人乳头状瘤病毒感染与子宫颈癌发病关系的探讨

应用多重引物人乳头状瘤病毒（ＨＰＶ）６Ｂ／１１、１６、１８　型聚合酶链反应（ＰＣＲ）技术检测９９例不同宫颈病变宫颈组织中人乳头状瘤病毒ＤＮＡ（ＨＰＶＤＮＡ）。其中宫颈湿疣２０例，宫颈上皮内瘤变（ＣＩＮ）１～２级（ＣＩＮ＿（１～２））１８例，ＣＩＮ３级（ＣＩＮ＿３）２０例，宫颈癌２３例和正常对照１８例。结果：上述宫颈组织中ＨＰＶＤＮＡ总检出率分别为８５．０％，８３．３％，８０．０％，８７．０％和２７．８％。宫颈各病变组中ＨＰＶＤＮＡ的检出率均显著高于对照组（Ｐ＜０．０１）。宫颈湿疣及ＣＩＮ＿（１～２）中ＨＰＶ６Ｂ／１１型检出率分别为８５．０％和７２．３％，ＣＩＮ＿３和宫颈癌中ＨＰＶ６和（或）１８型阳性率分别为５０．０％和７３．９％，两者ＨＰＶ型别分布差异有显著意义（Ｐ＜０．０１）。３例腺癌中ＨＰＶ１８型阳性２例，１６型阳性１例。低分化宫颈癌中均为ＨＰＶ１６和（或）１８型感染。提示：宫颈癌及其癌前病变的发生与ＨＰＶ感染高度相关。宫颈湿疣和ＣＩＮ＿（１～２）常与ＨＰＶ６Ｂ／１１型感染有关；ＣＩＮ＿３和宫颈癌的发生则与ＨＰＶ１６、１８型关系密切。     

尖锐湿疣及子宫颈癌组织人乳头状瘤病毒DNA的比较研究

目的：探讨不同种类人乳头状瘤病毒（ＨＰＶ）感染与病变性质的关系。方法：采用聚合酶链反应和Ｓｏｕｔｈｅｒｎ杂交方法，检测尖锐湿疣８９例（尖锐湿疣组）、宫颈癌７６例（宫颈癌组）和正常生殖道１９８例（对照组）组织标本中ＨＰＶ－ＤＮＡ，并对ＨＰＶ感染的主要类型进行分析。结果：尖锐湿疣组中，ＨＰＶ－ＤＮＡ检出率为９８．９％，ＨＰＶ６和ＨＰＶ１１占其中的８６．４％；宫颈癌组中，ＨＰＶ－ＤＮＡ检出率为９４．７％，ＨＰＶ１６和ＨＰＶ１８为主要类型，占８７．５％；对照组中ＨＰＶ隐匿感染率为３７．４％，ＨＰＶ６、１１、１６、１８仅占２１．６％。尖锐湿疣组织中ＨＰＶ１１－ＤＮＡ主要以游离形式存在，而宫颈癌组织中ＨＰＶ１６－ＤＮＡ绝大多数整合到宿主细胞中，并有某种程度的变异。结论：ＨＰＶ的不同类型与病变的组织学损害所表现的特殊形态及性质改变有关。ＨＰＶ－ＤＮＡ与宿主细胞ＤＮＡ的关系及其变异情况，可确定疾病的性质。     

子宫颈鳞癌组织中人乳头状瘤病毒E7蛋白与Rb基因产物的关系

目的：检测子宫颈鳞癌组织中是否存在人乳头状瘤病毒（ＨＰＶ）Ｅ７蛋白与Ｒｂ基因产物（ｐＲｂ）的结合物（ＨＰＶＥ７－ｐＲｂ）。方法：运用聚合酶链反应（ＰＣＲ）技术，对４０例宫颈鳞癌组织中ＨＰＶ６／１１、１６、１８、３３型ＤＮＡ进行检测，并用捕获酶联免疫吸附试验，探查ＨＰＶ感染的标本中有否ＨＰＶＥ７－ｐＲｂ存在。结果：４０例中，检出ＨＰＶＤＮＡ１８例（４５．０％）。１８例中９例存在ＨＰＶＥ７－ｐＲｂ，其中１例为ＨＰＶ１８，８例为ＨＰＶ１６。２例ＨＰＶ６／１１未检出ＨＰＶＥ７－ｐＲｂ。临床Ⅰ期患者ＨＰＶＥ７－ｐＲｂ的检出率高于Ⅱ～Ⅳ期患者（Ｐ＜０．０５）。ＨＰＶＥ７与ｐＲｂ的结合，与宫颈癌病理分级无关（Ｐ＞０．０５）。结论：在宫颈鳞癌组织中存在ＨＰＶＥ７－ｐＲｂ；ＨＰＶＥ７与ｐＲｂ的结合过程发生在宫颈癌变的较早阶段。     

