人乳头瘤病毒与宫颈上皮内瘤样病变术后复发的关系

宫颈上皮内瘤样病变（CIN）是一种癌前病变,可分为CINⅠ、CINⅡ和CINⅢ。国内对CINⅡ及以上者主要采取手术治疗,但术后仍有一定的复发率。影响复发的因素较多,包括切缘阳性、宫颈管诊刮阳性、机体免疫力降低、高龄等。人乳头瘤病毒（HPV）与CIN复发的关系尚不十分明确,但基本能够确定HPV持续感染可增加CIN复发率,且HPV亚型和HPV负荷量在其中起重要作用。综述HPV对CIN复发的影响。     

人乳头瘤病毒亚型检测在宫颈病变分流管理中的意义

宫颈癌在女性肿瘤中位居第二，占癌症患者总数的15％。每年约有371200个新发病例，约200000例死亡。由于经济水平低下以及缺乏宫颈肿瘤普查手段等因素，80％的新发病例发生在发展中国家。现已明确人乳头瘤病毒（HPV）感染是宫颈癌的根本致病因素。研究证实，大多数宫颈上皮内瘤样病变（CIN）伴有HPV感染，90％宫颈癌标本可以检测出HPVDNA。     

人乳头瘤病毒L1壳蛋白在子宫颈上皮内瘤变患者中的表达及其意义

目的检测人乳头瘤病毒（HPV）L1壳蛋白在宫颈上皮内瘤变（CIN）患者宫颈脱落细胞中的表达,以寻求预测CIN的生物学标志物。方法收集2008年12月至2011年8月在河南省漯河市中心医院有指征行阴道镜活检患者的宫颈脱落细胞标本480例,采用免疫细胞化学法检测HPVL1壳蛋白的表达。结果480例患者HPVL1壳蛋白的总阳性率为40．2％（193／480）,其中正常／慢性宫颈炎、CIN1、CIN2、CIN3和宫颈鳞状细胞癌（SCC）HPVL1壳蛋白的阳性表达率分别为40．5％（17／42）、66．2％（131／198）、26．4％（28／106）、17．3％（17／98）和0（0／36）。其中CIN1组、SCC组与正常／慢性宫颈炎组,CIN1组与CIN2／3组,CIN1、CIN2／3组与SCC组HPVLI壳蛋白阳性表达率比较,差异均有统计学意义（P均＜0．01）。结论HPVL1壳蛋白在宫颈上皮内瘤变中的阳性表达随病变程度的加重而呈下降趋势,提示其有望成为预测宫颈癌前病变程度的标志物。     

宫颈重度鳞状上皮内病变和宫颈癌组织中人乳头瘤病毒感染及基因分型的研究

目的:探讨人乳头瘤病毒感染及其基因型与宫颈重度鳞状上皮内病变(HSIL)和宫颈癌的关系.方法:采用可检测25种HPV基因型的基因芯片方法分别检测HSIL(23例)和宫颈癌(46例)组织的HPV基因型,计算两组患者宫颈组织中HPV的感染率及各基因型的感染率,比较HPV及其主要基因型与宫颈病变的关系.结果:69例宫颈病变患者中HPV阳性率为98.55%(68/69);HSIL组单一型别感染率为81.82%,多型别感染率为18.18%,HPV的型别分布以HPV16、52、58最常见;宫颈癌患者中单一型别感染率为95.45%,多型别感染率为4.55%,HPV的型别分布以HPV16、58最常见.所检出的HPV型别中以HPV16的检出率最高.结论:①HPV感染,特别是高危型HPV感染与HSIL和宫颈癌的关系密切;②宫颈病变严重程度可能与HPV基因型多寡无关,而与感染HPV亚型的致病能力密切相关;③HSIL与宫颈癌感染的HPV基因型呈多样性.且均为高危型感染,其中以HPV 16型最常见.     

