宫颈鳞状上皮内瘤变二级命名法的临床应用

目的探讨2013年WHO关于宫颈鳞状上皮内瘤变二级命名法的临床应用及相关问题。方法采用免疫组化技术检测p16、Ki-67蛋白在111例宫颈良性反应性病变（良性病变组）、81例CIN1、39例CIN2患者组织中的表达情况。并分析宫颈低级别及高级别鳞状上皮内瘤变二级命名法中,不同级别病变与p16、Ki-67蛋白表达的关系。结果 p16在良性病变、CIN1和CIN2组中的阳性表达率分别为18.92%、41.98%和64.10%,良性病变组与CIN1、CIN2组比较,差异均有统计学意义（P〈0.05）;Ki-67在良性病变、CIN1和CIN2组中的阳性表达率分别为32.43%、32.10%和69.23%,CIN2组与CIN1组、良性病变组比较,差异均有统计学意义（P均〈0.05）。p16和Ki-67蛋白联合检测：在良性病变、CIN1、CIN2组中,p16（＋）/Ki-67（＋）的表达率分别为11.71%、9.88%和43.59%,p16（＋）/Ki-67（-）的表达率分别为7.21%、32.10%和20.51%;p16（-）/Ki-67（＋）的表达率分别为20.72%、22.22%和25.64%;p16（-）/Ki-67（-）的表达率分别为60.36%、35.80%和10.26%。三组中p16阴性着色特点不同,Ki-67的阳性着色特点不同。结论 p16蛋白联合Ki-67可以很好地区分低级别和高级别宫颈鳞状上皮内瘤变,但其有赖于免疫组化判读标准的严格执行;同一级别不同的染色特点可能代表组织的不同生物学特性,但尚需大量的临床验证。     

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。     

阴道镜对宫颈上皮内瘤变的诊断价值

目的：评价阴道镜检查对宫颈上皮内瘤样病变（CIN）的诊断价值。方法：对1991年5月至2002年4月进行阴道镜检查的患者1407例，行镜下定位取活组织病理检查。结果：近4年来CIN的发病例数呈上升趋势，发病年龄在30－39岁的病例占80．29％，经病理确诊CIN406例，包括CIN Ⅰ209例，CINⅡ104例和CINⅢ（包括CIS）93例；慢性宫颈炎625例，湿疣187例，息肉139例，其他50例（包括宫颈纳氏囊肿28例，子宫内膜异位症13例，乳头状瘤9例），阴道镜检查对CIN的诊断准确性为79．67％，敏感性为96．06％，特异性为73．03％，阳性预测值为59．095，阴性预测值为97．86％。CIN在阴道镜下的图像以醋酸白色上皮的出现率最高为83．50％，对CIN诊断的敏感性和阴性预测值高；与点状区和（或）镶嵌同时存在时，对CIN诊断的敏感性下降，特异性升高，结论：阴道镜检查对CIN的诊断价值在于其敏感性和阴性预测值高，在国内适合作为CIN的筛查方法，统一阴道镜的评分标准意义重大。     

阴道镜下常规活检诊断宫颈上皮内瘤样病变108例分析

目的：通过阴道镜下常规活检，探讨宫颈上皮内瘤样癌变（CIN）的检查率、镜图像特征及诊断价值。方法：回顾分析5年来阴道镜检查834例中108例CIN的阴道镜检结果。结果：834例中CIN发现108例，占12．8％，CIN的异常阴道镜像主要为血管异常及腺口白环、白腺。结论：阴道镜是辅助诊断CIN的重要方法，初次阴道镜检可疑时应进行常规活检。     

