宫颈脱落细胞hTERC基因扩增的初步研究

目的探讨人类染色体端粒酶RNA（hTERC）基因扩增在宫颈癌发生发展中的作用及其对CIN2及以上病变筛查的临床意义。方法应用荧光原位杂交（FISH）法检测17例宫颈癌、39例CIN3、7例CIN2、14例CIN1及33例慢性宫颈炎患者宫颈脱落细胞hTERC基因扩增情况,同时对检测hTERC基因异常扩增与宫颈液基薄层细胞学检查（TCT）和高危型HPV-DNA检测诊断CIN2及以上病变的特异性和敏感性进行比较。结果 hTERC基因在慢性宫颈炎、CIN1、CIN2、CIN3及宫颈癌中的异常扩增率分别为18.19%、14.29%、35.29%、71.79%和94.12%,差异有统计学意义（χ2=41.415,P=0.000）。其中,慢性宫颈炎组和CIN1组hTERC基因扩增率比较,差异无统计学意义（P=1.000）,但均显著低于CIN2、CIN3组和宫颈癌组（P=0.001）。而且,检测宫颈脱落细胞hTERC基因扩增诊断CIN2及以上病变的敏感性为68.49%（50/73）,特异性为86.21%（50/58）,而TCT诊断CIN2及以上病变的敏感性为63.01%（46/73）,特异性为74.19%（46/62）;高危型HPV-DNA检测诊断CIN2及以上病变的敏感性为90.41%（66/73）,特异性为62.26%（66/106）。结论 hTERC基因扩增在宫颈癌的发生发展中起重要作用。FISH检测宫颈脱落细胞中hTERC基因扩增在一定程度上可反映CIN2及以上病变存在,可弥补TCT和HPV检测的不足。     

荧光原位杂交技术检测宫颈上皮内瘤变和宫颈癌细胞hTERC基因扩增的研究

目的探讨宫颈上皮内瘤变(CIN)和宫颈癌细胞涂片内人类染色体端粒酶基因(hTERC)扩增情况及其临床意义。方法2007年12月至2008年12月收集济南军区总医院107例宫颈脱落上皮标本,包括对照组20例;研究组87例,其中27例CIN(Ⅰ级8例、Ⅱ~Ⅲ级19例)和45例宫颈鳞癌(原位癌7例、Ⅰ期14例、≥Ⅱ期24例),术后2年受访15例(宫颈电热圈环切术治疗后12例,宫颈癌术后3例)。应用双色间期荧光原位杂交(FISH)技术,检测上述标本的hTERC基因扩增情况,并与液基薄层细胞检测(TCT)和病理学对照。结果(1)由对照组得出正常值为≤6.0%,>6.0%即为阳性。(2)27例CIN:Ⅰ期出现hTERC基因扩增阳性细胞百分数为9.17±4.62,阳性率为50.0%(4/8);CINⅡ~Ⅲ期为16.00±14.44,阳性率为84.2%(16/19);原位癌为19.67±13.26,阳性率为85.7%(6/7)。CIN组、原位癌组和浸润型癌组hTERC基因扩增阳性细胞百分数均显著高于对照组(P<0.01);CINⅠ期组和Ⅱ~Ⅲ组、原位癌组、Ⅰ期宫颈浸润型鳞癌组和≥Ⅱ期组之间hTERC基因扩增阳性细胞百分率递次...     

子宫颈癌及其癌前病变组织端粒酶活性的研究

目的研究宫颈癌及其癌前病变组织中端粒酶激活的意义.方法应用端粒酶重复序列扩增-酶联免疫吸附法(TRAP-ELISA)及电泳-银染法,对36例宫颈浸润癌及16例宫颈上皮内瘤变(CIN)组织进行端粒酶活性测定,以吸光度(A)值判断端粒酶活性.同时测定11例正常宫颈、6例慢性宫颈炎症及8例癌旁组织端粒酶活性作为对照.结果CIN、宫颈癌及对照组端粒酶活性A值分别为0.398±0.293、1.580±0.819和0.050±0.012,3组比较,差异有极显著性(P＜0.01).端粒酶活性高低与肿瘤分化程度呈负相关,与淋巴结转移呈正相关;与组织学类型、分期、体积大小无关.结论端粒酶的激活发生在宫颈癌病变的早期,可能成为宫颈癌及癌前病变早期诊断和鉴别诊断的指标.     