子宫颈癌p53抑癌基因突变与病毒感染的研究

采用聚合酶链反应－单链构象多态性分析（ＰＣＲ－ＳＳＣＰ）、多重引物ＰＣＲ和巢式引物ＰＣＲ，对同一宫颈癌组织中ｐ５３基因（第６～８外显子）突变以及人乳头状瘤病毒（ＨＰＶ）和人巨细胞病毒（ＨＣＭＶ）感染进行相关性研究。并与正常宫颈组织进行对照。结果：３８例宫颈癌组中，２例有ｐ５３第７外显子突变。其中１例伴有ＨＰＶ１６感染，２例伴有ＨＣＭＶ感染。宫颈癌组ＨＰＶＩ６、１８ＤＮＡ的阳性率为６３．２％（２４／３８），ＨＣＭＶＤＮＡ为８４．２％（３２／３８）。２１例对照组中，ＨＰＶ１６、１８ＤＮＡ和ＨＣＭＶＤＮＡ的阳性率分别为４．８％和３８．１％（Ｐ＜０．００５）。ＨＰＶ１６、１８阳性的子宫颈癌中，８７．５％伴有ＨＣＭＶ感染。对照组中，无一例同时检测出ＨＰＶ１６、１８和ＨＣＭＶ者。提示：宫颈癌组织中，ｐ５３基因突变并不常见，其突变与ＨＰＶ１６、１８感染无显著关系。宫颈癌与ＨＰＶ１６、１８关系密切，ＨＣＭＶ可能与ＨＰＶ协同作用，导致宫颈癌的发生。     

应用聚合酶链反应技术测定正常子宫颈组织人乳头瘤病毒DNA的研究

应用兼并复合人乳头瘤病毒一聚合酶链反应（ＨＰＶ－ＰＣＲ）技术对１４８例外观正常的子宫颈分泌物拭子标本进行人乳头瘤病毒（ＨＰＶ）ＤＮＡ的测定。结果：正常子宫颈ＨＰＶＤＮＡ检出率为３１７６％（４７／１４８）。其中ＨＰＶ－６，１１型为６．７６％（１０／１４８）；ＨＰＶ－１６，１８型为３．３８％（５／１４８）；ＨＰＶ其它型为２１．６２％（３２／１４８）。外观正常的子宫颈，ＨＰＶ感染的主要易感年龄为２２～３４岁的青年妇女。本研究对女性生殖道ＨＰＶ感染的传播途径进行了探讨。     

