HPV检测在宫颈病变诊断及CIN术后随访中的价值

目的:探讨宫颈脱落细胞人乳头瘤病毒(HPV)分型检测在宫颈病变诊断和宫颈上皮内瘤变(CIN)行宫颈环形电切(LEEP)术后随访中的意义。方法:选择本院因宫颈病变行宫颈病理检查的患者1280例(包括宫颈炎症870例,CINⅠ115例,CINⅡ102例,CINⅢ109例,宫颈癌84例),均采用导流杂交基因芯片技术行HPV分型检测。对其中304例行LEEP治疗后的CIN患者于术后6个月、1～2年行HPV分型检测。结果:(1)随宫颈病变程度的增高,HPV感染率、高危型HPV(HR-HPV)感染率、HPV单一感染率均呈增高趋势,而多重感染率与宫颈病变级别无关。(2)本组中304例CIN患者在我院行LEEP治疗后6个月和1～2年定期随访。术前、术后6个月、术后1～2年HR-HPV感染率(81.3%、22.4%、5.6%)逐渐降低(P<0.05)。CINⅠ、CINⅡ、CINⅢ患者术后6个月HPV感染率分别为16.8%、21.9%、28.0%(P>0.05),术后1～2年HPV感染率分别为3.0%、5.2%、8.4%(P>0.05)。(3)术后1～2年HPV阴性组、HR-HPV阳性组、低危型HPV(LR-HPV)阳性组复发率分别为0.7%(2/281)、41.2%(7/17)、16.7%(1/6)(P<0.05)。结论:HPV分型检测为早期发现和预测宫颈病变转归提供了可靠警示,可作为CIN患者LEEP术后监测预后的重要指标。     

水通道蛋白1在宫颈病变中的表达及意义

目的:检测宫颈病变组织中水通道蛋白1的表达,探讨该蛋白在宫颈癌形成和演进进程中的意义。方法:用免疫组织化学SP法检测83例石蜡包埋宫颈组织中水通道蛋白1的表达,结合临床病理分型分析其表达的意义。结果:水通道蛋白1在慢性宫颈炎、宫颈上皮内瘤样病变(CIN)和宫颈癌组织中的阳性率分别为4.0%,33.3%和74.2%,3组样本中水通道蛋白1阳性率的差异有统计学意义(P<0.05),宫颈癌病理学分级1+2级和3级相比,差异有统计学意义(P<0.01)。水通道蛋白1表达阳性率与CIN的分级,与宫颈癌临床分期、组织学分型和淋巴结转移无关(P>0.05)。结论:水通道蛋白1在宫颈癌前病变和宫颈癌组织中表达升高,可能在宫颈癌的发生发展过程中起重要作用。     

PHD2在宫颈病变中的表达及意义

目的:研究不同宫颈组织中脯氨酸羟化酶2(PHD2)的表达情况,初步探讨PHD2在宫颈病变中的作用和意义。方法:选取正常宫颈、CINⅠ和CINⅡ、CINⅢ、宫颈癌标本各20例,应用逆转录多聚酶链反应(RT-PCR)、免疫组化法(SP法)检测PHD2 mRNA和蛋白水平的相对表达情况。结果:正常宫颈、CINⅠ和CINⅡ、CINⅢ、宫颈癌组织中,PHD2蛋白和mRNA表达水平依次上调,两两比较差异均有统计学意义(P0.01)。结论:PHD2可能参与宫颈病变的发生发展,作为肿瘤标记物用于早期诊断和预后判断。下调PHD2的高表达,可能成为治疗宫颈癌的新靶点。     

