宫颈上皮内瘤变及早期宫颈癌术中冰冻病理诊断及临床意义

目的探讨宫颈上皮内瘤变(CIN)及早期宫颈癌术中冰冻病理诊断价值、临床意义及如何提高术中冰冻诊断准确率.方法对70例CIN及早期宫颈癌患者术前阴道镜活检病理、术中冰冻病理、术后病理诊断结果进行回顾性对照分析.结果术中共有16例(16/70)病理级别上升,发现浸润癌6例;CINⅡ级～Ⅲ级、原位癌或镜下疑早浸3个等级的病理改变率分别为82.35%(28/34)、56.25%(18/32)、50.00%(2/4).结论术中冰冻病理诊断可以弥补术前活检取材表浅之不足,可以进一步判断宫颈病变程度,尤其是有无浸润及浸润深度等,为临床决定手术方式、范围提供较准确依据.     

阴道镜联合HPV检测对宫颈癌及宫颈上皮内瘤变的诊断价值

目的探讨阴道镜联合高危型人乳头瘤病毒(HR-HPV)检测对宫颈癌及宫颈上皮内瘤变的诊断价值。方法对644例行宫颈癌筛查的妇女行阴道镜和HR-HPV检测,并应用阴道镜取宫颈多点活组织进行病理检查。结果HR-HPV诊断结果阳性率为17.70%,阴道镜诊断结果阳性率为18.01%,HR-HPV+阴道镜诊断结果阳性率为18.79%;HR-HPV+阴道镜检测灵敏度和符合率与单一使用阴道镜或HR-HPV检测比较,P<0.05,差异具有统计学意义;HRHPV检测低危病变阳性率和高危病变阳性率比较,P<0.05,差异具有统计学意义。结论阴道镜联合HR-HPV检测可提高宫颈癌及宫颈上皮内瘤变的诊断灵敏度和符合率,高危病变HR-HPV检测阳性率更高。     

宫颈环切术诊治宫颈上皮内瘤变和早期宫颈癌

由于宫颈上皮内瘤变 (CIN)和宫颈癌的早期发现日渐增多 ,患者年龄日趋年轻化 ,宫颈环形电切术 (L EEP)应用于诊断和治疗也不断增加。 L EEP用于治疗宫颈鳞状上皮内瘤变的成功率可达91%～ 98% [1,2 ]。环形电刀是由电极尖端产生高频 (3 .8MHz)电波接触身体后 ,由组织本身阻抗、吸收电波而瞬间产生高热以达到切割效果。术者可通过圆、方、三角形等多种形状而调整所切组织的大小 ,是一种简便、安全的方法。本组研究通过对宫颈 CIN和早期宫颈癌术前 L EEP诊断的结果选择合适的手术方式 ,比较其病理变化 ,讨论 L EEP对宫颈病变的诊断及…     

Survivin在宫颈上皮内瘤样变及宫颈癌中表达的初步研究

目的：探讨Survivin基因表达与宫颈癌发生发展的关系。方法：应用免疫组化技术（SP法）,检测Survivin基因在10例正常宫颈组织、5例上皮内瘤样变及59例宫颈鳞癌中的表达。结果：Survivin在正常宫颈组织中不表达,在宫颈上皮癌变过程中表达阳性率逐级升高。Survivin表达阳性率与宫颈癌的组织学分级和临床分期呈正相关。结论：Survivin基因表达发生在宫颈癌恶性转化的早期,并为宫颈癌预后提供了有价值的判断指标。     

P16INK4A在宫颈上皮内瘤变中的表达及与HPV感染的关系

目的 探讨抑癌基因P16INK4A在宫颈上皮内瘤变中的表达情况及其与HPV感染的相关性.方法 采用免疫组化染色法,对59例宫颈上皮瘤变(CIN)标本、30例病理检查为正常宫颈组织的标本进行检测.结果 CIN Ⅰ级组织中ILK表达阳性率62.50％、CIN Ⅱ～Ⅲ级为65.71％,均显著高于正常宫颈组织(23.33％),且差异均具有统计学意义(x2=8.472,P=0.004＜0.05;x2=11.675,P=0.001 ＜0.05);CIN Ⅰ级组织中ILK表达阳性率与CIN Ⅱ～Ⅲ级比较差异无统计学意义(x2=0.064,P =0.800 ＞0.05).P16INK4A在HPV16、HPV18 2种高危型宫颈HPV感染中的表达显著高于其他高危型或者低危型(HPV53、HPV58、HPV6).结论 P16INK4A在宫颈上皮内瘤变(CIN)中显著高表达,同时P16INK4A高表达可能与HPV16、HPV18的阳性表达具有协同作用.     

