高危型人乳头状瘤病毒第二代杂交捕获试验筛查宫颈癌及其癌前病变的验证研究

[目的]验证高危型人乳头状瘤病毒第二代杂交捕获试验(hybridcaptureⅡ,HC-Ⅱ)作为初筛方法检出宫颈病变(≥CINⅡ)的灵敏度和特异度,从而评价HC-Ⅱ检测的临床有效性。[方法]分别以自然人群(山西省襄垣县、沁县)和医院门诊(中日友好医院、北京大学第三医院)妇女为筛查对象的横断面研究,以病理诊断为金标准,开展HC-Ⅱ检测方法的临床验证。筛查对象接受检查时,依次留取Autocyteprep液基细胞学(LCT)和HC-Ⅱ检测标本,并对以上任一项异常者召回行阴道镜下检查和/或活检。[结果]1285例中高危型HPV感染339例,占26.4%;阴性946例,占73.6%。其中在1059例自然人群中高危型HPV感染163例,占15.4%;阴性896例,占84.6%;而在226例医院门诊病例中高危型HPV感染176例,占77.9%;阴性50例,占22.1%。最终参加HC-Ⅱ验证统计分析的共1273例,其中病理诊断≥CINⅡ的160例,HPV阳性同时病理诊断≥CINⅡ的157例。HC-Ⅱ检测样本的灵敏度和特异度分别为98.1%(157/160)和84.5%(941/1113)。阴性预测值和阳性预测值分别为99.7...     

宫颈癌集中筛查与机会性筛查中HPV检测的对比分析

目的探讨不同人群中HPV检测在宫颈癌防治中的地位。方法2004年1月~12月江西省妇幼保健院肿瘤科采用第2代杂交捕获试验(HC-Ⅱ)对3175例妇女进行13种高危型HPV脱氧核糖核酸(DNA)检测,其中1879例为江西修水县进行宫颈癌普查者和另1296例为该科门诊妇科疾病患者。结果宫颈癌普查与妇科门诊随机筛查中HPV的阳性率随宫颈病变程度的增加而增加(P<0.01),宫颈癌普查中HPV检测CINⅡ以上的灵敏度和特异度分别是0.974,0.548;妇科门诊筛查中HPV检测CINⅡ以上的灵敏度和特异度分别是0.907,0.567,宫颈癌普查和妇科门诊筛查中HPV检测CINⅡ以上的灵敏度和特异度均无显著性差异(P>0.01);阴性预计值分别是0.886和0.984,两者无显著差异(P>0.01)。结论HPV检测适用于宫颈癌的初筛查,但HPV的检测成本较高,尤其在经济欠发达地区,还不能完全用于大面积的宫颈癌集中筛查时,我们可选择性地在重点人群中(高风险人群)进行高危HPV的机会性筛查。     

宫颈癌的筛查及临床诊治

宫颈癌是女性的第二杀手，是HPV感染的疾病。有合理的筛查方案，两种HPV疫苗已经用于临床．辅助检查方法多，手术和化放疗效果肯定。文章主要就以上进行论述。     

HPV检测在农村宫颈癌筛查中的作用

[目的]了解HPV检测在辽宁省沈阳市苏家屯地区农村妇女宫颈癌筛查过程中的作用,为宫颈癌筛查提供科学依据.[方法]对2014～2015年间自愿接受宫颈癌筛查的35～64岁农村常住妇女,进行调查、取样和HPV检测.[结果]对10 000名35～64岁妇女进行宫颈癌筛查,发现宫颈癌癌前病变80人(其中CIN1为36人,CIN2为30人,CIN3为14人),宫颈癌3人.高危型HPV阳性共1209人,高危型HPV阳性感染率随年龄的升高而升高.HPV的感染率随着病变程度加重而升高;宫颈上皮内瘤变和宫颈癌组HPV 16型的比例显著性高于其他组.[结论] HPV检测在宫颈癌的筛查过程中对提高早诊率具有重要的意义.     

高危型HPV检测在宫颈癌筛查中的临床研究进展

宫颈癌的发生率仍高居女性生殖系统恶性肿瘤的首位。近年来的研究表明,宫颈癌和高危险型人乳头状瘤病毒（high—risk human papill—omavirus,HR-HPV）之间存在着明确的相互联系,HPV感染是宫颈癌的主要病因。同时许多可靠证据表明在宫颈上皮内瘤变（CIN）、尤其是CIN2、3的筛查中,HPV检测比宫颈细胞学检查具有更高的敏感性。     