半乳糖凝集素-1蛋白在宫颈病变组织中的表达及其与高危型人乳头瘤病毒的关系

目的:探讨半乳糖凝集素-1(Galectin-1)蛋白在宫颈上皮内瘤变(CIN)及宫颈癌中的表达及其与高危型人乳头瘤病毒(HR-HPV)的关系。方法:用免疫组织化学法检测宫颈癌(54例)、CINⅠ(10例)、CINⅡ(20例)、CINⅢ(25例)和正常宫颈组织(20例)中Galectin-1蛋白的表达,用第二代杂交捕获法(HC-Ⅱ)检测HR-HPV感染情况,分析Galectin-1与CIN及HR-HPV的关系。结果:Galectin-1蛋白在正常宫颈、CINⅠ、CINⅡ、CINⅢ和宫颈癌组织中的阳性表达率分别为5.0%、20.0%、40.0%、56.0%、48.1%,随着CIN病变程度的加重,Galectin-1蛋白阳性表达逐渐增强;宫颈癌和CINⅡ、CINⅢ的Galectin-1蛋白阳性表达率明显高于正常宫颈组织和CINⅠ(P<0.01),宫颈癌与CINⅡ、CINⅢ间比较、差异无统计学意义(P>0.05)。宫颈癌中Galectin-1蛋白阳性表达在有否淋巴结转移、组织学分级、临床分期和有否HR-HPV的感染中比较,差异有统计学意义(P<0.05,P<0.01),在不同组织学类型中比较,差异无统计学意义(P>0.05)。结论:Galectin-1蛋白表达增强与宫颈病变的进展有一定关系,HR-HPV可能通过诱导宫颈上皮高表达Galectin-1而促使宫颈癌发生、发展。     

宫颈脱落细胞中HPV L1壳蛋白的表达及临床意义

目的探讨HPV L1壳蛋白在宫颈脱落细胞中的表达及临床意义。方法对2010年1月至2011年10月在南京医科大学第一附属医院就诊的患者的宫颈脱落细胞标本409例用免疫细胞化学法检测HPV L1壳蛋白的表达。结果 HPV L1壳蛋白在NILM、ASCUS、ASC-H、LSIL、HSIL和AGC中的阳性表达率分别为20.54%、49.24%、18.18%、43.90%、18.18%、0%,ASCUS/LSIL组和ASC-H/HSIL组之间差异有统计学意义(P<0.05);HPVL1壳蛋白在慢性宫颈炎、CIN1、CIN2、CIN3、SCC和宫颈腺癌中的阳性表达率分别为36.11%、42.19%、30.23%、26.09%、0%、0%,CIN1组、CIN2/3组、SCC组之间差异有统计学意义(P<0.05);HPVL1壳蛋白在HR-HPV DNA负荷量0～9.9、10～99.9、100～999.9、1000～pg/ml中的阳性表达率分别为6.67%、17.24%、36.72%、51.77%,除0～9.9与10～99.9pg/ml组比较,其余各组间差异均有统计学意义(P<0.05);HPV L1壳蛋白阴性表达对高级别CIN(≥CIN2)预测的灵敏度、特异度、阳性预测值、阴性预测值分别为75.62%、37.98%、54.09%、61.72%。结论 HPV L1壳蛋白在宫颈脱落细胞中的表达率随宫颈病变程度的加重呈下降趋势,随病毒负荷量的增加呈升高趋势。     

P16和Ki-67在宫颈上皮内瘤变组织中的表达及意义

目的研究P16和Ki-67在宫颈上皮内瘤变组织中的表达及与高危型人乳头瘤病毒(HPV)的关系和临床意义。方法应用免疫组织化学方法检测2005年9月至2007年8月间广东省人民医院40例正常宫颈组织、103例宫颈上皮内瘤变(CIN)及56例宫颈浸润癌中P16和Ki-67的表达,并采用第二代杂交捕获试验(HC-Ⅱ)检测高危型HPVDNA。结果P16和Ki-67的表达强度与CIN的严重程度分别呈正相关(P<0.01)。P16和Ki-67在CINⅡ、CINⅢ、宫颈鳞癌及腺癌中表达呈阳性至强阳性的比例,明显高于正常宫颈组织及CINⅠ,差异有统计学意义(P<0.01)。高危型HPV感染阳性率88.9%(177/199),其中正常宫颈42.5%、CINⅠ87.5%、CINⅡ与CINⅢ均100%、宫颈鳞癌98.0%、腺癌60.0%。高危型HPVDNA负荷量与P16、Ki-67的表达强度分别呈正相关(P<0.01)。结论P16和Ki-67的表达强度与CIN的严重程度以及高危型HPVDNA负荷量密切相关;P16和Ki-67可作为诊断CINⅡ及CINⅢ的重要辅助指标。     