高危型HPV亚型及亚型组合检测宫颈癌及高级别宫颈上皮内瘤变的比较研究

背景与目的：高危型人乳头状瘤病毒(high risk human papillomavirus,hrHPV)感染对于浸润性宫颈癌(invasive cervical carcinoma,ICC)及其癌前病变的致病性存在亚型及地区差异。本研究通过分析本地区30岁及以上女性宫颈病变患者中HPV亚型分布特点,进一步识别罹患包含ICC的高级别宫颈上皮内瘤变(cervical intraepithelial neoplasia grade 2 or worse,CIN2+)风险更高的亚型,并比较这些高风险亚型及亚型组合检测CIN2+病变的有效性。方法：收集来自复旦大学附属肿瘤医院就诊患者具备组织学随访结果的宫颈标本,行PCR-反向点杂交法(PCR-reverse dot blot,PCR-RDB)HPV基因分型检测,利用Logistic回归模型分析hrHPV亚型与CIN2+病变的风险关系,并构建ROC曲线(receiver operating characteristiccurve,ROC curve)评价不同亚型及亚型组合检测CIN2+病变的准确性。结果：符合研究要求患者413例,含38例CIN1,184例CIN2/3,126例ICC和65例阴性对照人群。HPV16、58、33和18依次为致CIN2+最常见的4种HPV亚型,仅HPV16(P<0.000 1)、58(P=0.002)及33(P=0.015)为罹患CIN2+病变的高风险亚型。联合检测HPV16/18/33/58诊断CIN2+病变的ROC曲线下面积(the area under the ROC curve,AUC)显著高于HPV16/18亚型组合(P=0.006 6)。结论：HPV16/18/33/58亚型组合用于辅助本地区CIN2+病变的检测可能更为有效。     

CK8在宫颈上皮内瘤变和宫颈癌中的表达及意义

目的探讨CK8在宫颈上皮内瘤变及宫颈癌中的表达及其临床意义。方法应用免疫组织化学S-P法检测15例正常宫颈组织、15例CINⅠ、17例CINⅡ、21例CINⅢ和36例宫颈癌组织中CK8的表达情况。结果 CK8在正常宫颈组织中无表达,在CIN和宫颈癌中的阳性表达率分别47.2%和80.6%,三组组间相比,差异有统计学意义(χ2=28.503,P<0.05)。CIN间,CINⅡ、CINⅢ组阳性率均高于CINⅠ组,差异有统计学意义(P=0.016;P=0.002)。随着宫颈病变程度的加重,CK8的阳性表达率逐渐增高,其阳性表达率同宫颈病变程度呈正相关关系(γ=0.979,P<0.01)。结论 CK8在宫颈组织恶性转化过程中,随着病变程度的加重,阳性表达率逐渐增高。CK8可作为高级别CIN和宫颈癌诊断及预测病变进展趋势的标志物。     

HPV负荷量与宫颈上皮内瘤变关系的研究

[目的]探讨持续感染高危型人乳头瘤病毒（HPV）的病毒负荷量与宫颈上皮内瘤变（CIN）的关系。[方法]采用杂交捕获二代（HC-Ⅱ）方法定量检测CIN患者HPV—DNA的含量,全部269个病例阴道镜下多点取活组织病理检查,分析病毒负荷量与宫颈病变严重程度的相关性。[结果]HPV总阳性率为46．84％（126／269）。高危型HPV在慢性宫颈炎、CIN Ⅰ、CINⅡ及CINⅢ的阳性半分别为13．5％、48．2％、73．8％及93．7％;慢性宫颈炎、CINⅠ、CINⅡ以及CINⅢ的HPV—DNA含量分别为147．9±9．7、328．5±24．6、354．1±29．8以及374．2±34．8,CIN的HPV—DNA含量明显高于慢性宫颈炎（P〈0．05）,但不同级别CIN之间比较,差异无显著性（P〉0．05）。[结论]HPV—DNA含量检测可作为宫颈上皮内瘤变的筛查及病情追踪监测的一项客观指标。     

