49例口咽鳞癌与高危型HPV感染的关联分析  

Correlation analysis of 49 cases of oropharyngeal squamous cell carcinoma and high-risk HPV infection

作　　者：杨苏梅 吴蒙[2] 韩凤艳[3] 张玲[3] 杨俊泉[4] 刘宏侠[3] YANG Su-mei;WU Meng;HAN Feng-yan;ZHANG Ling;YANG Jun-quan;LIU Hong-xia(Tangshan People’s Hospital,Tangshan 063001,P.R.China;Pathological Teaching and Research Division,Department of Basic Medicine,Tangshan Vocational and Technical College,Tangshan 063004,P.R.China;Department of Pathology,Tangshan Union Hospital,Tangshan 063004,P.R.China)

机构地区：[1]唐山市人民医院呼吸内科,河北唐山063001 [2]唐山职业技术学院基础医学部病理教研室,河北唐山063004 [3]唐山市协和医院病理科,河北唐山063004 [4]唐山市人民医院放化疗科,河北唐山063001

出　　处：《中华肿瘤防治杂志》2020年第21期1710-1717,共8页Chinese Journal of Cancer Prevention and Treatment

基　　金：河北省科技厅2016年度省级科技计划(162777214)。

摘　　要：目的高危型人乳头瘤病毒(human papillomavirus,HPV)感染与多种头颈部鳞癌(head and neck squamous cell carcinoma,HNSCC)的发生有关,口咽鳞癌(oropharyngeal squamous cell carcinoma,OPSCC)是HNSCC中的常见类型。本研究检测OPSCC组织中HPV及p53、p21、Cdc2蛋白的表达情况,探讨OPSCC预后影响因素及其临床检测价值。方法收集2012-01-01-2017-12-31唐山市协和医院头颈病理研究基地临床资料完整的OPSCC蜡块49例。采用RNAscope法检测肿瘤组织中HPV 16型、18型的E6、E7mRNA,免疫组化SP法观察p53、p21及Cdc2蛋白表达,对所有病例进行生存情况随访。Kaplan-Meier法分析中位生存时间,Log-rank检验进行预后单因素分析,Cox回归模型进行多因素分析。结果HPV-DNA检测阳性患者28.6%(14/49),阴性为71.4%(35/49);所有病例进行HPV16型E6、E7mRNA检测,阳性率为40.8%(20/49),其中11例同时为HPV 16DNA阳性;HPV 18-mRNA阳性患者4.08%(2/49);HPV16/18mRNA检测阴性患者55.1%(27/49);HPV检出多为非吸烟组患者68.8%(11/16),高于吸烟组患者33.3%(10/33),χ^2=5.463,P=0.019,差异有统计学意义;HPV检出与患者性别、年龄、饮酒、肿瘤分化程度及临床分期均无关,均P>0.05;p53在OPSCC组织中的表达率为63.3%(31/49),p21为65.3%(32/49),Cdc2为67.3%(33/49)。p53、p21及Cdc2蛋白表达与患者性别、年龄、吸烟、饮酒、肿瘤分化程度及临床分期无关,均P>0.05;HPV检出与p53、p21及Cdc2蛋白表达无关,均P>0.05;Cox多因素回归分析提示HPV检出(HR=0.275,95%CI:0.146~0.517)、肿瘤分化程度(HR=1.751,95%CI:1.231~2.492)、分期(HR=3.268,95%CI:1.758~6.074)及Cdc2蛋白表达(HR=1.804,95%CI:0.990~3.286)与患者生存期有关,均P<0.05。结论HPV阳性OPSSC多为非吸烟患者;HPV阴性、分化程度低、临床分期晚及Cdc2阳性表达的患者提示预后不良,临床需加强随访。OBJECTIVE High risk human papillomavirus(HPV)infection is associated with the development of multiple head and neck squamous cell carcinomas(HNSCC).Oropharyngeal squamous cell carcinoma(OPSCC)is a common type of HNSCC.In this study,HPV infection and the expression of p53,p21 and Cdc2 protein in OPSCC tissues was detected,and the prognostic factors and clinical detection value of OPSCC were discussed.METHODS Totally 49 cases with complete clinical data of OPSCC wax block were collected from of Tangshan Xiehe Hospital head and neck pathology research base from January 1,2012 to December 31,2017.The expression of E6 and E7 mRNA of HPV 16 and HPV 18 in tumor tissue was detected by RNAscope in situ hybridization,and the expression of p53,p21 and Cdc2 protein was observed by SP immunohistochemical method.All cases were followed up for survival.Using SPSS24.0 statistical software,median survival time was analyzed with Kaplan-Meier method.The Log-rank test was used for single factor analysis and Cox Regression model was used to analyze multiple factors of prognosis.RESULTS HPV-DNA detection was positive in 28.6%(14/49)and negative in 71.4%(35/49).All cases were tested for HPV16 E6 and E7 mRNA,and the positive rate was 40.8%(20/49),among which 11 cases were HPV 16 DNA positive.HPV 18-mRNA positive patients were4.08%(2/49).HPV16/18 mRNA negative patients accounted for 55.1%(27/49).The prevalence of HPV was 68.8%(11/16)in the non-smoking Group,higher than in smoking group 33.3%(10/33),χ^2=5.463,P<0.05,with statistically significant difference.The detection of HPV was not related to gender,age,drinking,tumor differentiation degree and clinical stage,P>0.05.The expression rate of p53 was 63.3%(31/49),p21 was 65.3%(32/49),and cdc2 was 67.3%(33/49).The expression of p53,p21 and Cdc2 was not related to gender,age,smoking,drinking,tumor differentiation and clinical stage,P>0.05.HPV infection was not associated to the expression of p53,p21 and Cdc2,P>0.05.Cox multifactor regression analysis showed that HPV infection(HR=0.275,95%C

关 键 词：RNAscope原位杂交 人乳头瘤病毒 CDC2 口咽鳞癌 预后 

分 类 号：R739.6[医药卫生—肿瘤]