宫颈上皮内瘤样病变临床诊断方法的分析

目的　探讨宫颈细胞学、阴道镜和宫颈活检联合检测对宫颈病变的诊断价值。方法　对宫颈细胞学异常 ,进行阴道镜检查及镜下多点活组织病理检查 195例患者的临床资料进行回顾性分析。结果　电脑辅助细胞学检测系统 (CCT)检查共 195例。未明确诊断意义的不典型磷状上皮细胞 (ASCUS) 90例中 ,宫颈活检病理为炎症 2 6例 (30 % ) ;CIN 6 3例 (70 % ) ,其中 ,CINⅠ 5 2例 (5 7 78% ) ,合并人乳头状瘤病毒 (HPV)感染14例 (15 5 6 % ) ;CINⅡ 6例 (6 6 7% ) ;宫颈上皮内瘤样病变 (CIN)Ⅲ 5例 (5 5 6 % )。细胞学诊断低度磷状上皮内瘤变 (LSIL) 71例 ,其中 17例 (2 3 94 % )为炎症 ,符合低度病变为 4 5例 (6 3 38% ) ,高度病变为 9例(12 6 8% ) ,LSIL合并HPV感染 2 4例 (33 8% ) ,病理检查合并HPV感染 2 4例 (33 8% )。细胞学诊断高度磷状上皮内瘤变 (HSIL) 2 8例 ,其中低度病变为 8例 (2 8 5 7% ) ,符合高度病变为 18例 (5 7 14 % )。微小浸润癌 1例(3 5 7% )。结论　细胞学筛查异常者 ,应结合阴道镜下多点活检进一步诊断 ,有利于提高CIN的检出率。有性生活的妇女应定期进行细胞学筛查或阴道镜检查     

微波治疗子宫颈上皮内瘤样变

对１９９０年１１月至１９９３年１２月就诊于我院妇产科门诊经阴道镜和病理组织学确诊为子宫颈上皮内瘤样变（ＣＩＮ）１，２级的病例１２８全，地微波治疗（微波组，４３例）、电灼治疗（电灼组，３９例）和ＣＯ２激光治疗（激光组，４６例）。治疗深度为子宫颈口深１．０ｃｍ，治疗范围超出病变外０．３ｃｍ，创面呈锥形。     

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.     

子宫颈上皮癌变过程中Ki67表达和HPV感染的研究

目的 研究Ki67表达和HPV感染在宫颈癌发生发展过程中的意义。方法 分别从正常宫颈(10例)、各级CIN(CIN Ⅰ19例,CIN Ⅱ9例,CIN Ⅲ16例)和宫颈鳞癌(8例)的石蜡标本提取基因组DNA,选取HPV L1区通用引物进行PCR扩增,测序,与已知HPV序列进行同源性分析。Ki67免疫组化染色。结果 正常宫颈组HPV DNA均为阴性。CIN Ⅰ组5/19例为高危型HPV(16/18型),8/19例为中危型(35型等),其余为低危型。CINⅡ和Ⅲ组高危和中危型HPV各占一半。宫颈癌组均为高危型,绝大部分为HPV16。Ki67指数随CIN级别的升高(CINⅠ:21.4±1.1,CINⅡ:31.8±3.5 CINⅢ:61.3±2.8)而明显增加(P<0.01)。结论Ki67指数反映出在宫颈上皮细胞癌变过程中细胞增殖活性的改变。HPV型别与CIN级别及转归密切相关。Ki67与HPV检查联合应用对评价CIN细胞增殖活性及其转归有重要的作用,对伴有HPV16/18 感染的CIN应密切追踪和积极处理。     

宫颈上皮内瘤样病变Ⅲ级治疗与预后分析

目的探讨宫颈上皮内瘤样病变Ⅲ级(CINⅢ)的治疗方法。方法对1972年至1998年在我院治疗的宫颈原位癌48例和宫颈重度不典型增生28例进行回顾性分析。结果原位癌患者中,行次广泛全子宫切除术的29例和全子宫切除术的11例,术后均无复发;6例行宫颈锥形切除术,1例术后14年再次发生原位癌;重度不典型增生的患者,行子宫切除术和锥切术患者均无复发。结论宫颈CINⅢ发病年龄出现年轻化趋势,全子宫切除术与次广泛全子宫切除术预后相近,全子宫切除术可作为原位癌患者的首选治疗方法;单纯宫颈锥切术有术后复发可能,术后应严密随访;重度不典型增生可行宫颈锥切术或LEEP手术,术后应定期随诊。     

宫颈癌与宫颈上皮内瘤变组织中mPGES-1与COX-2的表达及意义

目的:探讨宫颈癌与宫颈上皮内瘤变(CIN)组织中mPGES-1和Cox-2的表达及意义。方法:采用实时荧光定量PCR法,分别检测我院手术切除宫颈癌组织和各级CIN组织中mPGES-1和COX-2的mRNA表达。结果:宫颈癌与CIN组织中mPGES-1和COX-2的表达量显著增高,分别是正常组织的110倍和25倍,两者的mRNA表达量和肿瘤的病理类型或分级相关,低分化的肿瘤组织表达量高。结论:mPGES-1mRNA在宫颈癌与宫颈上皮内瘤变组织中显著高于良性组织,并且和组织病理类型、分级有关,和COX-2表达呈直线正相关。这对宫颈癌及宫颈上皮内瘤变的诊断及治疗均有重要意义。     

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.     