Impact of an HPV6/11/16/18 L1 virus-like particle vaccine on progression to cervical intraepithelial neoplasia in seropositive women with HPV16/18 infection

The impact of a human papillomavirus (HPV) vaccine on development of cervical intraepithelial neoplasia grade 2-3 or adenocarcinoma in situ (CIN2-3/AIS) in women with ongoing HPV16 or 18 infections prevaccination is reported. Seventeen thousand six-hundred and twenty-two women aged 16-26 were enrolled in 1 of 2 randomized, placebo-controlled, efficacy trials (Protocols 013 and 015). Vaccine or placebo was given at day 1, month 2 and 6. Women were tested for HPV6/11/16/18 DNA and antibodies at day 1. We focus on the subset of women who were seropositive and DNA positive to HPV16 or HPV18 prevaccination. Incidence is expressed as the number of women with an endpoint per 100 person-years-at-risk. In total, 419 vaccine and 446 placebo recipients were both seropositive and DNA positive to HPV16 or HPV18 prevaccination and had at least one follow-up visit. In Protocol 013, the incidence of HPV16/18-related CIN2-3/AIS among these women was 10.9 in the vaccine arm and 7.0 in the placebo arm (vaccine efficacy = -54.9; 95% CI: -181.7, 13.0). In Protocol 015, the incidence of HPV16/18-related CIN2-3/AIS was 5.5 in the vaccine arm and 6.2 in the placebo arm (vaccine efficacy = 12.2%; 95% CI: -29.8, 40.9). These data suggest HPV vaccination neither reduces nor enhances progression to HPV16/18-related high grade cervical lesions, and cervical cytology screening and corresponding management should continue as per local recommendations. Ultimately, population-based surveillance of vaccinated individuals beyond these clinical trials will be required to further address questions regarding the impact of vaccination in women exposed to vaccine HPV types before vaccination.     

Chromosomal profiles of high-grade cervical intraepithelial neoplasia relate to duration of preceding high-risk human papillomavirus infection

High-grade cervical intraepithelial neoplasia (CIN2/3) represents a heterogeneous disease both with respect to clinical behavior and chromosomal aberrations detected. We hypothesized that the extent of chromosomal aberrations reflects the duration of their existence. Chromosomal profiles were determined of CIN3 of women with a known 5-year history of high-risk human papillomavirus virus (hrHPV) infection, in which duration of prior hrHPV infection was considered a proxy for duration of CIN3 existence. Eleven women had a <5 year preceding hrHPV infection (CIN3<5yrPHI) and 24 had a PHI lasting ≥5 years (CIN3≥5yrPHI). For comparison, six CIN3 adjacent to squamous cell carcinomas (CIN3-SCC), the corresponding SCCs, and six CIN1 were included. Unsupervised hierarchical clustering analysis of the chromosomal profiles revealed two clusters. One was characterized by a low number of chromosomal aberrations and included all CIN1, 81.8% of CIN3<5yrPHI and 33.3% of CIN3≥5yrPHI. Samples in the second cluster, displaying multiple aberrations, included 18.2% of CIN3<5yrPHI, 66.7% CIN3≥5yrPHI, all except one CIN3-SCC and all SCCs. The number of genomic aberrations increased according to lesion grade and also with longer duration of PHI. The increase in aberrations in CIN3≥5yrPHI compared to <5yrPHI was highly significant (p = 0.001), suggesting that CIN3≥5yrPHI represent more severe lesions. In conclusion, longer duration of preceding hrHPV infection is associated with an increased number of chromosomal aberrations. Hence, CIN3 with a longer duration of existence are likely more prone to have an increased short-term risk of cervical cancer.     

光动力治疗人乳头瘤病毒感染和宫颈上皮内瘤变的临床应用进展

光动力疗法是联合应用光敏剂及其相关光源,利用光动力学反应选择性破坏肿瘤组织的治疗方法.目前光动力疗法作为一种新的疗法已经在HPV感染和CIN的治疗中广泛应用并取得了良好的治疗效果,通过对国内外光动力疗法在治疗HPV感染及CIN的临床应用的综述,可以为进一步深入研究提供理论依据.     