江西省修水县宫颈癌筛查分析

目的:了解我国宫颈癌高发之一的江西省修水妇女宫颈癌的流行状况和高危型人乳头状瘤病毒(HPV)感染与宫颈癌的关系。方法:对江西修水县2460名妇女进行妇科检查,宫颈刮片细胞学检查,对可疑病例采集其宫颈细胞进行高危型HPVDNA检测(HCⅡ)或对其行阴道镜检查。结果:以病理诊断为金标准,普查的2460例已婚妇女中宫颈癌10例,CINⅡ6例,CINⅠ8例。该人群宫颈癌的患病率为40650/10万,高危型HPVDNA检出率为245%(70/286),HPVDNA检出率随病变程度加重呈趋势性增高,χ2=773,P<001。结论:江西省修水县是宫颈癌高发区,女性生殖道高危型HPV感染是当地宫颈癌及宫颈内瘤样病变(CIN)高发的重要危险因素。对宫颈癌高发区进行有效筛查十分必要。     

国产HPV杂交捕获技术在农村宫颈癌筛查中的应用

目的 人乳头瘤病毒(human papillomavirus,HPV)检测是国内外公认的宫颈癌筛查有效方式.近年来,我国研发了低成本、快速、简单的HPV检测方法,为HPV检测应用到人群筛查提供了希望.本研究分析国产HPV杂交捕获技术(hybrid capture 2,HC2)初筛不分流及DH2初筛HPV16/18分型检测分流检出宫颈癌前病变与宫颈癌的情况,评价此种检测技术应用于农村地区宫颈癌筛查的可行性.方法 按整群抽样的方法,对新密市7个乡镇35～64岁的农村妇女使用DH2检测进行宫颈癌筛查,阳性者召回做阴道镜,对镜下发现的可疑病变取活组织检查,病理诊断作为金标准,宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)≥2级(CIN2+)患者需手术治疗.对DH2阳性者同时进行HPV16/18分型检测,探索DH2初筛和HPV16/18分型检测分流策略对宫颈疾病的检出情况 .结果 DH2筛查阳性率为12.23％(1 512/12 358),其中≥50岁组HPV感染率和＜50岁组HPV感染率分别为13.40％(749/5 588)和11.27％(763/6 770),比值比(odds ratio,OR)=1.22(1.09～1.36),差异有统计学意义,x2=12.98,P＜0.001.共检出CIN2+ 87例(0.72％),CIN3+ 50例(0.41％),达到新密市近年最高水平.采用HPV16/18分型检测分流策略的阳性率为2.66％(319/11 981),检出CIN2+ 62例(0.52％),CIN3+ 37例(0.31％).HPV16/18分流检出CIN2+占总病例的73.81％(62/84),检出CIN3+占总病例的77.08％(37/48).结论 DH2检测对宫颈癌前病变及宫颈癌的检出率较高,可作为宫颈癌筛查方法使用.HPV16/18分流策略虽然可以降低阴道镜转诊率,但是会漏诊部分CIN2+患者,漏诊患者的基因型别有待进一步分析.     

宫颈癌的筛查及临床诊治

宫颈癌是女性的第二杀手，是HPV感染的疾病。有合理的筛查方案，两种HPV疫苗已经用于临床．辅助检查方法多，手术和化放疗效果肯定。文章主要就以上进行论述。     

p14ARF与宫颈癌及癌前病变的相关性研究进展

p14ARF是新近发现的一个抑癌基因，是细胞周期网络的重要成员。通过p53-MDM2和非p53通路监控细胞周期，从而抑制肿瘤的发生。p14ARF在大多数原发肿瘤中缺失，其失活机制以纯合子缺失、半合子缺失、杂合性缺失、启子5’CpG异常甲基化为主。但在宫颈癌及其癌前病变中不同的是，p14ARF在几乎所有宫颈癌及癌前病变中呈高表达，且表达随着宫颈癌病理分级的增高、临床分期的变晚而增强，究其原因可能与宫颈癌及其癌前病变中高危型HPV持续感染有关。文章就这方面的研究进展作一综述。     

Concordance in Cervical HPV Detection between Hybrid Capture 2 and HPV GenoArray Tests

HPV type-specific detection may promote cervical screening program and vaccination developmentworldwide. We conduct a study comparing HPV Hybrid capture II (HC II) Test and Hybribio GenoArray test,a newly developed HPV type-specific assay, in patients with cervical epithelial neoplasm. Results showed agood concordance in cervical HPV detection between two tests (kappa value 0.80, p<0.05, McNemar test). Ourstudy may promote utilization of type-specific HPV detection that is helpful for cervical cancer screening andvaccination.     

