论文摘要
人乳头瘤病毒（human papillomavirus, HPV）是一类双链环状DNA病毒,研究认为其感染人体后与多种肿瘤的发生有关。1982年Syrjanen等首先发现HPV感染与食管癌发生具有相关性,此后,对探索HPV感染是否为食管癌病因的研究一直持续,但不同的结果间差异较大。广东省潮汕地区是我国唯一的沿海食管癌高发区,已有的研究表明,该地区食管癌及癌旁组织中HPV感染率较高,推测与该地区食管癌的发生有关。为了解HPV在潮汕食管癌中的感染现状,并进一步研究HPV感染在食管癌发生中的作用,本研究采用巢式PCR结合测序的方法检测HPV在食管癌及其癌旁配对正常组织以及正常食管粘膜组织中的感染情况,分析HPV感染的型别分布规律及HPV感染与临床表征间的相关性,在此基础上,探讨高危型HPV-16 DNA的整合在食管癌变中的作用。结果表明:（1） HPV在潮汕地区食管癌、癌旁配对正常组织以及正常食管粘膜组织中的感染率分别为77.36% （82/106）、80.19% （85/106）及33.00% （33/100）。其中,HPV在食管癌和癌旁配对正常组织中的感染率高于正常食管粘膜组织（P <0.001）,但癌和癌旁相比,感染率差别无统计学意义（P >0.05）。（2）食管癌患者中HPV的感染主要分布在3547岁年龄组,且随着患者年龄的增加HPV的感染率降低。吸烟的食管癌患者比不吸烟患者的HPV感染率高（84.91% VS 67.35%,P <0.05）,且吸烟组HPV感染风险为不吸烟组的3.27倍。HPV的感染与患者的性别、饮酒、肿瘤的病理分级以及淋巴结转移情况无关。经多因素分析发现,食管癌患者的年龄及吸烟是HPV感染的影响因素。（3） HPV的感染型别在食管癌中的分布从高到低依次为:HPV-16 （62.6%）、-58 （13.1%）、-18 （11.1%）、-33 （3.0%）、-31 （3.0%）、-11 （1.0%）。多重感染包括HPV-16/-18和HPV-16/-33。其中,以HPV-16/-18 （5.2%）两重感染为主。（4）高危型HPV-16 DNA在食管癌、癌旁正常组织以及正常人食管粘膜组织中的整合率分别是93.44% （57/61）、50.85% （30/59）和45.45% （10/22）。其中,HPV-16 DNA在癌组织中的整合率明显高于癌旁配对正常组织及正常人食管粘膜组织的整合率（P <0.01）,而癌旁正常和正常人食管粘膜组织间的整合率差别无统计学意义（P >0.05）。研究得出以下结论:①潮汕地区食管癌患者中癌组织及其癌旁配对组织中的HPV感染率较高。HPV感染主要分布在3547岁年龄组食管癌患者中,年龄及吸烟是其感染的影响因素;②高危型HPV-16、-58和-18型是该地区食管癌的主要感染型别;③高危型HPV-16 DNA在食管癌中的整合率较高,其与宿主细胞DNA的整合可能是导致食管癌发生的重要原因之一。
论文目录
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