术后辅助放疗可提高HPV16阴性Ⅱa期食管鳞癌患者根治术后的生存率
Postoperative adjuvant radiotherapy improves the survival of HPV16 negative esophageal squamous cell carcinoma at stageⅡa

摘要：目的 回顾性分析术后辅助放疗对HPV16相关Ⅱa(pT3)期食管鳞癌根治术后患者长期生存的价值。方法 选取2007年1月至2009年9月期间，西安交通大学第一附属医院术后病理分期为Ⅱa(pT3)期食管鳞癌患者的97例病理标本以及54例正常食管黏膜或癌旁组织标本，采用免疫组化法检测HPV16E6、p75NTR及P13K的表达，并分析HPV16、PI3K与患者的临床特征、预后之间的相关性，以及术后辅助放疗对Ⅱa(pT3)期食管鳞癌患者术后生存率的影响。结果 97例Ⅱa(pT3)期食管鳞癌组织的HPV16E6和PI3K的表达阳性率分别为64.9%、69.1%；全组患者5年生存率42.3%，中位生存期52个月；HPV16阴性与阳性的5年生存率分别为67.6%、25.3%，术后放疗与未放疗的5年生存率分别为60.9%和31.9%，差异均有统计学意义(P<0.05)。分层分析示，HPV16阴性者术后放疗与未放疗的5年生存率分别为69.0%和38.7%，差异有统计学意义(P=0.040)。亚组分析示，HPV16阴性组中年龄≤61.5岁、女性、无吸烟史者应用术后辅助放疗提高生存率更明显，差异均有统计学意义(P<0.05)。结论 HPV16可能是通过激活PI3K/AKT信号通路，改变了Ⅱa期食管鳞癌患者固有的辐射敏感性。术后辅助放疗只能提高HPV16阴性Ⅱa期食管鳞癌患者根治术后的生存率。
ABSTRACT: Objective To explore the prognostic factors and significance of postoperative adjuvant radiotherapy for HPV16-associated esophageal squamous cell carcinoma (ESCC) patients at UICC stage Ⅱa. Methods Pathological specimens of 97 patients with ESCC at stage IIa and esophageal mucosa or paracancerous tissues of 54 normal subjects in the First Affiliated Hospital of Xi’an Jiaotong University from January 2007 to September 2009 were retrospectively analyzed for the expressions of HPV16E6, p75NTR and PI3K using immunohistochemistry, their correlation with the patients’ clinical characteristics and prognosis, as well as the impact of postoperative adjuvant radiotherapy on the survival rate of patients with ESCC at stage Ⅱa. Results The expression of HPV E6 was 64.9% in ESCC. The 5-year overall survival rates was 42.3%, and the median was 52 months. The 5-year survival rates of HPV16 negative and HPV16 positive were 67.6% and 25.3%, respectively (P<0.001). The 5-year survival rates of adjuvant radiotherapy and non-radiotherapy were 60.9% and 31.9%, respectively (P=0.015). Stratification analysis showed that with or without adjuvant radiotherapy in HPV16 negative group, the 5-year survival rate was 69% and 38.7%, respectively (P=0.04). Subgroup analysis showed that postoperative adjuvant radiotherapy could only improve the 5-year survival rate of stage IIa ESCC patients who were HPV16 negative and ≤61.5 years old, or HPV16 negative females, or HPV16 negative non-smokers (P<0.05). Conclusion HPV16 infection may activate PI3K/AKT signaling pathway and alter the intrinsic radiosensitivity of patients at early stage in ESCC. Overall, postoperative adjuvant radiotherapy could improve the survival rate of HPV16 negative patients with ESCC