子：
10.3
通讯作者：
Gillison, Maura L.
中科院分区：
文献类型：
--
作者：
Fakhry, Carole;Westra, William H.;Gillison, Maura L.
背景：回顾分析发现，与HPV阴性的头颈部鳞状细胞癌相比，HPV阳性的头颈部鳞状细胞癌患者的预后改善仍有待前瞻性临床试验的证实。方法我们前瞻性地评估了96例口咽或喉部HNSCC患者的肿瘤HPV状态与疗效和生存率的关系，这些患者参加了东部合作肿瘤组(ECOG)的II期试验，他们接受了两个周期的诱导化疗，用静脉注射紫杉醇和卡铂，然后同时每周静脉注射紫杉醇和标准分割放射治疗。采用多重聚合酶链式反应和原位杂交法检测肿瘤组织中HPV的致癌类型。通过Kaplan-Meier分析评估HPV阳性和HPV阴性患者的两年总生存率和无进展生存率。在调整了年龄、ECOG表现状态、分期和其他协变量后，使用多变量COX比例风险模型估计了HPV阳性和HPV阴性患者死亡和进展的相对风险。结果原位杂交和聚合酶链式反应检测结果显示，口咽部或喉部HNSCC患者中，致癌HPV16、33、35型基因组DNA位于40%的肿瘤细胞核内(95%可信区间=30%~50%)。与HPV阴性肿瘤患者相比，HPV阳性肿瘤患者诱导化疗后有效率(82%vs 55%，差异=27%，95%CI=9.3%~44.7%，P=.01)和放化疗后有效率(84%vs 57%，差异=27%，95%CI=9.7%~44.3%，P=.007)。中位随访39.1个月后，HPV阳性肿瘤患者的总生存率有所提高(2年总生存率=95%[95%CI=87%至100%]vs 62%[95%CI=49%至74%]，差异=33%，95%CI=18.6%至47.4%，P=.005，LOG检验)，调整年龄、肿瘤分期和ECOG表现状态后，进展风险较低(风险比[HR]=0.27，95%CI=0.10至0.75)。结论口咽部HNSCC患者中，肿瘤HPV状态与疗效和生存期密切相关。
Background The improved prognosis for patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) relative to HPV-negative HNSCC observed in retrospective analyses remains to be confirmed in a prospective clinical trial.Methods We prospectively evaluated the association of tumor HPV status with therapeutic response and survival among 96 patients with stage III or IV HNSCC of the oropharynx or larynx who participated in an Eastern Cooperative Oncology Group (ECOG) phase II trial and who received two cycles of induction chemotherapy with intravenous paclitaxel and carboplatin followed by concomitant weekly intravenous paclitaxel and standard fractionation radiation therapy. The presence or absence of HPV oncogenic types in tumors was determined by multiplex polymerase chain reaction (PCR) and in situ hybridization. Two-year overall and progression-free survival for HPV-positive and HPV-negative patients were estimated by Kaplan-Meier analysis. The relative hazard of mortality and progression for HPV-positive vs HPV-negative patients after adjustment for age, ECOG performance status, stage, and other covariables was estimated by use of a multivariable Cox proportional hazards model. All statistical tests were two-sided.Results Genomic DNA of oncogenic HPV types 16, 33, or 35 was located within tumor cell nuclei of 40% (95% confidence interval [CI] = 30% to 50%) of patients with HNSCC of the oropharynx or larynx by in situ hybridization and PCR. Compared with patients with HPV-negative tumors, patients with HPV-positive tumors had higher response rates after induction chemotherapy (82% vs 55%, difference = 27%, 95% CI = 9.3% to 44.7%, P = .01) and after chemoradiation treatment (84% vs 57%, difference = 27%, 95% CI = 9.7% to 44.3%, P = .007). After a median follow-up of 39.1 months, patients with HPV-positive tumors had improved overall survival (2-year overall survival = 95% [ 95% CI = 87% to 100%] vs 62% [ 95% CI = 49% to 74%], difference = 33%, 95% CI = 18.6% to 47.4%, P = .005, log-rank test) and, after adjustment for age, tumor stage, and ECOG performance status, lower risks of progression (hazard ratio [HR] = 0.27, 95% CI = 0.10 to 0.75), and death from any cause (HR = 0.36, 95% CI = 0.15 to 0.85) than those with HPV-negative tumors.Conclusion For patients with HNSCC of the oropharynx, tumor HPV status is strongly associated with therapeutic response and survival.