P21蛋白在不同级别宫颈组织中的表达及其与高危HPV感染相关性的研究

目的通过检测宫颈组织中p21waf基因表达与高危HPV感染的情况,研究P21蛋白与高危HPV感染在宫颈组织恶性转化过程中的作用及其相互关系。方法应用免疫组化检测P21蛋白及基因杂交捕获Ⅱ代技术(HC-Ⅱ)检测高危HPV在正常宫颈组、宫颈炎、宫颈上皮内瘤样病变(CIN)及宫颈癌组这4组中的表达情况。结果在正常宫颈组、宫颈炎、宫颈上皮内瘤样病变(CIN)、及宫颈癌组中P21的阳性表达率分别为11.8%、15.4%、39.1%和57.7%;高危HPV的阳性表达率分别为20%、23.5%、65.2%和88.5%,这两项指标在CIN、宫颈癌组有明显的升高趋势且与正常宫颈和宫颈炎两组相比差异具有显著性统计学意义(P<0.05);各级别宫颈组织中高危HPV阳性组的P21蛋白阳性率明显高于阴性组的P21蛋白阳性率。差异在统计学上具有显著性意义(P<0.05)。结论P21蛋白的表达和高危HPV感染与宫颈病变的恶化均有高度的相关性,其检出率和阳性表达率随着宫颈病变恶性程度的增加而升高。在CIN向宫颈癌恶性转化过程中,P21与高危HPV共同促进肿瘤的发生。     

宫颈癌中端粒酶的表达和高危型人乳头瘤病毒感染

目的:研究不同程度子宫颈病变中高危型人乳头瘤病毒HR-HPV感染和端粒酶活性的表达,以探讨两者在宫颈癌及宫颈上皮内瘤变中的作用及相关性。方法:采用第二代杂交捕获技术检测宫颈脱落细胞HPV-DNA含量,并用免疫组织化学EnVision二步法检测宫颈组织标本中端粒酶的表达。结果:(1)端粒酶阳性表达率在对照组、CINⅠ、CINⅡ、CINⅢ和宫颈癌组分别为10.00%、16.67%、40.00%、70.00%、95.00%,宫颈癌组高于CINⅢ,CINⅢ高于CINⅡ,CINⅡ高于CINⅠ,差异均有统计学意义(x2=4.329,P=0.037;x2=4.327,P=0.038;x2=4.022,P=0.045)。(2)随着宫颈病变级别的增加,高危型HPV的阳性率和病毒负荷量均增高。高危型HPV的阳性率在宫颈癌和CINⅢ组明显高于对照组、CINⅠ及CINⅡ(x2=29.501~7.414,P<0.01)。高危型HPV的病毒负荷量在对照组与其他4组比较,差异均有统计学意义(P<0.05);CINⅠ组分别与CINⅡ、CINⅢ及宫颈癌组比较差异均有统计学意义(P<0.05)。(3)随着宫颈病变级别的增加,高危型HPV的阳性率和端粒酶阳性表达率依次递增,两者有明显的相关性(r=0.943,P<0.01)。结论:高危型HPV感染和端粒酶活性均与宫颈癌前病变及宫颈癌的发生发展密切相关,有望作为子宫颈癌前病变和宫颈癌筛查的监测指标。     