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。     

Adherence to follow-up in women with cervical intraepithelial neoplasia grade 1

ObjectivesAdherence to follow-up is crucial for cervical intraepithelial neoplasia grade 1 (CIN1) because these women have a chance of progression to high-grade premalignant cervical lesions and cervical cancer. This study aimed to evaluate the rate of adherence to follow-up in women who were initially diagnosed with CIN 1 over a period of 24 months and to evaluate the regression and progression rate of CIN 1.Material and methodsOf 1050 women who visited a colposcopy clinic from October 2013 through March 2017, 138 with histologically proven as CIN 1 were recruited. Adherence to follow-up, the regression and progression rate of CIN 1 were retrospectively assessed.ResultsOf the 138 women, 86 (62.3%) followed regularly until the study endpoint at 24 months. During the study period, 10 women received ablative treatment. The regression rate in women who had surveillance with cervical cytology was 69.7%, persistent disease of 18.4%, and progression to CIN 2–3 of 11.8%. In contrast, 80% of women who received ablative treatment had regression, 20% of them had persistent disease but none had progression.ConclusionsNearly 40% of women with CIN 1 were lost to follow-up at 24 months. Adherence to the follow-up should be emphasized to all women. Intensive interventions to improve adherence and clinical outcome might be an option, particularly among women with poor compliance.     

Surgical management of cervical intraepithelial neoplasia in HIV-infected women

Objective

Rates higher than 50% of positive margin after surgical treatment of cervical intraepithelial neoplasia (CIN) have been reported in HIV-infected women. We evaluated the efficacy of two excisional procedures, loop excision of the transformation zone (LLETZ) and electrosurgical conisation, in obtaining complete excision of CIN in HIV-infected patients.

Study design

Eighty HIV-infected women with CIN or suspicion of cervical cancer underwent 86 surgical excisions. The indication of surgical modalities depended on both the size and location of the lesion and on the length of the cervix. Univariate logistic regression was used to identify factors associated with positive surgical margins.

Results

Preoperative colposcopy failed to visualize the entire transformation zone in 39% of cases, and showed that 93% of the lesions had endocervical extension. LLETZ was performed in 30 cases and electrosurgical conisation in 56 cases. Resection was complete, with negative margins, in 77% of cases (95% confidence interval, CI: 62–92%) after LLETZ and in 71% of case (95% CI: 60–83%) after electrosurgical resection. Residual disease was mostly located in the endocervical portion of histological specimen. During follow-up late complications such as cervical stenosis or unsatisfactory colposcopy were not observed.

Conclusion

Endocervical extension of CIN being frequent among HIV-infected women, LLETZ should not be the preferred procedure. Appropriate surgical management leading in reducing the rate of positive margins may help decreasing the risk of persistence or recurrence of lesions.     

子宫颈电环切除术对203例宫颈上皮内瘤变的疗效研究

目的 探讨宫颈电环切除术(LEEP)手术方法和有关术后并发症的关系及其预防措施，手术后标本的观察处理原则。方法 1995年5月至2002年4月采用LEEP对203例宫颈上皮内瘤变(CIN)患者进行治疗，对其疗效作回顾性分析。结果 术前术后病理诊断一致占40．39％(82／203)；术后病理诊断级别下降占53．20％(108／203)，其中下降一级占25．62％，下降两级占19．2l％，下降三级占8．37％；术后病理诊断级别上升占6．4|D％(13／203)，其中上升一级占5．42％，上升两级占0．98％。宫颈管受累占5．9l％(12／203)。合并单纯子宫内膜增生过长占23．15％(47／203)。手术切缘阳性5例，其中CINI3例，CINⅡ、Ⅲ各l例。术后3个月细胞学检查为不典型鳞状上皮细胞占12．32％(25／203)，其余均为正常。术中出血达10mL仅2例，94．09％(190／203)的患者术后第2-18天出现少量阴道血性分泌物。术后子宫颈管解剖狭窄7例，术后盆腔痛16例。术后半年无CIN占193例。治愈率为95．07％；宫颈CIN残留5例，占2．46％；第1年内复查发现CINⅡ持续1例。术后妊娠20例次，足月阴道分娩4例，剖宫产同时绝育l例，7例现继续妊：娠已达中晚期。早期妊娠人工流产4例，宫外孕2例。早孕延期流产2例，未发现早产及低出生体重儿。结论 LEEP是治疗CIN的安全有效方法，只要掌握手术指征。规范手术步骤，注意术后病理观察，可获得满意疗效。     