人乳头瘤病毒及其相关宫颈上皮内瘤变的药物治疗进展

宫颈上皮内瘤变是由高危型人乳头瘤病毒(HPV)的持续性感染引起。高级别宫颈上皮内瘤变患者的治疗以手术切除病变组织为主。手术的治疗效果确切,但也可能带来一些术后并发症,如早产、低体重儿等。因此,药物治疗人乳头瘤病毒及其相关宫颈上皮内瘤变具有潜在的重要临床价值。本文就目前人乳头瘤病毒及其相关宫颈上皮内瘤变的药物治疗进展做一综述。     

高危型人乳头瘤病毒载量与宫颈上皮内瘤变病变程度相关性

目的:探讨高危型人乳头瘤病毒(HR-HPV)载量与宫颈上皮内瘤变(cervi-cal intraepithelial neoplasia,CIN)病变程度相关性。方法:对2008年1月~2010年6月于上海市第一人民医院行阴道镜检查的1035例患者,用HCⅡ方法检测其HR-HPV病毒载量,分为阴性组(0.00~1.00)、低度载量组(1.0~10.00)、中度载量组(10.00~100.00)、高度载量组(100.00~1000.00)和极高度载量组(≥1000.00);将病理结果按照宫颈病变程度分为阴性组(慢性黏膜炎和挖空细胞)、低级别病变组(CINⅠ)和高级别病变组(CINⅡ、CINⅢ)。多分类Logistic回归分析HPV病毒载量和CIN病变程度相关性。结果:病理诊断为慢性黏膜炎、挖空细胞、CINⅠ、Ⅱ、Ⅲ的HR-HPV病毒载量的中位数(感染率)分别是2.70(58.22%)、56.00(79.07%)、88.05(79.66%)、323.90(93.27%)和364.07(92.47%),基本呈递增趋势。CIN的各级别病毒载量的分布差异显著(P均<0.05),低级别病变组和高级别病变组的各级别病毒载量组(低度载量组、中度载量组、高度载量组和极高度载量组)对于病理阴性组的危险度(OR值)依次递增:低级别病变组0.677、2.406、2.893和2.943;高级别病变组2.177、4.262、6.354和20.177。结论:CIN的发生与高危型人乳头瘤病毒载量有关,病毒载量越高,CIN发生危险度越高。     

宫颈高度鳞状上皮内病变治疗后高危型人乳头瘤病毒的消退规律

目的探讨宫颈高度鳞状上皮内病变治疗后高危型人乳头瘤病毒(HPV)的消退规律,了解术后高危型HPV持续感染与病变残留或复发之间的关系。方法对2003年1月至2007年12月在广东省人民医院因宫颈高度鳞状上皮内病变行宫颈电环切除术的502例妇女的随访资料进行回顾性分析。结果术前存在高危型HPV感染的宫颈高度鳞状上皮内病变进行宫颈电环切除术治疗后,术后6、12、18、24个月HPV清除率分别为83.63%、94.39%、97.31%、98.88%。术后高危型HPV持续感染人群病变残留或复发率达26.85%。结论宫颈电环切除术后6个月高危型HPV己大部分消退,术后2年基本完全消退。术后宫危型HPV持续感染是病变残留或复发的高危因素,术后HPV阳性妇女,宜严密随访。     

人乳头瘤病毒16疫苗预防宫颈上皮内瘤样病变的效果

常见人乳头瘤病毒（HPV）型（包括HPV16）的预防性疫苗的出现给有效预防宫颈癌带来了希望。HPV病毒样颗粒（virus-like particle，VLP）疫苗预防持续性HPV感染的功效已被证实，但其预防作用是否能超过18个月以及对宫颈上皮内瘤样病变（CIN）Ⅱ～Ⅲ的影响尚不明确。     

HPV L1检测预测宫颈鳞状上皮内病变预后的意义

近年研究表明,随着宫颈鳞状上皮内病变(SIL)的进展,病变组织HPVL1衣壳蛋白表达呈下降趋势。联合宫颈HPVL1衣壳蛋白检测及现有筛查手段如细胞学、p16等检测也许可以提高其预测SIL预后的准确性。现将HPVL1检测用于预测SIL预后的科学性及实用性作一综述,以探索更加合理的筛查流程,对SIL患者进行最佳的分流管理。     