高危型HPV感染对宫颈病变组织IFN-γ、IL-10表达的影响

目的:探讨高危型人乳头瘤病毒(HPV)感染对宫颈病变组织干扰素-γ(IFN-γ)、白细胞介素-10(IL-10)的影响。方法:收集我院2013年1月到2015年1月妇科门诊行宫颈活检患者150例,根据病理检查结果,将患者分为观察组(宫颈癌33例、CINⅠ期26例、CINⅡ期28例、CINⅢ期23例)110例,对照组(慢性宫颈炎患者)40例。提取两组患者宫颈组织标本,检测观察组HPV-DNA、HPV分型,及两组IFN-γ、IL-10蛋白及m RNA表达,分析高危型HPV感染与宫颈病变组织IFN-γ、IL-10表达的关系。结果:观察组HPV-DNA阳性87例(79.1%),其中HPV16型47例(42.7%)、HPV18型20例(18.2%)感染率最高;且HPV16、18感染率在CINⅠ期、CINⅡ期、CINⅢ期以及宫颈癌组中的感染率差异均有统计学意义(P0.05),Spearman相关性分析显示,HPV16、18与宫颈病变程度均呈现正相关关系(r=0.896,0.786;均P0.05)。IFN-γ、IL-10表达水平在CINⅠ期、CINⅡ期、CINⅢ期、宫颈癌、对照组表达水平差异均具有统计学意义(P0.05),Spearman相关性分析显示,IFN-γ与宫颈病变程度呈现负相关关系(r=-0.567,P0.05),IL-10呈现正相关关系(r=0.678,P0.05)。且HPV16、HPV18感染率与IFN-γ表达呈现负相关关系(r HPV16/18=-0.678,-0.675,均P0.05),与IL-10呈现正相关关系(r HPV16/18=0.582,0.778,均P0.05)。结论:IFN-γ表达随着宫颈病变加重或者HPV16、HPV18感染率升高逐渐降低,IL-10则逐渐升高。     

高级别宫颈上皮内瘤变术后转归与阴道微生态的相关性研究

目的研究高危型人乳头瘤病毒(HR-HPV)持续感染的高级别宫颈上皮内瘤变(CIN)女性行宫颈锥切术后HPV病毒感染转归与阴道微生态的相关性。方法选取2015年12月至2018年12月我院342例行宫颈锥切术的CINⅡ以上患者(术前HR-HPV检测均为阳性)为研究对象,根据术后1年随访HR-HPV感染转归分为持续阳性组58例,阴性组284例,对比两组研究对象术后1年阴道微生态检测的情况。结果持续阳性组在菌群密集度、菌群多样性及优势菌构成上与阴性组差异存在统计学意义(χ~2=13.711、37.120、25.312,P=0.001、0.001、0.001),持续感染组菌群密集度Ⅳ级构成比、菌群多样性Ⅳ级构成比均高于阴性组,优势菌为革兰阳性大杆菌低于阴性组。Nugent评分构成、pH值构成比两组差异无统计学意义(P0.05)。结论 HR-HPV的持续感染与阴道微生态平衡关系密切,在高级别CIN患者术后应注意纠正阴道微生态平衡,增强宫颈的局部免疫有利于宫颈癌的防治。     

人乳头瘤病毒感染与宫颈高级别病变关系的研究

目的探讨人乳头状瘤病毒(human papillomavirus,HPV)感染与宫颈高级别病变(highgrade squamous intraepithelial lesion,HSIL)的关系。方法选取2003年1月到2016年8月在首都医科大学附属北京天坛医院行宫腔镜辅助宫颈冷刀锥切术的患者181例,患者行宫腔镜辅助宫颈冷刀锥切术前均有HPV检测、薄层液基细胞学(TCT)以及阴道镜活检及免疫组化的结果。依据病检结果分析HPV感染与宫颈高级别病变的关系。结果在181例宫颈高级别病变中,HPV感染165例,HPV检测阳性率为91.16%。其中高危型HPV感染160例,阳性率为88.40%,占阳性标本的96.97%。HPV16阳性率57.46%,占高危型HPV感染的63.03%。40~49岁高危型HPV检测阳性率最高,但各年龄组比较差异均无统计学意义(各年龄组P值均0.05)。HPV感染在宫颈高级别病变和子宫颈癌中差异均有统计学意义(P0.05)。结论 HPV感染在宫颈高级别病变的发生和发展中起关键作用。高危型HPV基因分型诊断在宫颈癌筛查及防治过程中具有重要意义。     