血管内皮生长因子、血管生成与宫颈癌

血管内皮生长因子（VEGF）是新发近现的一种促进血生成的糖蛋白,可促进血管内皮细胞的分化、迁移、浸润,与宫颈癌的发生、发展密切关系。本文对VEGF的结构和功能,VEGF与血管生成,CIN及宫颈癌中VEGF的表达与血管生成等方面的研究进展进行综述。     

宫颈上皮内瘤变和宫颈癌中端粒酶表达与HPV16、18感染的关系

目的探讨宫颈上皮内瘤变(CIN)和宫颈癌中端粒酶的活化与HPV16、18感染的关系.方法采用免疫组化SP法检测52例CIN和69例宫颈癌中端粒酶催化亚单位(hTERT)的表达,以原位杂交法检测HPV16、18的表达,并以18例正常宫颈组织为对照.结果正常宫颈组织中hTERT无表达,HPV16、18阳性率5.6%(1/18);CIN中hTERT阳性率50%(26/52),HPV16、18阳性率51.9%(27/52),CIN组与对照组比,两者差异均有非常显著性(P＜0.01);宫颈癌组hTERT阳性率87.0%(60/69),HPV阳性率84.1%(58/69),宫颈癌组与CIN和对照组比,两者差异均有非常显著性(P＜0.01).hTERT与宫颈癌分期、组织来源、细胞分化及有无淋巴转移等均无关.无论是CIN还是宫颈癌,hTERT阳性者HPV16、18感染率均明显高于hTERT阴性者,相比差异均有非常显著性(P＜0.01).结论端粒酶的活化与宫颈癌的发生有关,不论是CIN还是宫颈癌阶段端粒酶表达率的高低均与HPV感染率高低呈正相关关系,HPV16、18可能是端粒酶活化的始动因素.     

宫颈癌与癌前病变中高危人乳头瘤病毒型别特征及差异分析

目的:分析宫颈癌和宫颈癌前病变(宫颈上皮内瘤变Ⅱ、Ⅲ)中高危人乳头瘤病毒(HPV)型别分布特征和差异。方法:采用导流杂交技术,对432例宫颈癌和629例癌前病变进行15种高危HPV分型检测。结果:宫颈癌与癌前病变比较,HPV16型(52.08%vs 31.96%)、18型(13.66%vs6.04%)、58型(6.71%vs 16.53%)、52型(6.25%vs 13.35%)、33型(2.55%vs 5.72%)、39型(0.23%vs 1.43%),差异均有统计学意义(P0.05)。鳞癌和腺癌间比较,HPV16型(59.55%vs17.11%)、18型(10.39%vs 28.95%),差异有统计学意义(P0.05)。结论:宫颈癌和癌前病变均呈现高HPV16、18、58、52型的感染率;宫颈癌中HPV 16、18型构成比高于癌前病变,而癌前病变的HPV58、52型要高于宫颈癌;鳞癌以16型较多,腺癌则18型居多。     

宫颈癌相关肿瘤标记物的研究现状及应用前景

宫颈癌是女性最常见的恶性肿瘤之一,发病率逐年上升,并有年轻化趋势。绝大多数宫颈癌的发生发展都有较长的癌前病变阶段,但由于受到各种检测方法和经济条件的限制,多数患者发现时已为中晚期,导致病死率很高,在发展中国家尤其突出。近年研究发现,宫颈癌及癌前病变组织中存在表达异常的生物学标记物,并与前驱病变级别和肿瘤是否发生转移相关。本文较全面地综述了与宫颈癌相关的分子标记物及其在宫颈癌筛查、分类和诊断中的潜在作用,将为宫颈癌的早期诊断和预后评估提供新的思路。     

宫颈HPV感染与端粒改变及端粒酶激活的研究进展

近年 ,宫颈HPV感染呈上升趋势 ,研究表明 ,高危HPV感染与宫颈癌的发生密切相关。高危HPV转化基因E6和E7整合于宫颈细胞DNA中 ,可通过激活端粒酶 ,影响端粒而改变宿主细胞的生长模式。现就宫颈HPV感染与端粒改变及端粒酶激活研究的最新进展作一综述 ,旨在加深对HPV致癌机制的了解     

血管内皮生长因子、血管生成与宫颈癌

血管内皮生长因子(VEGF)是新近发现的一种促进血管生成的糖蛋白,可促进血管内皮细胞的分化、迁移、浸润,与宫颈癌的发生、发展有密切关系.本文对VEGF的结构和功能,VEGF与血管生成,CIN及宫颈癌中VEGF的表达与血管生成等方面的研究进展进行综述.     