p16与宫颈病变关系的研究进展

p16是近年发现肿瘤抑制基因,其高表达与宫颈病变关系密切,且与人乳头瘤病毒(HPV)感染呈正相关.在宫颈脱落细胞中P16蛋白的表达与HC-2检测一样能够增加细胞学诊断的敏感性,且p16较HC-2检测更能够区分ASCUS细胞中是否存在病变.在一定程度上可以代替HC-2检测,提高子宫颈鳞癌的早期诊断率,从而降低传统宫颈癌筛查法的假阳性率和假阴性率,提高筛查的灵敏度和特异度,值得推广.     

p16与宫颈病变关系的研究进展

p16是近年发现肿瘤抑制基因,其高表达与宫颈病变关系密切,且与人乳头瘤病毒（HPV）感染呈正相关。在宫颈脱落细胞中P16蛋白的表达与HC-2检测一样能够增加细胞学诊断的敏感性。且p16较HC-2检测更能够区分ASCUS细胞中是否存在病变。在一定程度上可以代替HC-2检测．提高子宫颈鳞癌的早期诊断率,从而降低传统宫颈癌筛查法的假阳性率和假阴性率,提高筛查的灵敏度和特异度,值得推广。     

hTERC基因表达在宫颈病变诊治中的应用

目的：探讨宫颈脱落细胞中hTERC的基因表达在宫颈上皮内瘤样病变（CIN）诊断与治疗中的应用。方法：抽取行子宫颈癌筛查的724例妇女为研究对象,对其同步进行宫颈脱落细胞的液基细胞学检查、第二代杂交捕获技术（HC-Ⅱ）检测高危型HPV（HR-HPV）和荧光原位杂交（FISH）技术检测hTERC基因。对于细胞学为未明确诊断意义的不典型鳞状上皮细胞（ASCUS）及以上病变,和（或）HR-HPV阳性者均行阴道镜下宫颈四象限多点活检进行病理诊断。结果：724例中经病理确定为CINⅠ,Ⅱ,Ⅲ及子宫颈癌者分别为251例（34.67%）、17例（2.35%）、48例（6.63%）和10例（1.38%）,宫颈脱落细胞hTERC的扩增率为11.05%。①724例HPV阳性率为39.64%;hTERC扩增在HPV阳性与阴性组分别为19.86%与5.26%（χ2=37.556,P ＜0.01）。②hTERC扩增在细胞学无宫颈上皮内瘤变（NILM）组为5.19%、ASCUS为10.23%、低度鳞状上皮内瘤样病变为（LSIL）11.84%、非典型鳞状上皮细胞－不除外高度鳞状上皮内瘤变（ASC-H）为21.43%、高度鳞状上皮内瘤样病变（HSIL）为73.17%、鳞状细胞癌（SCCA）为100.00%、非典型腺上皮细胞（AGC）为50.00%;hTERC在HSIL及以上病变中的扩增率明显高于LSIL及以下病变（χ2=186.755,P ＜0.01）。③在不同组织学结果中hTERC的扩增率分别为,NILM 3.70%、CINⅠ4.38%、CINⅡ47.06%、CINⅢ58.33%、浸润癌90.00%,hTERC在CINⅡ及以上级别病变中的扩增率明显高于CINⅠ和NILM者 （χ2=144.597,P ＜0.01）。结论：hTERC的扩增与宫颈细胞学和组织学异常密切相关,hTERC扩增与否有可能作为判断有无高度病变及估计预后的指标之一。     