高危型HPV感染绝经后女性宫颈高级别鳞状上皮内病变的诊治

高级别鳞状上皮内病变（high-grade squamous intraepithelial lesion,HSIL）与高危型人乳头瘤病毒（human papilloma virus,HPV）持续感染有关,被视为宫颈癌前病变,有癌变潜能。绝经后女性由于宫颈的年龄依赖性变化,宫颈HSIL的诊治难度增加。虽然宫颈活组织检查是诊断宫颈病变的金标准,但也存在漏诊现象,然而宫颈管搔刮术可提高绝经期女性HSIL的诊断准确率,尤其阴道镜检查不满意但可疑宫颈病变时宫颈管搔刮术的效果更为显著。尽管切缘阳性被认为是宫颈切除后病变残留/复发的关键因素,切缘阴性也并不意味着病灶已被完全切除。而且因为宫颈萎缩、宫颈缩短和阴道穹窿部消失等原因使宫颈切除性手术操作困难,增加膀胱、直肠等邻近脏器损伤的风险,同时,绝经期女性激素水平降低,宫颈癌好发部位转化区内移至宫颈管内,阴道镜检查无法及时找到可疑部位,导致宫颈癌漏诊。因此,探讨针对绝经后女性宫颈病变的最优诊疗方案有重要的临床意义。通过分析绝经后女性宫颈HSIL的诊治现状及面临的难题,为绝经后妇女宫颈病变的个体化诊治提供理论指导。     

子宫颈液基细胞学检查异常的涂片中人乳头状瘤病毒L1蛋白的表达及其意义

目的 探讨人乳头状瘤病毒(HPV)L1蛋白在官颈液基细胞学检查异常涂片中的表达及其意义.方法 选择2006年9月-2008年9月间,在中日友好医院就诊的官颈液基细胞学检查诊断为≥未明确诊断意义的不典型鳞状上皮细胞(ASCUS),且其第2代杂交捕获试验(HC-Ⅱ)榆测HPV DNA结果均为阳性,同时有组织病理学诊断的患者共274例.其中,宫颈液基细胞学检查诊断为ASCUS 105例、低度鳞状上皮内病变(LSIL)119例、不除外高度病变的不典型鳞状上皮细胞(ASC-H)9例、高度鳞状上皮内病变(HSIL)36例、官颈鳞癌5例;组织病理学检查(作为金标准)诊断为炎症96例、宫颈上皮内瘤变(CIN)Ⅰ 85例、CIN Ⅱ 55例、CIN Ⅲ 32例、官颈鳞癌6例.对此274例患者的官颈涂片,采用伞反应抗体的免疫细胞化学染色进行HPV L1蛋白的榆测,分析其对官颈病变进展的预测价值.结果 274例患者中,组织病理学检杏诊断为炎症的组织中HPV L1蛋白阳性表达率为69.8%(67/96),CIN Ⅰ为83.5%(71/85),CIN Ⅱ为41.8%(23/55),CIN Ⅲ为3.1%(1/32),宫颈鳞癌为0(0/6),除CIN Ⅲ与官颈鳞癌比较,差异无统计学意义(P>0.05)外,其他不同病变问比较,差异均有统计学意义(P<0.01);细胞学检查诊断为LSIL的细胞中HPV L1蛋白阳件表达率(75.6%,90/119)最高,其次为ASCUS细胞(63.8%,67/105)和HSIL+宫颈鳞癌细胞(9.8%,4/41),3者问比较,差异有统计学意义(P<0.01).71例未经治疗的ASCUS、LSIL患者中,55例HPV L1蛋白阳性表达者中无一例疾病进展,16例HPV L1蛋白阴性表达者疾病进展的发生率为19%(3/16),两者比较,差异有统计学意义(P<0.01).结论 HPV L1蛋白在宫颈液基细胞学检查异常涂片中的表达情况可以帮助了解宫颈的病变程度,预测宫颈病变的发展趋势,尤其对细胞学检查诊断为ASCUS和LSIL的患者可协助指导临床处理.     