山西省襄垣县采用careHPV检测技术进行宫颈癌初筛的效果分析

[目的]评价careHPV检测技术在农村宫颈癌筛查中的应用情况.[方法]对山西襄垣县2270名35～64岁妇女采用careHPV检测技术进行官颈癌初筛,初筛阳性者接受液基细胞学分流,分流阳性者召回阴道镜检查及活检,以病理结果为金标准.[结果]参加筛查的妇女平均年龄45.7±6.8岁,careHPV阳性率为12.9％(292/2270),阴道镜转诊率为4.8％(109/2270),CIN1、CIN2+检出率分别为1.4％(31/2270)和1.7％(38/2270).在既往筛查史上,参加过筛查的妇女CIN2+的检出率要低于从未参加过筛查的妇女(x2=4.50,P=0.042).[结论]careHPV检测技术初筛细胞学分流的筛查策略有助于在降低阴道镜转诊率的同时,提高宫颈病变的检出率,扩大筛查覆盖面.该策略适用于资源相对贫乏的农村地区.     

人乳头瘤病毒基因分型检测在宫颈癌筛查中的应用进展

高危人乳头瘤病毒的持续感染是宫颈癌发生的直接因素.人乳头瘤病毒(human papillomavirus,HPV)检测从不分型到部分分型及拓展分型,不断发展并在宫颈癌筛查管理的更新完善中发挥重要作用,全球多个指南推荐HPV基因分型用于宫颈癌的初筛及初筛后分流管理.在HPV疫苗用于宫颈癌一级预防的后疫苗时代,全基因分型检...     

Mapping HPV Vaccination and Cervical Cancer Screening Practice in the Pacific Region-Strengthening National and Regional Cervical Cancer Prevention

Objective : To provide background information for strengthening cervical cancer prevention in the Pacificby mapping current human papillomavirus (HPV) vaccination and cervical cancer screening practices, as wellas intent and barriers to the introduction and maintenance of national HPV vaccination programmes in theregion. Materials and Methods: A cross-sectional questionnaire-based survey among ministry of health officialsfrom 21 Pacific Island countries and territories (n=21). Results: Cervical cancer prevention was rated as highlyimportant, but implementation of prevention programs were insufficient, with only two of 21 countries andterritories having achieved coverage of cervical cancer screening above 40%. Ten of 21 countries and territorieshad included HPV vaccination in their immunization schedule, but only two countries reported coverage of HPVvaccination above 60% among the targeted population. Key barriers to the introduction and continuation ofHPV vaccination were reported to be: (i) Lack of sustainable financing for HPV vaccine programs; (ii) Lackof visible government endorsement; (iii) Critical public perception of the value and safety of the HPV vaccine;and (iv) Lack of clear guidelines and policies for HPV vaccination. Conclusion: Current practices to preventcervical cancer in the Pacific Region do not match the high burden of disease from cervical cancer. A regionalapproach, including reducing vaccine prices by bulk purchase of vaccine, technical support for implementationof prevention programs, operational research and advocacy could strengthen political momentum for cervicalcancer prevention and avoid risking the lives of many women in the Pacific.     

Diagnostic Value of the CareTM HPV Test in Screening for Cervical Intraepithelial Neoplasia Grade 2 or Worse

Background: Cervical cancer is the fourth leading cause of cancer death in women worldwide. Persistent infection with a high risk human papillomavirus (HR-HPV) is the main etiological factor, so that early early detection of HR-HPV is very important. The aim of this study was to investigate the efficacy of CareTM HPV, a new method, as compared with Pap smear, PCR, and biopsy for screening purposes. Material and Method: In this cross-sectional study, 200 sexually active women aging from 25-50 years referred to the oncology clinic of Shahid Sodoughi Yazd Hospital in 2015 with a variety of cervix epithelial lesions or a need for colposcopy were enrolled. Results for CareTM HPV test (cervical), Pap smear, PCR, and biopsy were analyzed using SPSS 15 software and chi-square test, McNemar, and ROC curve analysis. Qualitative variables were compared using a Chi-square test. Results: CareTM HPV test sensitivity in detecting cervical intraepithelial neoplasia grade II (CIN-II) and also positive and negative predictive values were higher as compared to with other tests (p<0.05). The Pap smear test specificity was highest. There was no significant differences between CareTM HPV and PCR tests regarding detection of HPV-DNA in cases of CIN-II and worse (p>0.05). Conclusion: The CareTM HPV test has high sensitivity and predictive values for detecting HPV infection, with higher efficacy than the Pap smear test for tracking CIN-II. Therefore it may be recommended for use as a screening test in low-income areas.     