Differences in human papillomavirus type distribution in high‐grade cervical intraepithelial neoplasia and invasive cervical cancer in Europe

Knowledge of differences in human papillomavirus (HPV)‐type prevalence between high‐grade cervical intraepithelial neoplasia (HG‐CIN) and invasive cervical cancer (ICC) is crucial for understanding the natural history of HPV‐infected cervical lesions and the potential impact of HPV vaccination on cervical cancer prevention. More than 6,000 women diagnosed with HG‐CIN or ICC from 17 European countries were enrolled in two parallel cross‐sectional studies (108288/108290). Centralised histopathology review and standardised HPV‐DNA typing were applied to formalin‐fixed paraffin‐embedded cervical specimens dated 2001–2008. The pooled prevalence of individual HPV types was estimated using meta‐analytic methods. A total of 3,103 women were diagnosed with HG‐CIN and a total of 3,162 with ICC (median ages: 34 and 49 years, respectively), of which 98.5 and 91.8% were HPV‐positive, respectively. The most common HPV types in women with HG‐CIN were HPV16/33/31 (59.9/10.5/9.0%) and in ICC were HPV16/18/45 (63.3/15.2/5.3%). In squamous cell carcinomas, HPV16/18/33 were most frequent (66.2/10.8/5.3%), and in adenocarcinomas, HPV16/18/45 (54.2/40.4/8.3%). The prevalence of HPV16/18/45 was 1.1/3.5/2.5 times higher in ICC than in HG‐CIN. The difference in age at diagnosis between CIN3 and squamous cervical cancer for HPV18 (9 years) was significantly less compared to HPV31/33/‘other’ (23/20/17 years), and for HPV45 (1 year) than HPV16/31/33/‘other’ (15/23/20/17 years). In Europe, HPV16 predominates in both HG‐CIN and ICC, whereas HPV18/45 are associated with a low median age of ICC. HPV18/45 are more frequent in ICC than HG‐CIN and associated with a high median age of HG‐CIN, with a narrow age interval between HG‐CIN and ICC detection. These findings support the need for primary prevention of HPV16/18/45‐related cervical lesions.     

Persistence of HPV infection and risk of high-grade cervical intraepithelial neoplasia in a cohort of Colombian women

Little is known about the dynamics of human papillomavirus (HPV) infection and subsequent development of high-grade cervical intraepithelial neoplasia (CIN2/3), particularly in women >30 years of age. This information is needed to assess the impact of HPV vaccines and consider new screening strategies. A cohort of 1728 women 15–85 years old with normal cytology at baseline was followed every 6 months for an average of 9 years. Women with squamous intraepithelial lesions were referred for biopsy and treatment. The Kaplan–Meier method was used to estimate the median duration of infection and Cox regression analysis was undertaken to assess determinants of clearance and risk of CIN2/3 associated with HPV persistence. No difference in the likelihood of clearance was observed by HPV type or woman''s age, with the exception of lower clearance for HPV16 infection in women under 30 years of age. Viral load was inversely associated with clearance. In conclusion, viral load is the main determinant of persistence, and persistence of HPV16 infections carry a higher risk of CIN2/3.     

Human papillomavirus genotype in cervical intraepithelial neoplasia grades 2 and 3 of Taiwanese women

We aimed to assess the distribution of human papillomavirus (HPV) genotypes in high‐grade cervical lesions in Taiwan. The study included 1,086 paraffin‐embedded, formaldehyde‐fixed cervical intraepithelial neoplasia (CIN) 2/3 specimens. HPV genotyping was performed using polymerase chain reaction (PCR)‐based methods. Multiple HPV types were validated by E6 type‐specific PCR, direct sequencing and/or real‐time PCR. HPV DNA was detected in 995 (91.6%) specimens, and multiple HPV types were identified in 192 (19.3%) samples. The leading HPV types were HPV16 (24%), HPV52 (20%), HPV58 (20%), HPV33 (13%), HPV31 (8%) and HPV18 (4.6%). Although the leading six types consisted of 87.6%, HPV16 or 18 comprised only 30.9%. The prevalence of different HPV types showed a significant association with age. In women older than 50 yr, HPV16 and 18 comprised 21.3% (83/389), while HPV52, 58 and 33 represented 55.5% (216/389). In women aged less than 50 yr, HPV16 and 18 comprised 32.1% (224/697, p < 0.0001), while HPV 52, 58 and 33 represented 47.9% (334/697, p = 0.02). The distribution of HPV genotypes was compared with previously reported findings for Taiwanese women with cervical cancer (CC). The overall HPV16 positivity rate was significantly higher in CC than in CIN 2/3 (odds ratio: 2.14, 95% CI: 1.91–2.40). In addition, HPV18, 39 and 45 were significantly overrepresented in CC, whereas HPV52, 58, 33, 31, 35, 51 and 53 were underrepresented. We concluded that an effective vaccine against the most common HPV types could prevent a significant proportion of cervical cancer cases that occur in Taiwan.     