人乳头瘤病毒在宫颈病变中的感染分型及其特点

目的:了解宫颈病变中人乳头瘤病毒(HPV)的感染分型及特点,为宫颈癌筛查诊治以及HPV疫苗研制提供基础。方法:采用导流杂交技术原理对2010年06月至2016年06月在广西医科大学附属肿瘤医院首诊的1021例患者的宫颈脱落细胞标本进行HPV检测,并按宫颈病变程度分为对照组(正常组)(217例)、CINⅡ-Ⅲ组(222例)和宫颈癌组(582例),分析三组的HPV感染特点和型别分布情况及其在不同年龄段(≤35岁、35岁)和民族(汉族、少数民族)中的感染特点。结果:(1)62.16%的CINⅡ-Ⅲ患者处于30-49岁,66.32%的宫颈癌患者处于40-59岁。(2)对照组、CINⅡ-Ⅲ组及宫颈癌组HPV感染率分别为20.7%、86.5%、90.5%(p0.001)。其中,多重感染率分别为11.1%、29.7%、18.0%(p0.05)。(3)CINⅡ-Ⅲ组和宫颈癌组的不同年龄段HPV感染率均高于对照组,宫颈癌组中不同年龄段的感染差异有统计学意义(p0.0001),CINⅡ-Ⅲ组差异无统计学意义(p0.05)。(4)三组HPV主要感染型别都是HPV16、58、18、52、33,但是排序先后有差异。其中,HPV33感染率在CINⅡ-Ⅲ组排第3位且主要参与多重感染,而在宫颈癌中感染率低。三组中汉族与少数民族HPV感染率差异均无统计学意义(p0.05),但宫颈癌组中少数民族患者58型感染率明显高于52型。(5)宫颈癌组病理类型与HPV感染相关,鳞癌患者的HPV感染率及多重感染率均高于非鳞癌患者,其中HPV感染差异有统计学意义(p0.05)。Logistic回归分析示:宫颈鳞癌组OR=1.966(p=0.042),95%CI值为1.023-3.775。结论:随着宫颈病变程度的增加,HPV感染增加,且多重感染与宫颈病变密切相关。HPV33可能是癌前病变特殊感染亚型,HPV58可能是少数民族特有的感染亚型。HPV感染使宫颈癌患者患鳞癌的风险增加。     

江苏妇女高危型HPV感染与宫颈癌及癌前病变相关性研究

目的:探讨江苏妇女HR-HPV基因型在正常宫颈、癌前病变(CIN I、CIN II、CIN III)和宫颈癌的分布特点及关系,为宫颈癌预防提供理论依据。方法:对2014年12月至2015年12月在我院行宫颈组织病理检查的424例江苏妇女进行HPV分型检测。以病理检查结果为依据,分为正常组、CIN I组、CIN II组、CIN III组、宫颈癌组,运用卡方检验研究江苏妇女HR-HPV感染与不同宫颈病变组的关系。结果:正常组、CIN I组、CIN II组、CIN III组、宫颈癌组的HR-HPV感染率分别为24.3%、50.0%、71.5%、75.9%、82.1%。正常组与各病变组的感染率有统计学差异(P0.01)。单一型别和多重型别感染率无差异(P=0.973);随着宫颈病变级别增加,HR-HPV分布不同。CIN I组以HPV16、52、58和51最为常见。CIN II/III组以HPV16、58、52、33和31最为常见。宫颈癌组以HPV16、53、18和58最为常见;HR-HPV感染年龄高峰为49岁,感染年龄低峰为20-29岁(P0.01)。结论:江苏妇女宫颈病变的严重程度与HR-HPV感染率呈正相关,与感染HPV高危型的数目无关。除了HPV16,HPV58、52、33和31均与宫颈癌和癌前病变密切相关。HR-HPV感染率存在年龄差异,应加强对49岁江苏女性的重视,定期进行HPV分型检测和宫颈病变筛查。     