徐州地区宫颈癌患者人乳头瘤病毒基因型检测分析

目的：通过对宫颈癌患者人乳头瘤病毒（ＨＰＶ）基因检测分析,了解徐州地区宫颈癌ＨＰＶ感染情况及ＨＰＶ感染与宫颈癌临床生物学行为之间的关系。方法：采用核酸分子杂交系统对１４２例宫颈癌患者行ＨＰＶ分型检测,并统计分析。结果：①１４２例宫颈癌患者中,１３６例ＨＰＶ阳性,ＨＰＶ感染率９５．７８％。其中单一感染１１７例（８６．０３％）,多重感染１９例（１３．９７％）,两者感染率差异有统计学意义（Ｐ＜０．０１）。②共检测出１３种基因型：单一感染８种,由高到低依次为ＨＰＶ１６（６６．１８％）、１８（６．６２％）、３１（５．８８％）、５８（２．２１％）、４５（２．２１％）、３３（１．４７％）、６（０．７４％）和ＣＰ８３０４（０．７４％）。而ＨＰＶ６８（２．９４％）、５２（２．２１％）、６６（１．４７％）、３９（０．７４％）、１１（０．７４％）仅出现在多重感染中。ＨＰＶ１６总感染率为７７．９４％,明显高于其他各型（Ｐ＜０．０１）。而ＨＰＶ１８总感染率７．３５％与ＨＰＶ３１、５８、３３相比差异无统计学意义（Ｐ＞０．０５）。③ＨＰＶ感染率在宫颈癌各临床分期、组织病理学分级间差异无统计学意义（Ｐ＞０．０５）。④ＨＰＶ多重感染与宫颈癌临床分期间无确定关系,但随着病理分级的加重呈降低的趋势。结论：徐州地区宫颈癌患者以ＨＰＶ单一感染为主,主要为ＨＰＶ１６,其次为ＨＰＶ１８、３１、５８;未发现多重感染增加宫颈癌的发生风险;ＨＰＶ感染不影响宫颈癌的进展及肿瘤细胞的分化。     

用光敏生物素标记的HPV6，11，16，18四型探针检测宫颈癌组织中的HPV核酸序列

本文运用分子生物学方法，制备了光敏生物素标记的人乳头瘤病毒（ＨＰＶ）６，１１，１６，１８四型探针。用原位杂交法检测了经临床诊断及病理证实为宫颈癌组织申的ＨＰＶＤＮＡ相关序列。在３３例宫颈癌组织中，有６例呈ＨＰＶ６阳性，阳性率为１８．１％；７例呈ＨＰＶ１１阳性，阳性率为２１．２％；２２例呈ＨＰＶ１６阳性，阳性年为６６．７％，１８例呈ＨＰＶ１８阳性，阳性率为５４．５％；１０例正常宫颈组织呈阴性。提示黑龙江地区宫颈癌的发生与ＨＰＶ有关，尤其是与ＨＰＶ１６，１８两型感染关系密切．特别是ＨＰＶ１８型感染率在本组中占有很高的比例。     

新疆维吾尔族妇女子宫颈癌活检组织中人类乳头状…

目的：研究我国宫颈癌高发区新疆维吾尔族妇女宫颈癌与人类乳头状瘤病毒（ＨＰＶ）感染的关系。方法：对６５便新疆维吾尔族妇女的宫颈癌活检组织标本，应用原位杂交法检测ＨＰＶ６／１１、１６／１８和３１／３３／３５ＤＮＡ；Ｌ１共有序列引物聚合酶链反应（ＰＣＲ）及Ｅ６特异型引物ＰＣＲ检测其中的５８例ＨＰＶ６、１６和１８ＤＮＡ。结果：６５例宫颈癌患者中，原位杂交法检测ＨＰＶＤＮＡ有２８例阳性（４３．１％）；Ｌ１Ｐ     

新疆维吾尔族妇女子宫颈癌活检组织中人类乳头状瘤病毒DNA的检测

目的：研究我国宫颈癌高发区新疆维吾尔族妇女宫颈癌与人类乳头状瘤病毒（ＨＰＶ）感染的关系。方法：对６５例新疆维吾尔族妇女的宫颈癌活检组织标本，应用原位杂交法检测ＨＰＶ６／１１、１６／１８和３１／３３／３５ＤＮＡ；Ｌ１共有序列引物聚合酶链反应（ＰＣＲ）及Ｅ６特异型引物ＰＣＲ检测其中的５８例ＨＰＶ６、１６和１８ＤＮＡ。结果：６５例宫颈癌患者中，原位杂交法检测ＨＰＶＤＮＡ有２８例阳性（４３．１％）；Ｌ１ＰＣＲ和Ｅ６ＰＣＲ检测ＨＰＶＤＮＡ阳性分别为１３例（２２．４％）和４５例（７７．６％）。结论：对宫颈癌标本中的ＨＰＶＤＮＡ检测，Ｅ６特异性引物ＰＣＲ敏感性最高，Ｌ１ＰＣＲ及原位杂交相对较低。新疆维吾尔族妇女宫颈癌发病与ＨＰＶ感染有密切关系。     