TLRs在宫颈HPV16持续性感染及宫颈病变中的作用研究

目的:探讨Toll样受体(TLRs)在宫颈人乳头瘤病毒(HPV)16持续性感染及宫颈病变中的作用。方法:以PCR法检测宫颈脱落细胞中TLR3、TLR7、TLR8、TLR9及干扰素β(IFN-β)基因在宫颈HPV16持续性感染及宫颈病变中的表达,并分为HPV16持续感染组与HPV16非持续感染组及宫颈炎症及CINⅠ组、高级别CIN和原位癌组、宫颈浸润癌组进行比较分析。结果:1在HPV16持续感染组与HPV16非持续感染组中,TLR3 DNA表达量分别为0.622±0.160、0.696±0.155,干扰素β(IFN-β)DNA表达量分别为0.640±0.169、0.735±0.151,TLR3、IFN-βDNA在HPV16持续感染组表达量低于HPV16非持续感染组(t=6.574,P=0.011;t=4.378,P=0.038);TLR3 DNA与IFN-βDNA呈正相关(r=0.693,P0.001),TLR 9DNA与IFN-βDNA呈负相关(r=-0.384,P0.001)。2在宫颈炎症及CINⅠ组、高级别CIN和原位癌组、宫颈浸润癌组中,TLR3DNA表达量分别为0.661±0.159、0.606±0.143、0.507±0.160,IFN-β表达量分别为0.722±0.169、0.659±0.144、0.483±0.143,TLR7DNA表达量为0.737±0.198、0.754±0.206、0.864±0.167,TLR9DNA表达量为0.531±0.172、0.606±0.192、0.701±0.200。TLR3、IFN-βDNA表达量随宫颈病变进展而逐渐下降(F=7.983,P0.001;F=12.163,P0.001),而TLR7、TLR9 DNA表达量则随宫颈病变进展而逐渐增高(F=3.647,P=0.028;F=9.415,P0.001)。结论:TLRs可能参与宫颈局部免疫系统对HPV16的清除过程,TLR3表达减低可能通过下调IFN-β表达而影响宫颈局部免疫功能,从而导致HPV16持续性感染。TLR3、TLR7、TLR9异常表达在宫颈病变发生及进展中可能发挥重要作用。     

Serologic response to human papillomavirus 16 among Australian women with high-grade cervical intraepithelial neoplasia

This study evaluated the detection of human papillomavirus (HPV) 16 antibody in HPV 16-associated cervical intraepithelial neoplasia (CIN) in Australian women. Seroreactivity to HPV 16 L1 virus-like particles was assessed in patients with CIN 2 (n= 169) and CIN 3 (n= 229) lesions previously tested for the presence of HPV DNA. Seropositivity was significantly commoner in women with HPV 16 DNA-positive lesions (98/184) than in women with no HPV DNA in the lesion (15/47) or with HPV of types other than 16 in the lesion (43/167) (P= 0.0004). In addition, seropositivity was observed in 33% (55/169) of women with CIN 2 and 46% (106/229) of women with CIN 3, in keeping with the lower fraction of CIN 2 (57/169) than CIN 3 (127/229) biopsies positive for HPV 16 DNA. HPV 16 seropositivity is most common in women with HPV 16-associated CIN, but many patients with HPV-associated CIN 3 are seronegative, and HPV 16 seropositivity is common in women with CIN associated with other HPV types. Overall, HPV 16 serology is a poor predictor of presence of HPV 16-associated CIN 3 in patient population studied.     