Risk factors for human papillomavirus persistence among women undergoing cold-knife conization for treatment of high-grade cervical intraepithelial neoplasia

Objective

To investigate the risk factors potentially associated with high-risk human papillomavirus (HPV) persistence in women undergoing cold-knife conization (CKC) for treatment of high-grade cervical intraepithelial neoplasia (CIN).

Methods

Medical records of women who underwent CKC for treatment of CIN 2/3 between 2007 and 2012 at a tertiary hospital in Ankara, Turkey, were retrospectively analyzed. Cases involving persistent HPV infection after 1 year of follow-up were identified. Using univariate and multivariate analyses, the impact of various factors such as patient age, menopausal status, parity, high-risk HPV type, excised cone dimensions (width, height, and depth), and surgical margin status on high-risk HPV persistence was assessed.

Results

A total of 292 women underwent CKC for treatment of CIN 2/3 within the study period. After women with a subsequent diagnosis of cervical cancer, subsequent total hysterectomy, and inadequate follow-up data were eliminated, 113 women were eligible for final analysis. High-risk HPV persistence was detected in 24 (21.2%) women, and multivariate analysis revealed that patient age and cone depth were significant independent predictors (P < 0.05).

Conclusion

High-risk HPV persistence may be encountered after CKC procedures. It is important to evaluate persistent HPV infections after treatment because affected women are at increased risk for disease persistence, recurrence, and progression.     

Apoptosis-related proteins and cervical intraepithelial neoplasia in human immunodeficiency virus-seropositive women

OBJECTIVE: To evaluate the expression of bcl-2, p-53, Ki-67, and apoptosis as evidenced by nuclear DNA fragmentation in cervical biopsies obtained from human immunodeficiency virus (HIV)-seropositive and HIV-seronegative women with a history of intravenous drug abuse. METHODS: We investigated 109 consecutive cervical biopsies (73 from HIV seropositive and 36 from HIV seronegative patients), including 86 cervical intraepithelial neoplasia (CIN) lesions and 23 normal cervical epithelium. The markers of apoptosis and proliferation were detected using immunostaining methods on paraffin sections. The associations between HIV status and the intensities of immunostaining were tested by univariate and multivariable methods. RESULTS: The severity of CIN correlated directly with the intensities of p-53 (Spearman Rho = 0.19; P = 0.05) and Ki-67 immunostaining (Spearman Rho = 0.46, P < 0.001) and with apoptosis and Bcl-2 expression (chi-square for trend = 10.6 and 3.91 , P < 0.001 and P = 0.048, respectively).After adjustment, by logistic regression analysis, for the potential confounding effect of severity of CIN and Human Papillomavirus (HPV) infection, apoptosis was five times more common in cervical biopsies of HIV seropositive compared to HIV seronegative patients (27 out of 73 as compared to 4 out of 36, adjusted Odds Ratio = 5.0; 95% confidence intervals = 1.56-16.33, P = 0.007). The adjusted odds ratio of increasing p53 immunodetection was significantly higher in biopsies obtained from HIV-seropositive patients compared to HIV seronegative controls (OR = 8.7; 95% confidence intervals = 2.97-25.3, P < 0.0001). CONCLUSION: Markers of apoptosis such as nuclear DNA fragmentation and p-53 immunoreactivity are more intensely expressed in cervical biopsies of normal and dysplastic epithelium of HIV-seropositive compared to HIV-seronegative women.     

宫颈上皮内瘤变与人类白细胞抗原及人乳头瘤病毒感染相关性的研究

目的:探讨宫颈上皮内瘤变(CIN)与人乳头瘤病毒(HPV)感染及人类白细胞抗原(HLA)的相关性。方法:选取宫颈活检组织病理学诊断为CINⅠ42例、CINⅡ40例、CINⅢ29例、宫颈湿疣40例、慢性宫颈炎90例,从液基薄片检测剩余的保存液中提取宫颈脱落细胞学的基因组DNA,采用PCR方法及HLA试剂盒进行HPV16/18及HLA分型检测。结果:HPV16/18检出率CINⅠ组为21.4%,CINⅡ组为47.5%,CINⅢ组为55.2%,湿疣组为32.5%,宫颈炎组为1.1%。HLA分型表明,DR15(2)、DQ6(1)、DQ4在CIN组中阳性率分别为37.0%、44.0%、12.0%,明显高于宫颈炎组的17.5%、18.8%、3.8%(P<0.05),并且DR4阳性率随着CIN级别增高而增高(CINⅠ5.6%,CINⅡ13.9%、CINⅢ28.6%)。结论:HPV16/18感染和HLA分型与CIN及其分级密切相关,提示HLA在宫颈癌的发生、发展中可能起一定的作用。     