应用PCR技术检测宫颈人类乳头状瘤病毒感染

阴道镜下将３４例宫颈湿疣分为外生型和扁平型，用聚合酶链反应对活组织标本进行ＨＰＶ公共引物及ＨＰＶ１６、ＨＰＶ１８特异型引物检测。结果：外生型湿疣中ＨＰＶ１６、ＨＰＶ１８阳性率为１２％，扁平疣中的ＨＰＶ１６、ＨＰＶ１８阳性率达６７％（Ｐ＜００１），６４％的外生型湿疣伴外阴或阴道尖锐湿疣。提示：ＨＰＶ１６、ＨＰＶ１８阳性的宫颈扁平疣可能是宫颈癌前病变，宫颈外生型湿疣则可能是外阴阴道尖锐湿疣感染的延伸     

子宫颈癌微卫星不稳定性和HPV感染的研究

目的　探讨微卫星不稳定性 (microsatelliteinstability ,MI)及人乳头瘤病毒 (HPV)感染与宫颈癌的相关性。方法　 2 2例宫颈浸润性鳞癌石蜡标本 ,选取 3、 5、 6号染色体上的 3个微卫星位点D3S1 2 89、D5S4 0 6、D6S2 77进行MI分析 ;选用HPV 1 6 / 1 8型特异引物进行HPV检测 ;应用免疫组化法检测Ki6 7蛋白的表达。结果　在宫颈癌标本中 3个位点均未发现MI和杂合性缺失 (LOH)的改变 ;HPV1 6 / 1 8检出率为 77 3% ,Ki6 7指数明显高于对照组。结论　 3个微卫星位点未见MI和LOH的改变 ,与国外报道不同 ,可能与种族差异有关。HPV分型及Ki6 7蛋白表达的检测有助于宫颈病变的评价     

宫颈上皮内瘤变与人类白细胞抗原及人乳头瘤病毒感染相关性的研究

目的:探讨宫颈上皮内瘤变(CIN)与人乳头瘤病毒(HPV)感染及人类白细胞抗原(HLA)的相关性。方法:选取宫颈活检组织病理学诊断为CINⅠ42例、CINⅡ40例、CINⅢ29例、宫颈湿疣40例、慢性宫颈炎90例,从液基薄片检测剩余的保存液中提取宫颈脱落细胞学的基因组DNA,采用PCR方法及HLA试剂盒进行HPV16/18及HLA分型检测。结果:HPV16/18检出率CINⅠ组为21.4%,CINⅡ组为47.5%,CINⅢ组为55.2%,湿疣组为32.5%,宫颈炎组为1.1%。HLA分型表明,DR15(2)、DQ6(1)、DQ4在CIN组中阳性率分别为37.0%、44.0%、12.0%,明显高于宫颈炎组的17.5%、18.8%、3.8%(P<0.05),并且DR4阳性率随着CIN级别增高而增高(CINⅠ5.6%,CINⅡ13.9%、CINⅢ28.6%)。结论:HPV16/18感染和HLA分型与CIN及其分级密切相关,提示HLA在宫颈癌的发生、发展中可能起一定的作用。     

宫颈疾病HPV混合型感染的检测与分析

目的:探讨人乳头状瘤病毒(HPV)混合型感染导流杂交法检测宫颈疾病的价值。方法:用导流杂交法,检测本地区304例妇女(其中宫颈癌组35例、宫颈上皮内瘤变组20例、炎症组140例和正常组109例)宫颈脱落细胞21种HPV基因亚型,分析各组患者HPV多重感染的特点。结果:304例标本中检出HPV阳性94例,包括混合型30例,HPV多重感染检出率在宫颈癌组、宫颈上皮内瘤变组、炎症组和正常组分别为34.3%、20.0%、7.1%和2.8%,各组HPV混合型感染率差异有统计学意义(χ2=463.579,P<0.001);混合型感染中检出的HPV亚型由高到低依次为:HPV-16(19.2%)、HPV-52(13.7%)、HPV-58(12.3%)、HPV-18(8.2%)、HPV-11(6.8%)、HPV-6(6.8%)、HPV-31(5.5%)、HPV-33(5.5%)、HPV-66(5.5%)、HPV-39(4.1%)、HPV-53(4.1%)、HPV-68(4.1%)、HPV-56(1.4%)、HPV-59(1.4%)、CP8304(1.4%)。各疾病组检出的混合型HPV感染前3位HPV基因型均为高危型。结论:宫颈癌HPV多重感染率高,主要系高危HPV型感染所致;导流杂交法HPV混合型感染检测值得在宫颈疾病诊断中推广应用。     

