唐山地区EBV及HPV感染与口咽鳞癌预后相关性分析

Predictive value of EBV and HPV infection for prognosis of oropharyngeal squamous cell carcinoma in Tangshan Area

目的检测唐山地区口咽鳞癌(oropharyngeal squamous cell carcinoma,OPC)组织中EB病毒(Epstein-Barr virus,EBV)和人乳头瘤病毒(human papillomavirus,HPV)感染情况及其对疾病预后判断的价值。方法选取2003-01-01-2010-12-31唐山市协和医院明确诊断的OPC手术切除标本98例,分别采用原位杂交及PCR-反向点杂交方法检测蜡块组织中EB病毒编码的小RNA(EBV-encoded small RNA,EBER)及HPV感染情况,同时对所有患者进行电话随访。应用SPSS 18.0进行统计分析,Kaplan-Meier模型分析中位生存期,Log-rank检验比较生存曲线,Cox回归模型进行多因素分析。结果 98例OPC组织中29.6%(29/98)检测出HPV感染,4.1%(4/98)检测出EBER阳性;HPV感染与口咽癌患者的性别、年龄、饮酒状态、肿瘤部位、临床分期及分级均无明显相关性;HPV阳性病例以非吸烟者居多,明显高于吸烟者,P<0.001。Kaplan-Meier生存曲线显示,随访>30个月OPC患者中Ⅰ和Ⅱ期中位生存期为29个月,明显高于Ⅲ和Ⅳ期19个月,χ2=36.602,P<0.001;HPV阳性患者的中位生存期为35个月,高于HPV阴性患者23个月,χ2=34.413,P<0.001;病理分级为高、中分化患者的中位生存期分别为39和27个月,明显高于低分化的患者19个月,P<0.001。EBER表达与患者的各临床特征均无明显相关性;EBER阳性的OPC患者总体生存率与阴性患者比较差异无统计学意义,P=0.200。结论唐山地区OPC组织中存在一定程度的HPV及EBV感染情况,HPV阳性、临床分期早及分化程度高的OPC患者具有较好的预后。EBV感染对OPC患者的预后并无明显的判断价值。

OBJECTIVE To detect the infection of EB virus（EBV）and human papilloma virus（HPV）in oropharynx squamous cell carcinoma（OPC）tissues of Tangshan area and judge its predictive value for prognosis of disease.METHODS Totally 98 cases of oropharynx squamous cell carcinoma specimens were selected from January 1,2003 to December31,2010 in Tangshan Xiehe Hospital.In situ hybridization and PCR-reverse dot blot hybridization were used to detect the infection of EBV-encoded small RNA（EBER）and HPV in the wax blocks.All patients were followed up.Statistical analyses were conducted using SPSS version 18.0.The Kaplan-Meier method was used to estimate median overall survival（OS）and the Log-rank test to compare survival curves.Cox regression model was used for multivariate analysis.RESULTS Twenty-nine samples of all the 98 oropharyngeal squamous cell carcinoma specimens were detected the infection of HPV,the infection rate was 29.6%.Four samples were detected positive EBER and the infection rate was 4.1%（4/98）.HPV infection was not significantly correlated with patients＇ gender,age,alcohol drinking,clinical stage,tumor size,location,and differentiation.HPV-positive cases,mostly in non-smokers,were significantly higher than that of smokers（P〈0.001）.Kaplan-Meier survival curves showed that in the more than 30 months of follow-up study,the median survival time in stageⅠ and Ⅱ of patients with OPC was 29 months,significantly longer than the 19 months of stageⅢ and Ⅳ（P〈0.001）.The median survival time of HPV positive cases was 35 months,statistically significantly longer than that of HPV negative ones which was 23months（P〈0.001）.Differentiation of high and median tumors was with 39 and 27 months median survival time respectively,longer than poor differentiation cases of 19 months（P〈0.001）.There was no correlation with EBER expression and clinical characteristics.There was no significant statistical difference of the overall survival rate between EBER positive and negative ones in oropharyngeal squamous carcinoma patients.CONCLUSIONS There is a cetain degree of infection of HPV and EBV in oropharyngeal squamous cell carcinoma tissues in Tang Shan region.HPV positive,early clinical stage and higher differentiation of oropharyngeal squamous cell carcinoma had better prognosis.EBV infection has no significant prognostic value for patients of oropharyngeal squamous cell carcinoma.