Angiogenesis in cervical intraepithelial neoplasia and early-staged uterine cervical squamous cell carcinoma: clinical significance

The objective of this study is to evaluate angiogenesis in cervical intraepithelial neoplasia (CIN), microinvasive squamous cell carcinoma (MIC), and early-staged squamous cell carcinoma (SCC), stage IB-IIA of the cervix. Microvessel density (MVD) was evaluated and correlated with other pathologic prognostic factors and disease outcomes. Four hundred seventy-four cervical specimens were studied. Among these, 100 were designated normal cervix, 30 CIN1, 32 CIN2, 178 CIN3, 74 MIC, and 60 early-staged SCC. MVD per high-power field (x400) of early-staged SCC, MIC, and CIN3 were significantly higher in comparison to CIN2, CIN1, and control subjects (P<0.05). There was no statistically significant difference in MVD between control group, CIN1, and CIN2. In early-staged SCC, no correlation between MVD and pelvic lymph node status, parametrial involvement, depth of stromal invasion, and lymphovascular space invasion was found. Patients with bad outcomes (recurrence or death) showed no statistically different MVD from the ones who had unremarkable clinical courses.     

微型染色体维持蛋白7在宫颈癌早期诊断和预防中的价值

目的探讨微型染色体维持蛋白7(MCM7)在宫颈癌早期诊断和预防中的意义。方法 2008年1月至2009年10月在皖南医学院附属弋矶山医院就诊的宫颈上皮内瘤变(CIN)1、2、3和宫颈癌患者各40例,慢性宫颈炎20例为对照。采用免疫组化法测定MCM7、细胞周期蛋白E(Cyclin E)、Ki-67在各组中的表达,同时检测人乳头瘤病毒(HPV)DNA分型。结果 MCM7在各组中的阳性表达率均为100%,各组间比较,差异有统计学意义(P<0.001)。宫颈癌与CIN3比较,差异无统计学意义(P>0.05);与其他组比较,差异有统计学意义(P均<0.001)。在各组中,高危型HPV阳性率均≤92.5%。在宫颈癌和CIN3中,MCM7的表达水平高于Ki-67和Cyc-lin E,差异具有显著性(P均<0.001)。结论 MCM7可能是早期诊断和预防宫颈癌的理想标志物。     

Colposcopy and cervical intraepithelial neoplasia

Cervical cancer is both preventable and curable. It has a long natural history with a prolonged pre-cancerous phase that is easily detectable and treatable. Exfoliative cytology has been the mainstay for screening of cervical intra-epithelial neoplasia (CIN). Assessment of women presenting with abnormal cervical cytology and the selection of those requiring treatment relied mainly on colposcopic impressions of the cervical transformation zone and the histological appraisal of directed punch biopsies. The need to maximise clinical resources, achieve quicker and more effective management of patients, limit postoperative complications and preserve reproductive function has led to the popularity of local excisional methods for cervical premalignancy. Although the cure rates for all local ablative and excisional methods are more than 90% after one treatment, the excisional methods provide a more reliable histopathological diagnosis and the patient can be treated at the initial visit. The recognition that persistent infection with oncogenic human papillomavirus (HPV) causes cervical cancer has led to the development of new HPV tests/biomarkers and prophylactic vaccines against HPV. The HPV DNA test that targets the viral DNA has been introduced as a test of cure after CIN treatment and as a triage tool in women presenting with borderline or low-grade findings at cytology. HPV DNA test will be introduced in primary screening in the future. The national HPV immunisation programme was initiated in the NHS in September 2008. The vaccines are safe, well tolerated and highly efficacious in HPV naive women.     

COX-2和VEGF在宫颈癌组织中的表达及其生物学意义

目的　探讨环氧化酶 2 (COX - 2 )和血管内皮生长因子 (VEGF)在宫颈癌中的表达及其与宫颈癌临床病理特征的关系。方法　采用免疫组化SP法检测COX - 2、VEGF在 6 8例宫颈癌、 14例正常宫颈组织中的表达。结果　COX - 2和VEGF蛋白在宫颈癌和正常宫颈组织中的表达差异有显著性 (P <0 0 1)。COX - 2蛋白表达与宫颈癌分化程度、组织学类型、淋巴结转移等显著相关 (P <0 0 5 ) ;VEGF蛋白表达与宫颈癌临床分期、淋巴结转移有显著相关 (P <0 0 5 )。宫颈癌中VEGF与COX - 2的表达密切相关。结论　COX - 2和VEGF 2种蛋白与宫颈癌的发生发展相关 ,并在宫颈癌的侵袭转移中起一定作用。     