宫颈不同疾病患者合并HPV感染的 病原菌感染状况及免疫功能

目的调查分析宫颈不同疾病患者合并人乳头瘤病毒(HPV)感染的病原菌感染状况及免疫功能。方法选择2015年3月至2018年1月在我院就诊的96例宫颈不同疾病患者为研究组,其中宫颈炎组18例,宫颈上皮内瘤变组54例(CINⅠ组15例,CINⅡ组17例,CINⅢ组22例),宫颈癌组24例;并以同期在我院进行体检的80例健康女性为对照组,检测所有研究对象的HPV感染、阴道菌群情况和宫颈分泌物CD_4~+、CD_8~+细胞数。结果研究组HPV感染率明显高于对照组(P0.05);宫颈炎组、CIN组、宫颈癌组HPV感染率呈上升趋势,组间两两比较差异均有统计学意义(Ps0.05)。宫颈炎组、CINⅠ组、CINⅡ组、CINⅢ组、宫颈癌组细菌性阴道病(BV)、解脲支原体(UU)和衣原体(CT)感染率呈上升趋势,宫颈癌组与宫颈炎组比较差异有统计学意义(P0.05);各组间人型支原体(MH)、滴虫和霉菌的感染率差异无统计学意义(P0.05)。宫颈炎组、CINⅠ组、CINⅡ组、CINⅢ组、宫颈癌组CD_4~+T细胞表达阳性率呈下降趋势,宫颈癌组与宫颈炎组、CINⅠ组比较差异有统计学意义(P0.05),CINⅢ组与宫颈炎组比较差异有统计学意义(P0.05);CD_8~+T细胞表达阳性率呈上升趋势,组间比较差异无统计学意义(P0.05);CD_4~+/CD_8~+1患者所占比例呈上升趋势,宫颈癌组、CINⅢ组、CINⅡ组与宫颈炎组比较差异有统计学意义(P0.05)。结论 HPV感染、病原菌感染及免疫功能下降与宫颈病变发生发展密切相关,临床中应给予足够重视并及时进行有效干预。     

HLA-Ⅰ表达与维吾尔族妇女宫颈癌前病变及HPV16感染的关系研究

目的:现察人白细胞相关抗原Ⅰ(human leukocyte antigen class Ⅰ, HLA-Ⅰ)表达与维吾尔族妇女宫颈癌前病变进程及高危型HPV16的关系.方法:收集维吾尔族妇女宫颈炎、宫颈内上皮瘤样病(cervical intraepithelial neoplasia, CIN)和宫颈鳞癌患者的石蜡包埋组织标本共148例,提取组织DNA,应用PCR的方法检测HPV阳性及HPV16型别;同时采用免疫组织化学SP法检测HLA-Ⅰ蛋白表达水平.结果:(1)在维吾尔族妇女中HLA-Ⅰ抗原在宫颈炎、CIN Ⅰ-Ⅱ、CIN Ⅲ、SCC组中阳性表达逐渐减少,差异有统计学意义(P<0.001).(2)HLA-Ⅰ的阳性表达下降趋势与宫颈癌临床分期、组织分化程度和淋巴结转移密切相关.(3)HPV在宫颈炎、CIN Ⅰ-Ⅱ、CIN Ⅲ、宫颈癌中的感染率分别为13%、46%、82%、95%,差异有统计学(P<0.001).(4)HPV16在宫颈炎、CIN Ⅰ-Ⅱ、CINⅢ、宫颈癌中的感染率分别为4%、30%、68%、85%,差异有统计学(P<0.001).(5)在HPV 16阳性标本中,存在HLA-Ⅰ表达缺失的占71%(58/82),HPV16感染与HLA-Ⅰ表达呈负相关(r=-0.625,P<0.001).结论:(1)HLA-Ⅰ表达缺陷可能是宫颈病变进展的重要标志,对宫颈癌的预测预警提供依据.(2)HPV16感染在宫颈病变的发展过程中起到了极大的促进作用,是一个很强的致癌因素.(3)HPV16感染与HLA-Ⅰ表达之间的关系对揭示宫颈癌发病机制提供了客观依据.     