高危型人乳头瘤病毒检测在宫颈癌筛查中的应用价值

目的探讨将HR-HPV检测作为宫颈癌筛查手段的意义和价值。方法2004-12-2005-04对301医院妇产科门诊就诊的1231例患者,进行HPVDNA的杂交捕获法二代(HPV-HCⅡ)和液基细胞学(Thinprepcytol-ogytest,TCT)的检测,作为宫颈癌及其癌前病变的初筛。131例因细胞学异常,或细胞学正常而HPV检测阳性,或细胞学正常HPV阴性、而临床高度怀疑病变的患者行阴道镜下多点活检,结合病理结果进行分析。结果(1)1231例样本中,经TCT检测正常者1077例(87·43%),ASCUS32例(2·60%),ASCUS-H34例(2·76),LSIL73例(5·93%),HSIL15例(1·22%)。131例阴道镜下多点组织活检,病理证实炎症68例(51·91%),CINⅠ20例(15·27%),CINⅡ18例(13·74%),CINⅢ16例(12·21%),浸润癌4例(4·35%),湿疣5例(3·82%)。(2)HPV总感染率34%,HPV阳性者418例,年龄平均(36·93±10·8)岁,HPV阴性者813例,年龄平均(39·68±11·8)岁,HPV阳性组的年龄明显小于HPV阴性组,P<0·01。各病理组HPV感染率分别为:炎症58·82%,CINⅠ80%,CINⅡ72·22%,CINⅢ100%,浸润癌100%,湿疣60%。(3)阴道镜下多点活检结果:TCT和HPV均(-)者,无高度病变的发生;TCT(-)和HPV( )者中,≥CINⅡ的检出率11·1%(1/9),TCT异常和HPV阳性同时存在的病例中,≥CINⅡ的检出率最高40·5%(32/79);仅TCT异常而HPV(-)者13·2%(5/38),且5例均为CINⅡ,无原位癌和浸润癌的发生。结论持续的HR-HPV感染与宫颈病变的演进有关;HR-HPV检测是有价值的辅助诊断技术,与细胞学联合检测,为最佳宫颈癌筛查方案。     

子宫颈上皮内瘤变端粒酶活性的研究

目的探讨端粒酶激活在宫颈癌变过程中的意义及其作为病情监测方法和预测宫颈上皮内瘤变(CIN)结局的可能性.方法采用端粒重复序列扩增-聚合酶链反应(PCR-TRAP)方法检测了64例CIN患者、21例宫颈癌患者、20例慢性宫颈炎患者及15例正常宫颈妇女宫颈脱落细胞、宫颈活组织检查(活检)组织的端粒酶活性.结果正常宫颈、慢性宫颈炎、CINⅠ级(CINⅠ)、CINⅡ级(CINⅡ)、CINⅢ级(CINⅢ)及宫颈癌患者的宫颈脱落细胞端粒酶的阳性表达率分别为20.0%、25.0%、62.5%、60.0%、82.4%及61.9%;对应的活检组织端粒酶的阳性表达率分别为26.7%、30.0%、50.0%、45.0%、96.4%及95.2%;随着宫颈病变的进展,端粒酶阳性表达率呈逐渐增高趋势(X2细胞=16.28、X2组织=36.98,P均＜0.05).CINⅠ、CINⅡ端粒酶阳性表达率比较,差异无显著性(P细胞=0.24、P组织=0.25);CINⅢ端粒酶阳性表达率高于CINⅠ、CINⅡ(P细胞=0.03、P组织=0.000012);CINⅢ与宫颈癌活检组织端粒酶阳性表达率比较,差异无显著性(P=0.05);宫颈脱落细胞与宫颈活检组织的端粒酶检测结果的对应性良好(X2=46.4,P＜0.05).结论端粒酶激活与宫颈癌变的进程有关,宫颈脱落细胞端粒酶活性检测可以作为CIN病情检测、处理及预后估计的辅助指标.     

Dicer1在宫颈肿瘤组织中的表达及意义

目的:探讨Dicer1在正常宫颈上皮、宫颈上皮内瘤变和宫颈鳞癌的表达及意义。方法:Western blot和RT-PCR法检测正常细胞系(End1/E6E7)、宫颈内瘤变细胞系(S12)及宫颈癌细胞系(Ca Ski、He La、Si Ha和C33A)中Dicer1蛋白及其mRNA表达水平,免疫组织化学技术检测Dicer1在正常宫颈、宫颈上皮内瘤变和宫颈鳞癌中的表达水平。结果:正常宫颈上皮细胞系Dicer1表达水平低于宫颈癌细胞系表达量。随着恶性程度增加,Dicer1呈驼峰状表达,即在正常宫颈组织及Grade III级宫颈鳞癌中表达较低,但在宫颈上皮内瘤变及高分化宫颈肿瘤(grade I级)中表达较高。结论:Dicer1在正常宫颈、宫颈上皮内瘤变和宫颈鳞癌中的表达有差异,为进一步研究Dicer1在宫颈癌发生发展中的作用及分子机制提供依据。     