HPV58型在粤东地区宫颈癌中的病毒含量和感染状态研究

[目的]建立灵敏而稳定的人乳头状瘤病毒(human papillomavirus,HPV)58型病毒含量与整合状态检测方法,并探讨HPV58型在我国粤东地区妇女宫颈癌中的感染特征。[方法]PCR扩增HPV58E2和E6基因,PCR产物纯化,连接入T载体,构建标准品;检测30例宫颈癌和40例对照组织样本中HPV58的病毒含量和整合状态。[结果]成功构建含有HPV58E2或E6片段的T载体质粒作为检测HPV58型的病毒含量和判断感染状态标准品。HPV58型在宫颈癌中的感染率和病毒含量较正常宫颈组织均高,并且HPV58在粤东地区宫颈癌中的感染状态以整合型(66.67%)和混合型(33.33%)为主,和正常宫颈组织中感染状态分布有显著差异。[结论]采用荧光定量PCR法所建立的HPV58型病毒含量和整合状态的检测方法具有灵敏性和稳定性,HPV58型在粤东地区宫颈癌中的感染以整合状态为主。     

Prevalence and Genotype Distribution of HPV among Women Attending a Cervical Cancer Screening Mobile Unit in Lampang,Thailand

A growing body of literature is evidence that identifying subtypes of high-risk human papillomavirus (HR-HPV) has impacted on various steps of cervical cancer prevention.Thus, it is mandatory to determine the background prevalence and distribution of HPV subtypes for designing and implementing area-specificmanagement. The present study was conducted to evaluate prevalence and distribution of HPV subtypes among women aged 30-70 years living in Lampang, an area with a high incidence of cervical cancer, through use of a mobile screening unit. Of 2,000 women recruited in this study, 108 (5.40%, 95%CI: 4.45-6.48) were found to have HR-HPV infection. Risk was significantly correlated with age and number of partners. Singly or in combination, the most common genotype was HPV 52 (17.6%), followed by HPV 16 (14.81%), HPV 58 (13.89%), HPV 33 (11.11%), HPV 51 (11.11%), and HPV 56 (9.26%). HPV 18 was found in only 5.6% of cases. Together, HPV 16/18 were noted in approximately 20.4% of cases. Eighteen(16.67%) women were positive with multiple subtypes of HR-HPV. Co-infection most frequently involved HPV 16 or HPV 58. These findings have obvious implications for vaccine policy.     

HPV、HSV和CMV感染与宫颈癌的关系

背景与目的： 探讨宫颈癌前病变和宫颈癌的发生发展与人乳头状瘤病毒及单纯疱疹病毒(Herpes Simplex Virus,HSV)、巨细胞病毒(Cytomegalovirus,CMV)的关系。 材料与方法： 对81例不同宫颈病变组织进行HPV16/18和HPV6/11原位杂交,同时对103例不同宫颈病变组织用DNA扩增法检测HPV、HSV和CMV。 结果: 病毒DNA原位杂交信号的分布与HE染色中挖空细胞的分布一致。 HPV16/18与不同宫颈病变组织原位杂交阳性率平均为51.1 ％,HPV6/11的则为64.7 ％。经PCR检测,HPV16/18 、HPV6/11、HSV、CMV在不同宫颈病变组织中的阳性率分别为21 ％、4 ％、23 ％、0 ％。 结论： HPV感染具有特定的组织学部位,HSV可协同HPV16/18恶性转化宫颈上皮细胞。     

Hybrid capture-II and LCR-E7 PCR assays for HPV typing in cervical cytologic samples.

As part of an ongoing cohort study in the Hokuriku region of Japan, cervical cell samples from histologically confirmed normal (n = 114) or abnormal (n = 286) women were examined for the presence of HPV DNA using a second-generation hybrid capture assay (HCA-II) and LCR-E7 PCR. HCA-II detected low-risk (HPV-6, -11, -42, 43 and -44) and high-risk (HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59 and -68) HPV types, while LCR-E7 PCR detected an additional 7 HPV types and some uncharacterized types. In screening of high-grade squamous intraepithelial lesions (HSILs) and invasive cervical cancer, the sensitivities of HCA-II and LCR-E7 PCR testing the high-risk HPV types were 83% and 81%, respectively, while the specificity of both assays was 93%. The sensitivity of LCR-E7 PCR increased to 87%, which was significantly higher than that in HCA-II, when testing both high-risk and other HPV types. Sixty-eight inconsistent results (17% of total tested) from HCA-II and LCR-E7 PCR were due to (i) low copy number of HPV genome (false-negative for HCA-II, 5.3% and for LCR-E7 PCR, 1.3%), (ii) infection with HPV types undetectable by HCA-II (4.8%), (iii) multiple HPV infections (5%) or (iv) unknown reasons (0.8%). LCR-E7 PCR revealed that infections with HPV-16, -18, -31, -33, -35, -51, -52, -56, -58 or -67 was a high risk for cancer since these types predominated in HSIL and invasive cervical cancer. Samples showing high relative light units (>20) with a high-risk probe in HCA-II also gave positive results in LCR-E7 PCR and were generally associated with abnormal cervical lesions. Thus, we propose that both HCA-II and LCR-E7 PCR are valuable screening tests for premalignant and malignant cervical lesions.