HPV亚型在宫颈疾病中的分布特点

目的:探讨HPV亚型在宫颈疾病谱中,即从正常宫颈(慢性宫颈炎)、宫颈上皮内瘤变(CINⅠ、CINⅡ和CINⅢ)到宫颈癌连续发展中的分布特点。方法:回顾分析2005年6月～2008年6月在我院妇科因宫颈疾病就诊的189例患者HPV亚型检测的结果。结果:HPV总感染率56.1%(106/189),复合感染率22.6%(24/106)。正常者HPV感染率19.1%(12/63),检测到的HPV亚型主要是HPV52,58,53,16和33。CINⅠ者HPV感染率57.9%(22/38),最常见的HPV亚型是HPV52,其次是HPV58,16,33和18。CINⅡ者HPV感染率70.5%(31/44),HPV52,16,58,33和18等亚型最常见。CINⅢ者HPV感染率89.3%(25/28),HPV亚型以HPV16,52,58,31,33为主。宫颈癌患者,HPV阳性率100%(16/16),HPV16检测率最高,其次是HPV18,52,58和33。结论:宫颈疾病谱中最常见的高危型HPV亚型是HPV16。不同宫颈病变中HPV亚型感染的差异可能反映了其潜在转归能力,同时提示临床医师应关注宫颈疾病患者高危HPV亚型情况。     

Prevalence of high risk human papillomavirus types 16/18 in cytologically abnormal cervical smears in Alexandria,Egypt. A cytological and molecular study

IntroductionIn Egypt, cervical cancer ranks as the second most frequent cancer after breast cancer, among women between 15 and 44 years of age. High-risk human papillomavirus (HPV) 16 and 18 detection holds the potential to be used as a tool to detect women, at risk for consequent development of cervical cancer because of their predominance and potentially greater oncogenic nature than other high risk HPV subtypes.ObjectiveTo determine the prevalence of high-risk HPV 16/18 DNA in women with abnormal cervical cytology.Subjects and methods45 cases were collected from Egyptian women seeking routine gynecologic care. Ten cytologically normal cervical smear cell samples were included in the study as a control to be tested for the presence of HPV 16/18 DNA and were collected from asymptomatic patients having cystorectocele or coming for loop insertion or removal. The 45 specimens were subjected to real-time polymerase chain reaction, using multiplex HPV 16 and 18 PCR kit.Results45 cervical smears were collected in the present study. Cytopathological examination revealed that 5 (11.1%) were ASCUS, 8 (17.8) were LSIL, 5 (11.1%) were HSIL, 1 (2.2%) was squamous cell carcinoma (SCC), 1 (2.2%) was adenocarcinoma and 25 (55.6%) were benign (inflammatory). 20 patients with abnormal cervical cytology and 10 controls were included in the present study. In patients with abnormal cervical cytology, 5 (25%) were ASCUS, 8 (40%) were LSIL, 5 (25%) were HSIL, and 1 (5%) was SCC and 1 (5%) was adenocarcinoma. Statistical analysis revealed a significant difference between patient and control groups as regards regularity of menstruation where irregular menstruation and higher prevalence of menopausal women, abnormal vaginal bleeding, menorrhagia, vaginal infection, and abnormal cervical appearance were encountered in patients. A statistically significant higher prevalence of married women was found in the control group. There was no significant difference in the distribution of patients and control as regards HPV 16 or HPV 18 in which 20% of patients were HPV 16 positive and 10% of patients were HPV 18 positive compared with none in the control group. 6 were positive either for HPV 16 or 18, while 39 were negative. The HPV 16/18 positive patients had significantly higher age and marital duration when compared with HPV 16/18 negative group. Significantly, most of the HPV 16/18 positive patients were menopause. A significantly higher prevalence of women with cervicitis, contraceptive users and married women was in the HPV 16/18 negative group.ConclusionThe study generates epidemiological data of prevalence of HPV 16/18 in cytologically abnormal cervical smears in women seeking routine gynecologic care at the outpatient clinics of the Obstetrics and Gynecology Department at El Shatby University. High-risk HPV DNA testing by PCR of cervical samples diagnosed according to the Bethesda 2001 guidelines may benefit the management of patients with abnormal cervical smears, especially among women aged 46 years and older, in menopausal women and in women complaining of PMB. Therefore, HPV DNA testing should be made use of as an adjunct to cervical smears.     