High-grade histologic lesions in women with low-grade squamous intraepithelial lesion cytology from a region of Thailand with a high incidence of cervical cancer

Objective

To evaluate the prevalence of and predictors for underlying significant lesions in women with low-grade squamous intraepithelial lesion (LSIL) smears.

Methods

Records were retrospectively reviewed for 208 women with LSIL who underwent colposcopy and histological evaluation from October 2004 through April 2009.

Results

Mean age of the patients was 38.5 years. Forty-four (21.2%) women were nulliparous; 20 (9.6%) women were postmenopausal; 29 (13.9%) women tested positive for HIV. Thirty-three (15.9%) women were current users of combined oral contraceptive pills. The pathological results of initial colposcopic evaluations were: 63 (30.3%) with cervical intraepithelial neoplasia (CIN) 2-3; 62 (29.8%) with CIN 1; 4 (1.9%) with cervical cancer; and 79 (38.0%) with no epithelial lesion. Current use of combined oral contraceptive pills, a positive HIV test, and multiparity were significant independent predictors for high-grade disease.

Conclusion

Approximately one-third of women with LSIL in our population have underlying significant lesions. Current use of combined oral contraceptive pills, a positive HIV test, and multiparity are significant predictors for high-grade lesions.     

In situ hybridization analysis of HPV DNA in cervical precancer and cervical cancers from China

Summary A series of 103 cervical biopsies derived from 103 women during July 1958 to September 1963 from Beijing, China were investigated with in situ hybridization for the presence of HPV6, 11, 16, 18, 31 and 33 DNA. The mean age of the patients was 46.1 + 10.6 years with a range of 24–74 years. Morphological features of HPV infection were found in 80 (77.7%) biopsies. Invasive cervical cancer was diagnosed in 43 biopsies and cervical intraepithelial neoplasia CIN I, CIN II and CIN III in 9, 9, and 27 cases, respectively. A total of 63.1% (65/103) of the lesions had morphological features of HPV infections associated with CIN or invasive carcinomas. Altogether, 31.1% (32/103) of the biopsies were shown to contain HPV DNA. Of the cases showing HPV morphology, 43.1% were HPV DNA positive. HPV16 (30/32) was the most frequent type, followed by HPV11 and 18, whereas no lesions with HPV6, 31 or 33 were found. A total of 19/43 (44.2%) of the invasive carcinomas contained HPV DNA. HPV DNA positivity and the grade of CIN showed a statistically significant correlation (P=0.0011). Our study demonstrated the presence of HPV in cervical lesions among Chinese women in the late 1950's and early 1960's when a single sexual partner was the rule and also supports the concept that HPV has as an important etiological role in cervical cancer, the highest risk being associated with HPV type 16. The applicability of in situ hybridization in retrospective assessment is emphasized.     

Diagnoses and outcomes in cervical cancer screening: a population-based study

OBJECTIVE: This study was undertaken to examine routine cervical cancer screening diagnoses and outcomes on an age-specific basis in a US population. STUDY DESIGN: We conducted an observational cohort study using 1997-2002 health plan administrative and laboratory data for women enrolled at Kaiser Permanente Northwest (Portland, Ore) in 1998. RESULTS: Across all female enrollees (n=150,052), the annual rate of routine cervical cancer screening was 294.7 per 1,000, with cytologic abnormalities detected at a rate of 14.9 per 1,000. The annual incidence of cervical intraepithelial neoplasia (CIN) 1 was 1.2 per 1,000 with a rate of 1.5 per 1,000 for CIN 2/3. CIN 1 incidence peaked among women aged 20 to 24 years (5.1 per 1,000), with CIN 2/3 rates highest among those 25 to 29 years (8.1 per 1,000). From among 44,493 routine cervical smears, results were normal for 94.5%, with abnormal diagnoses of atypical squamous cells (3.3%), atypical glandular cells (0.2%), low-grade squamous intraepithelial lesion (1.2%), high-grade squamous intraepithelial lesion (0.3%), and inconclusive/inadequate (0.5%). Of women with abnormal routine smears, CIN or cancer was detected on follow-up in 19.4% of cases, 51.5% were found to have had a false-positive smear, and 29.0% incomplete follow-up as defined by published management guidelines. CONCLUSION: These are the first comprehensive age-specific estimates of routine cervical cancer screening diagnoses and outcomes to be reported within a US general healthcare setting. Overall, 5% of routinely screened women were found to have an abnormal cervical smear with an annual incidence of CIN across all female enrollees of 2.7 per 1000.     