miR-218下调与宫颈上皮内瘤变患者HPV病毒感染关系的研究

目的:探讨小分子RNA-218(miR-218)下调与宫颈上皮内瘤变(CIN)患者人乳头瘤病毒(HPV)感染的关系。方法:选择78例宫颈上皮内瘤变(CIN)患者,其中CINⅠ22例(28.2%),CINⅡ27例(34.6%),CINⅢ29例(37.2%),逆转录聚合酶链反应(RT-PCR)检测miR-218的表达,GenoArray测试工具包检测组织标本中HPV的表达。结果:miR-218在高危型HPV感染患者中的含量低于低危型HPV感染者,CINⅡ、Ⅲ患者miR-218含量比CINⅠ患者低。结论:高危型HPV感染患者中miR-218表达降低,提示miR-218可能是宫颈癌发生的重要因素。     

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.     

宫颈癌及上皮内瘤变人乳头瘤病毒基因型的检测

目的:了解宫颈癌及上皮内瘤变人乳头瘤病毒(HPV)的感染率及其基因型的分布。方法:用PCR-RFLP法检测239例宫颈癌及上皮内瘤变患者HPV感染并进行分型。先用PGMY09/11共同引物扩增生殖道粘膜型HPV L1区的高度保守区,然后联合使用RsaⅠ、MseⅠ、PstⅠ和HaeⅢ4个限制性内切酶对阳性PCR产物进行酶切,利用不同的酶切片段鉴定HPV的基因型。结果:在239例宫颈癌及上皮内瘤变患者中共检出205例(85·8%)HPV感染,其中宫颈上皮内瘤变Ⅰ级(CINⅠ)、宫颈上皮内瘤变Ⅱ~Ⅲ级(CINⅡ~Ⅲ)和宫颈癌中HPV感染率分别是66·7%,89·9%和98·3%,差异有统计学意义(P<0·001)。在宫颈癌及上皮内瘤变中共检出22型HPV,其中主要基因型及其感染率分别是HPV16(45·6%)、58(12·1%)和52(6·3%)。结论:宫颈癌及上皮内瘤变中HPV感染的基因型至少可达22型,其中以HPV16、58和52为最常见。     

Cost-effectiveness of human papillomavirus testing after treatment for cervical intraepithelial neoplasia

OBJECTIVE: To compare current cytological follow up of women treated for high-grade cervical intraepithelial neoplasia (CIN) with follow up by high-risk human papillomavirus (HPV) testing together with cytology. DESIGN: A cost-effectiveness modelling study. SETTING: Gynaecology clinics in the Netherlands. POPULATION: Women treated for high-grade CIN. METHODS: A Markov model was developed to compare six follow-up strategies with HPV testing with current cytological follow up at 6, 12, and 24 months. Model parameter estimation was based on three Dutch follow-up studies and a Dutch population-based screening cohort. MAIN OUTCOME MEASURES: The number of CIN2/3 cases missed after 5 years follow up, the number of diagnostic procedures, and costs involved. RESULTS: Strategies with adjunct HPV testing were more effective than current follow up (reduction in missed CIN2/3 cases 32-77%, corresponding to a number needed to treat of 192-455) and less inconvenient (reduction in repeat smears 28-65%). A particularly attractive strategy was HPV testing alone at 6 months and both HPV and cytological testing at 24 months after treatment. This strategy yielded a high detection rate of post-treatment CIN, did not lead to an increase in colposcopy rate, and was 49 Euro per woman cheaper than the current strategy. CONCLUSIONS: Our model supports the use of high-risk HPV testing for monitoring women treated for high-grade CIN.