组蛋白H3乙酰化和HPV感染的相关性及其对CINⅠ转归的影响

目的:探讨组蛋白H3乙酰化状态与宫颈HPV感染的相关性,及其分别与CINⅠ级转归的关系。方法:(1)选择2006年1月～2008年1月我院治疗的正常宫颈、CINⅠ、CINⅡ～Ⅲ、宫颈癌组织各30例,用免疫组化技术检测其组蛋白H3乙酰化表达水平;(2)对2006年1月～2008年1月仁济医院阴道镜下活检确诊为CINⅠ级的161例患者,用免疫组化技术检测组织中组蛋白H3乙酰化表达的水平,采用凯普技术检测宫颈HPV感染分型。结果:(1)CIN病变组组蛋白H3乙酰化水平与正常宫颈组和宫颈癌组的差异有统计学意义(P0.01)。CINⅠ和CINⅡ～Ⅲ组差异有统计学意义(P0.05);(2)组蛋白H3乙酰化表达水平增加,进展为CINⅡ级以上的发生率进行性升高,(+++)组最高达80%,差异有统计学意义(P0.05);(3)宫颈高危型HPV16/18感染的CINⅠ级,其组蛋白H3乙酰化表达水平明显高于低危型和非16/18高危型(P0.05);进展为CINⅡ级以上发生率与低危型和非16/18高危型的差异有统计学意义(P0.05);(4)不同的治疗方案对CINI级转归的影响不同,LEEP术后随访6月无1例复发,HPV转阴率77.94%(P0.05)。结论:组蛋白H3乙酰化水平和HPV感染类型与CINI级转归密切相关。     

患宫颈病变的维、汉族妇女高危型HPV分型比较研究

目的探讨人高危型乳头瘤病毒（HPV）在维吾尔族宫颈炎,宫颈癌前病变,宫颈癌中的分布及意义。方法应用Hybrimax基因芯片导流杂交技术,对2011年11月至2012年10月在新疆维吾尔自治区人民医院就诊的HC2结果阳性的428位维吾尔族及汉族妇女的宫颈细胞标本进行HPV基因型分型检测。结果 HPV16型在维吾尔族及汉族妇女在慢性宫颈炎,宫颈癌前病变和宫颈癌等不同病变比较中,差异具有统计学意义（P〈0.05）,但是两民族间的分布差异无统计学意义（P〉0.05）。HPV感染在两个民族同样是以单一感染为主,其中HPV16型单一感染最多。除HPV16、18型外,维吾尔族妇女全部宫颈脱落细胞中（宫颈炎、癌前病变及宫颈癌）常见亚型检出次数依次为HPV52、53、58、39、68,31、66、56、6和11型。汉族妇女为HPV52、58、53、31、33、68、66、39、45、11、6和CP8304型。结论 HPV16型感染是维、汉妇女正常宫颈、癌前病变及宫颈癌中常见的型别,同时随着病变进展所占比例增加,两个民族间分布差异无统计学意义（P〉0.05）;除HPV16、18型以外,高危型HPV52、58型在维、汉妇女各级别病变中最多见。维、汉妇女宫颈各病变中HPV感染以单一感染为主,两个民族妇女癌前病变及宫颈癌以HPV16型单一感染为最多见。     