Pregnancy outcome in patients treated with cervical conization for cervical intraepithelial neoplasia

Objective

To examine the causal contribution of conization to premature delivery.

Methods

This was a retrospective, case-control, multicenter study of women who underwent conization in 5 hospitals in the Basque Country (Spain) from 1998 to 2007. Three study groups were established: group A, post-conization infant deliveries; control group B, pre-conization infant deliveries; and control group C, infant deliveries without conization.

Results

Comparing group A with group C, there was a higher rate of preterm delivery before 35 weeks (5.3% versus 1.6%), a lower mean birth weight (3156.2 g versus 3328.5 g), and a greater prevalence of infants under 2500 g (10.6% versus 3.7%). There were no significant differences between group A and group B: preterm delivery before 35 weeks (5.3% versus 4.8%), mean birth weight (3156.2 g versus 3119.4 g), and prevalence of infants under 2500 g (10.6% versus 10.6%).

Conclusion

Pregnancy in women post-conization was associated with a risk of preterm delivery. However, there were no significant differences between women who underwent conization before and those who underwent conization after delivery. Cervical conization does not necessarily increase the risk of preterm delivery in subsequent pregnancy. Conization should be considered an indicator of such risk because it is associated with pregnancy complications arising from socio-epidemiologic factors present in women requiring conization that are also present in women who have premature delivery.     

Effectiveness of cervical cancer screening using visual inspection with acetic acid in Peru

Objective

To evaluate the effectiveness of screening using visual inspection with acetic acid (VIA).

Methods

In a low-resource area of Peru in 2005-2008, a randomly selected sample of women who had previously screened negative by VIA and Pap (intervention group), and a group of eligible women previously unscreened by VIA (comparison group) were screened by VIA. The outcome measures were histologically confirmed cervical intraepithelial neoplasia (CIN) 2-3 and invasive cervical cancer.

Results

There were 4252 women in the intervention group and 4392 in the comparison group. Histologically confirmed CIN 2 or worse was diagnosed in 31 (0.7%) and 115 (2.6%) women, and invasive cancer was diagnosed in 4 women (0.09%) and 43 women (1.00%), in the intervention and comparison groups, respectively. The adjusted odds ratio was 4.2 (95% confidence interval [CI], 2.7-6.4) for CIN 2 or worse, and 13.9 (95% CI, 4.9-39.6) for invasive cervical cancer in the comparison group.

Conclusion

A lower prevalence of CIN 2-3 and invasive cervical cancer was seen in women previously screened by VIA, as compared with women not previously screened by VIA, implying that a single VIA screening can lower the population risk for cervical cancer.     

阴道镜检查对HR-HPV阳性、细胞学阴性女性宫颈上皮内瘤变及宫颈癌筛查的意义

目的:探讨阴道镜检查对HR-HPV阳性、细胞学阴性女性宫颈上皮内瘤变(CIN)及宫颈癌筛查的意义。方法:对就诊于青岛大学附属医院的575例HR-HPV阳性、细胞学阴性妇女行阴道镜检查及宫颈活检术,分析年龄、转化区、病毒负荷量与宫颈活检病理的关系。结果:575例HR-HPV阳性、细胞学阴性的妇女中,宫颈高级别病变(CINⅡ+)的检出率为7.48%(43/575)。患者年龄为30~39岁、40~49岁、≥50岁的宫颈高级别病变患病风险分别是30岁的1.44(0.45~4.35)、0.97(0.30~3.11)、1.78(0.48~6.68)倍。不同宫颈转化区TZ1、TZ2、TZ3的CINⅡ+检出率分别为7.86%(32/407)、7.79%(6/77)和5.49%(5/91)。随着宫颈病变程度加重,病毒负荷量的中位数逐渐增加,宫颈高级别病变较低级别病变及慢性炎症的病毒负荷量较高,且差异具有统计学意义(P0.05)。结论:HR-HPV阳性、细胞学阴性女性存在一定的患宫颈高级别病变的风险,阴道镜下宫颈活检术可减少宫颈高级别病变的漏诊。病毒负荷量较高者宫颈高级别病变的患病风险较大,但患病风险与年龄无明显关系。