宫颈癌和宫颈上皮内瘤变中表皮生长因子受体表达与人乳头瘤病毒16和(或)18感染及其相互关系

目的探讨宫颈癌发生发展过程中,表皮生长因子受体(EGFR)与人乳头瘤病毒(HPV)的作用及其相互关系。方法宫颈癌组60例,选自1997年至2001年间中山大学肿瘤防治中心住院初治的宫颈癌病例,临床分期Ⅰa～Ⅱb期;宫颈上皮内瘤变(CIN)组40例;正常上皮对照组30例。以免疫组化S-P法检测宫颈组织EGFR的表达,以PCR检测HPV16和(或)HPV18感染。结果正常上皮组、CIN组和宫颈癌组的EGFR中强表达率呈梯度上升,分别为0、42.5%和76.7%,差异有统计学意义(P<0.05)。正常上皮组、CIN组和宫颈癌组的HPV16和(或)HPV18感染率分别为6.7%、67.5%和58.3%,宫颈癌组和CIN组的感染率均显著高于正常上皮组(P=0.000),但宫颈癌组与CIN组之间,差异无统计学意义(P=0.355)。肿瘤侵袭程度超过宫颈1/2间质者,EGFR中强表达率显著高于未达1/2间质者(89.2%:56.5%,P=0.004)。宫颈管侵袭者HPV16和(或)HPV18感染率显著高于无侵袭者(88.2%:46.5%,P=0.003)。EGFR与HPV之间无显著相关性(P>0.05)。EGFR与HPV均未显示与宫颈癌预后有关。结论EGFR和HPV与宫颈癌的发生发展有关;EGFR、HPV16和(或)HPV18与宫颈癌预后无关,EGFR与HPV16和(或)HPV18无显著相关性。     

HPV E6/E7 mRNA和HPV DNA检测技术在宫颈上皮内瘤变中的诊断价值分析

目的比较人乳头瘤病毒(HPV)E6/E7 mRNA和HPV DNA检测技术对宫颈上皮内瘤变(CIN)2级及以上(CIN2+)患者的诊断价值,并评价HPV E6/E7 mRNA检测结果在不同实验室间的一致性。方法采用HPV E6/E7 mRNA和HPV DNA检测技术对212例门诊体检的健康者和住院的宫颈病变患者的宫颈脱落细胞学标本进行检测。以病理诊断结果为金标准,评价两种检测技术诊断CIN2+的灵敏度和特异度。北京市迪安中心实验室和北京市怀柔妇幼保健院实验室均采用HPV E6/E7 m RNA检测技术检测同一批标本,评价实验室间检测的一致性。结果HPV E6/E7 m RNA检测的阳性率为38.7%,与HPV DNA的阳性率43.9%比较,差异无统计学意义(P﹥0.05)。HPV E6/E7 mRNA和HPV DNA的检测阳性率均随着病理分级的升高而增加(P<0.01)。HPV E6/E7mRNA检测CIN2+的灵敏度为92.96%,与HPV DNA的90.14%相比,差异无统计学意义(P﹥0.05),而HPV E6/E7mRNA检测CIN2+的特异度为88.65%,高于HPV DNA的79.43%,差异有统计学意义(P<0.05)。两个实验室采用HPV E6/E7 m RNA检测阳性一致的标本例数为78,阴性一致的标本例数为121,总一致率为93.87%,Kappa=0.872,一致性较好。结论与HPV DNA检测技术相比,HPV E6/E7 mRNA检测宫颈病变的特异度更具优势,实验室间重复性检测的一致率较高,有望成为中国宫颈癌HPV筛查的首选方法。