子宫颈癌组织中人乳头状瘤病毒16 E6 mRNA表达与survivin蛋白表达的相关性

目的探讨宫颈癌组织中人乳头状瘤病毒(HPV)16E6mRNA表达与survivin蛋白表达的相关性。方法采用半定量PCR技术和免疫组化链霉菌抗生物素蛋白-过氧化物酶连接法,检测慢性宫颈炎、宫颈上皮内瘤变(CIN)及宫颈癌共148例患者宫颈组织中HPV16E6mRNA及survivin蛋白的表达。结果148例患者中,HPV16阳性共37例,其中慢性宫颈炎5例、CINⅠ6例、CINⅡ～Ⅲ11例及宫颈癌15例。慢性宫颈炎、CINⅠ、CINⅡ～Ⅲ及宫颈癌组织中,HPV16E6mRNA的表达水平分别为0.3±0.4、0.6±0.4、1.8±0.6及2.4±0.6;survivin蛋白阳性表达率分别为7%、31%、63%及84%。CINⅡ～Ⅲ及宫颈癌组织中,HPV16E6mRNA的表达水平及survivin蛋白阳性表达率均显著高于慢性宫颈炎及CINⅠ组织,两者比较,差异均有统计学意义(P<0.01)。宫颈癌组织中,HPV16E6mRNA的表达水平与survivin蛋白阳性表达率呈显著正相关关系(γs=0.62,P<0.05)。结论HPV16E6mRNA的表达水平与宫颈病变的进展有关,survivin蛋白阳性表达率升高可能与宫颈癌的发生、发展密切相关。     

Dominant human papillomavirus 16 infection in cervical neoplasia in young Japanese women; study of 881 outpatients

OBJECTIVE: Human papillomavirus (HPV) infection is reported to be related to carcinogenesis in the uterine cervix. In Japan, screening for cervical cancer by cytology is performed in women over 30 years old. The purpose of this study was to determine whether there is an association between patient age and cervical neoplasia or HPV infection in Japanese women. METHODS: Specimens from 881 randomly selected patients who came to our clinic were tested for HPV DNA by using Hybrid Capture II, whereas specimens from a 204-patient randomly selected subset diagnosed with cervical neoplasia were tested for HPV DNA by using polymerase chain reaction (PCR). HPV typing was performed in all the PCR-positive cases. RESULTS: The HPV-positive rate in the 20- to 29-year-old patients (29.0% in the normal cytology/histology group and 85.5% in the abnormal group) was higher than in the 30- to 59-year-old patients, and the rate declined until age 60 when age increased. While HPV 18, HPV 52, other HPV types, and HPV types as a whole were frequently detected in 30- to 49-year-old patients, HPV 16 was detected more frequently in the younger group than the other HPV types (P = 0.03). Among the HPV 16-positive patients with cervical neoplasia, the proportion of cervical intraepithelial neoplasia (CIN) 3 cases was high (44%) in the 20- to 29-year-old group. CONCLUSIONS: Screening for cervical neoplasia by cytology should also be performed in women under 30 years old in Japan. The HPV typing could be a tool to strictly follow-up younger women who were diagnosed with CIN.     

In situ hybridization study on the localization of HPV DNA in the precancerous lesions of uterine cervix

Human papillomavirus (HPV) types 16 and 18 have been found closely associated with cervical cancer. In order to investigate the relationship between HPV DNA and cervical precancerous lesions, we examined the formalin fixed specimens obtained from 22 cases of mild dysplasia, 33 cases of moderate dysplasia and 31 cases of severe dysplasia of the uterine cervix for the presence of HPV 6/11, 16 and 18 DNAs by in situ hybridization using the biotinylated HPV DNA probes. We also followed some HPV DNA positive cases of cervical dysplasia for more than 6 months prospectively. The results of in situ hybridization analysis revealed that HPV DNA was detected in the nuclei of koilocytosis, dysplastic cells and metaplastic cells. HPV 6/11 was positive in 27.3% (6/22) of mild dysplasia and 21.2% (7/33) of moderate dysplasia. On the other hand, HPV 16 positive rate increased with the grade of dysplasia and 36.4% (12/33) of moderate dysplasia, 61.3% (19/31) of severe dysplasia were positive for HPV 16 DNA. Some of the follow-up cases which were positive for HPV 16 DNA were later found to have carcinoma in situ. Our results suggest that HPV type 16 might play an important role in cervical carcinogenesis.