高危型HPV 感染对宫颈病变组织IFN-r、IL-10表达的影响

目的：探讨高危型人乳头瘤病毒（HPV）感染对宫颈病变组织干扰素-r(IFN-r)、白细胞介素-10(IL-10)的影响。方法：收集我 院2013 年1 月到2015 年1 月妇科门诊行宫颈活检患者150 例,根据病理检查结果,将患者分为观察组（宫颈癌33 例、CINⅠ期 26 例、CINⅡ期28 例、CINⅢ期23 例）110 例,对照组（慢性宫颈炎患者）40 例。提取两组患者宫颈组织标本,检测观察组 HPV-DNA、HPV 分型,及两组IFN-r、IL-10 蛋白及mRNA 表达,分析高危型HPV感染与宫颈病变组织IFN-r、IL-10 表达的关系。 结果：观察组HPV-DNA阳性87 例（79.1%）,其中HPV16 型47 例（42.7%）、HPV18 型20 例（18.2%）感染率最高;且HPV16、18 感 染率在CINⅠ期、CINⅡ期、CINⅢ期以及宫颈癌组中的感染率差异均有统计学意义（P<0.05）,Spearman相关性分析显示,HPV16、 18 与宫颈病变程度均呈现正相关关系（r=0.896,0.786;均P<0.05）。IFN-r、IL-10 表达水平在CINⅠ期、CINⅡ期、CINⅢ期、宫颈 癌、对照组表达水平差异均具有统计学意义（P<0.05）,Spearman 相关性分析显示,IFN-r与宫颈病变程度呈现负相关关系（r=-0. 567,P<0.05）,IL-10 呈现正相关关系（r=0.678,P<0.05）。且HPV16、HPV18 感染率与IFN-r表达呈现负相关关系（rHPV16/18=-0. 678,-0.675,均P<0.05）,与IL-10 呈现正相关关系（rHPV16/18=0.582,0.778,均P<0.05）。结论：IFN-r表达随着宫颈病变加重或者 HPV16、HPV18 感染率升高逐渐降低,IL-10 则逐渐升高。     

安康地区人乳头瘤病毒感染特征及其与宫颈癌的关系研究

目的:调查安康地区女性人乳头瘤病毒(HPV)感染的基因型别及年龄分布特征,分析其与宫颈癌的关系,为宫颈癌防治及HPV疫苗研发提供可靠的依据。方法:收集2010年6月-2012年8月间在本院及安康市部分县级医院妇产科就诊的2736名女性的液基细胞学和组织学标本,分为8个年龄组:16-24岁119例、25-29岁230例、30-34岁343例、35-39岁472例、40-44岁574例、45-49岁512例、50-54岁206例、55-86岁280例,进行病理学分类及HPV分型检测,分析不同年龄组及不同类型宫颈组织中的HPV感染率。结果:2736例女性中发生HPV感染720例(26.32%),共检出21种型别,感染率最高的基因型别是HPV16(25.05%),其他常见型别依次为HPV58、HPV52、HPV6、HPV11。单一感染占76.25%,多重感染占23.75%。HPV感染率在16-24岁、35-39岁和55-86岁三个年龄段出现高峰;而高危型HPV的感染率在35-39岁和55-86岁两个年龄段分别出现高峰。HPV的检出率随着宫颈病变的严重程度而增加,其中正常或炎症人群的HPV感染率显著低于宫颈病变及宫颈鳞状细胞癌患者(均P0.05),且意义未明的不典型鳞状细胞(ASCUS)、CIN1-3及宫颈鳞状细胞癌患者的HPV感染率对比结果存在显著差异(P0.05)。CIN1组、CIN2-CIN3组及宫颈鳞状细胞癌组单一感染率逐渐增加(P0.05),且其二重、三重感染率比较差异均有统计学意义(P0.05)。结论:安康地区HPV16型别感染较广,临床需加强对HPV16型单一感染宫颈病变患者的癌症预防工作。     

Screening For High- and Low-Risk Human Papillomavirus Types In Single Routine Cervical Smears By Non-Isotopic In Situ Hybridization