CYP1A1 gene polymorphism as a risk factor for cervical intraepithelial neoplasia and invasive cervical cancer

OBJECTIVE: The purpose of this study was to evaluate the role of CYP1A1*3 gene polymorphism in the development of cervical cancer by comparing patients having cervical intraepithelial neoplasia (CIN) or invasive cervical cancer with control subjects. METHODS: CYP1A1*3 polymorphism was analyzed using an allele-specific PCR-based method. RESULTS: In the group of patients with CIN, the frequency of the Ile/Val and of any Val alleles was significantly higher than in the healthy control subjects (OR: 4.51; 95%CI = 2.42-8.43, and OR: 3.71; 95%CI = 2.03-6.78). In the CIN1 group, patients with Ile/Val and any Val genotypes were found to be significantly higher (OR: 10.53; 95%CI = 3.78-29.33 and OR: 8.38; 95%CI = 3.04-23.08). In the CIN2 group, patients with Ile/Val and any Val revealed a 4.06- and 3.23-fold higher risk than those with Ile/Ile (95%CI = 1.54-10.74 and 1.24-8.45). However, the variance in the group of patients with CIN3 did not reach statistical significance. Patients with cervical cancer were analyzed with respect to the histological diagnoses. In the adenocancer group, the estimated ORs with respect to the control subjects were 11.29 for Ile/Val (95%CI = 3.35-38.07) and 8.98 for any Val groups (95%CI = 2.69-30.01), with a statistical significance. Among the squamous cell cancer patients, Ile/Val and any Val were significantly higher than in controls (OR: 5.76; 95%CI = 3.13-10.59 and OR: 5.20; 95%CI = 2.91-9.28). Although Val/Val genotype did not reach a significant value, it was near significance with an OR of 3.03 (95%CI = 0.95-9.68). CONCLUSION: These results suggest that CYP1A1*3 gene polymorphism is linked to a propensity for cervical carcinogenesis and further series are needed to detect the exact role of this unique variation.     

宫颈冷刀锥切治疗宫颈上皮内瘤样病变Ⅲ级的评价

目的 探讨阴道镜下多点活检与宫颈冷刀锥切对于宫颈上皮内瘤样病变Ⅲ级（CINⅢ）病理诊断的符合情况。方法 1995—2005年间对北京大学人民医院92例阴道镜下多点活检病理诊断为CINⅢ的患者进行宫颈冷刀锥切治疗，比较阴道镜下多点活检与宫颈冷刀锥切的病理结果之间的差异。结果 92例中有52例多点活检与冷刀锥切的病理结果一致，符合率为56．5％，40例多点活检与冷刀锥切的结果不同，其中11例多点活检诊断为CINⅡ／Ⅲ，而冷刀锥切诊断为微小浸润癌。结论 宫颈锥切是宫颈上皮内瘤样病变的一种重要诊断与治疗方法。阴道镜下多点活检病理提示宫颈上皮内瘤样病变Ⅲ级并伴随腺体受累可能是存在宫颈浸润癌的一个高危因素。人乳头瘤病毒（HPV）感染与宫颈病变有关，但未发现HPV高危型检测数值高低与患者病理级别之间的联系。     

Histology of cervical intraepithelial neoplasia and the role of biomarkers

Accurate histological grading of cervical intraepithelial neoplasia (CIN) lesions is important for clinical management of patients, because CIN1 and CIN2 and 3 lesions are treated differently. In general, there tends to be poor inter and intra-observer reproducibility of CIN grade evaluation among pathologists. In particular, the differential diagnosis between immature squamous metaplasia and CIN1 and 2, or between low-grade (CIN1) and high-grade (CIN2 and 3) lesions, tend to be difficult. These difficulties mean that patients tend to be over-treated for CIN lesions, which will naturally regress. Collectively, this highlights the need for alternative approaches and specific biomarkers to aid objective CIN lesion grading, and to identify true high-grade cervical disease. In this review we focus on the aetiology, pathobiology, the natural history of CIN, current issues with diagnosis and classification of CIN and the diagnostic and prognostic utility of specific biomarkers in identifying true cancerous precursor lesions.