Cytokine profile in Indian women with cervical intraepithelial neoplasia and cancer cervix

Cervical cancer develops from the preneoplastic cervical intraepithelial neoplasia (CIN). Host factors are critical in regulating tumor growth and cytokines, which modulate immunologic control may be of particular importance. The objective of this study was to assess the production of cytokines by peripheral blood mononuclear cells (PBMCs) in Indian women with cancer cervix and CIN. Sixty patients with cancer cervix (including all FIGO stage I-IV), 35 patients with CIN, and 30 healthy controls were enrolled in this study. The human papillomavirus (HPV) 16 and 18 status was determined in all the study groups. The PBMC culture supernatant was collected for cytokine estimations by enzyme-linked immunosorbent assay (interleukin-2 [IL-2], interferon-gamma [IFN-gamma], interleukin-4 [IL-4], and interleukin-10 [IL-10]). IL-2 levels showed a significant decline in high-grade CIN and cancer patients, whereas IFN-gamma levels were decreased only in patients with advanced cancer cervix. An increase in the levels of IL-4 and IL-10 was found in all cancer cervix and CIN grade III patients, as compared to those with early CIN grades and healthy controls. The cytokine ratios decreased significantly (P < 0.001 for all the ratios), when cervical cancer patients were compared with controls and CIN cases. The type 2 and type 1 cytokine levels were significantly correlated (P < 0.000) with HPV status. We conclude that a pronounced shift from type 1 to type 2 cytokine production is associated with more severe disease. These data reinforce the need for detailed analysis of immune dysregulation in CIN and cancer cervix patients.     

红色诺卡氏菌细胞壁骨架治疗子宫颈高级别鳞状上皮内病变的安全性和疗效研究

目的 探讨子宫颈外用红色诺卡氏菌细胞壁骨架(Nocardia rubra cell wallskeleton,Nr-CWS)治疗子宫颈高级别鳞状上皮内病变(HSIL)的安全性、耐受性和有效性.方法 选取2017年4月至2018年3月在北京大学第一医院妇产科宫颈中心就诊的子宫颈HSIL患者,回顾性分析子宫颈环形电切除术(...     

CD1a和E-cadherin在宫颈上皮内瘤变中的表达

目的:探讨CD1a和E-cadherin与宫颈癌发生发展的关系及作为早期癌变生物学指标的可能性。方法:采用免疫组化SP法检测CD1a和E-cadherin在同期56例宫颈上皮内瘤变、56例宫颈鳞癌和15例正常宫颈组织中的分布及表达。结果:(1)CD1a+朗格汉斯细胞在正常宫颈、CIN和宫颈癌各组中数量逐渐减少,两两比较有显著差异(P0.01);CIN中该细胞数量随病变严重程度减少,CINⅠ和CINⅡ、CINⅠ和CINⅢ组之间两两比较有显著差异(P0.05),而CINⅡ与CINⅢ组间无显著差异(P0.05);(2)E-cadher-in在正常宫颈、CIN和宫颈癌各组中的阳性表达率及强度逐渐下降,两两比较有显著差异(P0.05);在CIN中阳性表达率及表达强度随病变严重程度呈下降趋势,CINⅠ和CINⅡ、CINⅠ和CINⅢ之间两两比较有显著差异(P0.05),而CINⅡ和CINⅢ之间无显著差异(P0.05);(3)宫颈组织中CD1a+朗格汉斯细胞的细胞数与E-cadherin的阳性表达率及强度呈正相关(r=0.912,P0.05)。结论:CD1a+朗格汉斯细胞与E-cadherin可能在宫颈癌的发生、发展过程中起重要作用。