Routine cervical smears (n = 262) from a Sexually Transmitted Diseases clinic were screened by non-isotopic in situ hybridization (NISH) stratifying human papillomavirus (HPV) infections into HPV6/11 (low risk) and HPV16/18/33 (high risk) categories. Of 188 patients with cytologically normal smears, HPV sequences were demonstrated in 41%. Of the 128 cases analysed by dual NISH, 16% contained low risk, 20% high risk and 5% both groups. In patients with cytological evidence of wart virus infection (WVI) only, 54% (n = 50) contained high-risk and 22% low-risk HPV types. The comparable incidences in CIN1/2 plus WVI (n = 24) were not significantly different: 54% and 17%, respectively. Cytological criteria underestimate the prevalence of HPV infection in patients with cytologically normal smears. This represents either 'occult' or 'latent' infection. The identical prevalence of HPVB16/18/33 in WVI only, and CIN1/2 plus WVI, suggests that the cytopathic effect induced by these HPVs may represent one end of a spectrum of morphological change which progresses to cervical intraepithelial neoplasia (CIN).     

高危HPV 感染及hTERC 基因在宫颈癌发生发展中的相关性

目的:探讨高危人乳头瘤病毒及人类染色体端粒酶基因(hTERC)在宫颈癌发生发展中的关系。方法:2010年10月至2011年05月就诊于哈尔滨医科大学附属第一医院妇科患者445例,采用表面等离子体谐振法(SPR)及荧光原位杂交法(FISH)分别检测高危HPV和hTERC的表达情况,对任一结果阳性者行阴道镜下宫颈活检和病理学检查,其中炎症对照组45例,CIN组33例及宫颈癌组6例。结果:单一型HPV29例,多重型26例,最常见为HPV16型合并的二型感染(17例)。在炎症组,CINⅠ组,CINⅡ组、CINⅢ组及宫颈癌组中多重高危HPV比率为17.78%、28.57%、44.44%、50.00%、66.67%,与炎症对照组比较其他组均有统计学意义(P<0.05)。hTERC基因在各组中的阳性表达率分别为2.22%、14.29%、61.11%、75.00%及100%。CIN组及宫颈癌的hTERC基因表达与炎症组比较差异均有统计学意义(P均<0.01),其中CINⅡ及以上各组差异明显。多重HPV感染与hTERC表达呈中等正相关(r=0.462,P<0.01)。结论:随着宫颈病理类型分级升高,HPV感染及hTERC基因表达率升高,hTERC基因在宫颈癌发生发展中起重要作用;高危HPV感染与hTERC基因的异常扩增关系密切,提示二者可能存在因果关系。     

Prevalence of HPV 16 and HPV 18 Lineages in Galicia,Spain

Genetic variants of human papillomavirus types 16 and 18 (HPV16/18) could differ in their cancer risk. We studied the prevalence and association with high-grade cervical lesions of different HPV16/18 variant lineages in a case-control study including 217 cases (cervical intraepithelial neoplasia grade 2 or grade 3 or worse: CIN2 or CIN3+) and 116 controls (no CIN2 or CIN3+ in two-year follow-up). HPV lineages were determined by sequencing the long control region (LCR) and the E6 gene. Phylogenetic analysis of HPV16 confirmed that isolates clustered into previously described lineages: A (260, 87.5%), B (4, 1.3%), C (8, 2.7%), and D (25, 8.4%). Lineage D/lineage A strains were, respectively, detected in 4/82 control patients, 19/126 CIN3+ cases (OR = 3.1, 95%CI: 1.0–12.9, p = 0.04), 6/1 glandular high-grade lesions (OR = 123, 95%CI: 9.7–5713.6, p<0.0001), and 4/5 invasive lesions (OR = 16.4, 95%CI: 2.2–113.7, p = 0.002). HPV18 clustered in lineages A (32, 88.9%) and B (4, 11.1%). Lineage B/lineage A strains were respectively detected in 1/23 control patients and 2/5 CIN3+ cases (OR = 9.2, 95%CI: 0.4–565.4, p = 0.12). In conclusion, lineages A of HPV16/18 were predominant in Spain. Lineage D of HPV16 was associated with increased risk for CIN3+, glandular high-grade lesions, and invasive lesions compared with lineage A. Lineage B of HPV18 may be associated with increased risk for CIN3+ compared with lineage A, but the association was not significant. Large well-designed studies are needed before the application of HPV lineage detection in clinical settings.     

宫颈HPV16持续感染阶段宫颈P16和Ki67的表达及其与宫颈癌变的关系

目的:探讨宫颈人乳头状瘤病毒(HPV)16持续感染阶段宫颈P16和Ki67的表达及其与宫颈癌变的相关性。方法:采用P16/Ki67免疫组化双染法检测102例HPV16持续感染者、136例非持续感染者宫颈组织P16、Ki67蛋白的表达,并根据免疫组化结果分组为双染阳性组、双染阴性组。所有患者随访观察2年,比较两组患者的结局及宫颈癌前病变的发生率。结果:P16、Ki67及P16/Ki67双染的阳性率分别为40.3%、44.5%及34.0%,HPV16持续感染患者P16、Ki67及P16/Ki67双染的阳性率均显著高于非持续感染患者(P0.05)。HPV16持续感染患者的P16、Ki67蛋白表达呈显著正相关(P0.05)。HPV16持续感染患者中,双染阳性组的病情持续和进展比例明显高于双染阴性组,也明显高于HPV16非持续感染(双染阴性组、双染阳性组)患者(P0.05)。HPV16持续感染患者中,双染阳性组进展为HSIL及以上病变发生率为32.5%(13/40),显著高于双染阴性组6.5%(P0.05)。结论:P16,Ki67双染阳性在HPV16持续感染阶段与宫颈上皮内病变疾病进展成正相关,对HPV16持续感染进展为宫颈高度病变有预警价值,可作为HPV16阳性早期治疗的敏感指标。     

Human papillomavirus in invasive cervical cancer and cervical intraepithelial neoplasia 2 and 3 in Venezuela: A cross-sectional study

BackgroundThis study investigated the distribution of human papillomavirus (HPV) types in invasive cervical cancer (ICC), cervical intraepithelial neoplasia 2 (CIN2) and cervical intraepithelial neoplasia 3 (CIN3) in Venezuela.MethodsParaffin-embedded samples from 329 women from 29 medical centers of the 24 states of Venezuela were analyzed to determine the distribution of HPV types for ICC, CIN2, and CIN3, the prevalence of single and multiple infection, and the association of HPV types with severity of lesion, comparing CIN2 versus CIN3+ (CIN3 and ICC). The samples were analyzed with the polymerase chain reaction (PCR) followed by reverse hybridization for the identification of HPV types.ResultsHPV was identified in 95/96 ICC specimens (98.9%), in 142/149 CIN3 (95.3%) and in 78/84 CIN2 samples (92.8%). The most common types for ICC and CIN3 were: HPV16, 18, 31, and 33, and for CIN2 were HPV16, 31, 51, 52, and 18. HPV single infection was found in 82.1% of ICC cases, in 79.4% of CIN2 cases, and in 77.4% of CIN3 cases. HPV16 was identified as a single infection more frequently in women with CIN3+ than in those with CIN2 (68.6% versus 46.7%, P = 0.002), and HPV16 or HPV18 types were more prevalent in CIN3+ than in CIN2 (73.4% versus 50%, P = 0.0006).Conclusionthis is the first study of the distribution of HPV types in ICC, CIN2, and CIN3 conducted throughout the territory of Venezuela. HPV16 and HPV18 were the most frequent HPV types identified in single and multiple infections in both ICC and CIN3 groups, and are associated with severity of lesion. The knowledge of the distribution of HPV types would allow organization of an HPV-DNA-based screening test, and consideration of the implementation of prophylactic vaccination in Venezuela.     

Long-Term Follow-Up of HPV16-Positive Women: Persistence of the Same Genetic Variant and Low Prevalence of Variant Co-Infections

HPV16 variants correlate with geographic origin and ethnicity. The association between infection with a specific variant and the cervical disease risk remains unclear. We studied the prevalence, persistence and association with cervical intraepithelial neoplasia (CIN) of different HPV16 variants, using cervical swabs and whole tissue sections (WTS) of biopsies from 548 women in the placebo group of a HPV16/18 vaccine trial. In HPV16-positive samples, HPV16 variants were identified by a reverse hybridization assay (RHA). Laser-capture micro-dissection (LCM) was performed for localized detection of HPV. HPV16 variants were determined in 47 women. Frequency of mixed HPV16 variant infections was lower (8.5%) than for multiple HPV genotypes (39.1%). Among 35 women having consecutive HPV16 variant-positive swabs, 32 (91.4%) had the same variant while in three (8.6%) women a change in variant(s) was observed. HPV16-positive WTS were obtained from 12 women having consecutive HPV16 variant-positive swabs. The same variant was present in WTS of 10 women, while two were negative. WTS of five women were histologically normal. A single HPV16 variant was detected in four women having CIN1-3, while additional HPV genotypes were found in three other women having CIN2 and CIN3. In the WTS of one woman with mixed genotypes, the HPV16 variant was assigned to a CIN2 lesion by LCM. HPV16 variant infections can be effectively studied in cervical swabs and tissue specimens by the HPV16 variant RHA. Multiple HPV16 variants in one woman are rare. The HPV16 genotype consistently detected in follow-up samples usually involves a persistent infection with the same variant.     

宫颈环形电切及锥切术治疗子宫颈病变临床分析

目的探讨宫颈环形电切及锥切术（LEEP）在宫颈上皮内瘤变（CIN）等宫颈病变诊疗中的应用价值。方法对我院以LEEP治疗CIN等宫颈病变69例,对比手术前后病理检查结果、并进行随访,统计其HPV感染情况。结果术前宫颈活检与术后病理检查结果符合率为76．8％（53／69）。LEEP可以一次性治疗CINⅠ和反复宫颈炎病例,在41例CINⅡ和Ⅲ病例中有2例复发。HPV感染率在CIN中70．0％（42／60）,反复宫颈炎患者中44．4％（4／9）。结论LEEP治疗CIN等宫颈病变手术操作简便,术后恢复好、复发率低,是可以推广的较为理想的诊断及治疗措施。     

Changes in type‐specific human papillomavirus load predict progression to cervical cancer

Persistent high-risk human papillomavirus (HPV) infection is strongly associated with the development of high-grade cervical intraepithelial neoplasia or cancer (CIN3+). However, HPV infection is common and usually transient. Viral load measured at a single time-point is a poor predictor of the natural history of HPV infection. The profile of viral load evolution over time could distinguish HPV infections with carcinogenic potential from infections that regress. A case-cohort natural history study was set-up using a Belgian laboratory database processing more than 100,000 liquid cytology specimens annually. All cytology leftovers were submitted to real-time PCR testing identifying E6/E7 genes of 17 HPV types, with viral load expressed as HPV copies/cell. Samples from untreated women who developed CIN3+ (n = 138) and women with transient HPV infection (n = 601) who contributed at least three viral load measurements were studied. Only single-type HPV infections were selected. The changes in viral load over time were assessed by the linear regression slope for the productive and/or clearing phase of infection in women developing CIN3+ and women with transient infection respectively. Transient HPV infections generated similar increasing (0.21 copies/cell/day) and decreasing (−0.28 copies/cell/day) viral load slopes. In HPV infections leading to CIN3+, the viral load increased almost linearly with a slope of 0.0028 copies/cell/day. Difference in slopes between transient infections and infections leading to CIN3+ was highly significant (P < .0001). Serial type-specific viral load measurements predict the natural history of HPV infections and could be used to triage women in HPV-based cervical cancer screening.