宫颈特殊染色法、液基薄层细胞学及人乳头瘤病毒检测对宫颈癌前病变的应用价值分析

目的:探讨宫颈特殊染色法(FRD)、液基薄层细胞学(TCT)及人乳头瘤病毒(HPV)检测对宫颈癌前病变筛查的应用价值。方法:选取2015年1月～2018年1月于我院行宫颈癌筛查的1794例妇女作为研究对象,所有研究对象均接受FRD、TCT、HPV检测,以经阴道镜取样活检结果为阳性标准,对比分析三种不同检测方法以及联合检测的诊断效能。结果:病理科活检检出阳性111例,检出率为6.19%;FDR检测检出阳性114例,检出率为6.35%,漏诊率为16.22%;TCT检测检出阳性115例,检出率为6.41%,漏诊率为19.82%;HPV检测检出阳性108例,检出率为6.02%,漏诊率为19.82%;FRD检测与TCT、HPV检测的检出率比较差异无统计学意义(P0.05)。FRD检测敏感度为83.78%,特异度为98.75%,阳性预测值为81.58%,阴性预测值为98.93%;TCT检测敏感度为80.18%,特异度为98.46%,阳性预测值为77.39%,阴性预测值为98.69%;HPV检测敏感度为80.18%,特异度为98.87%,阳性预测值为82.41%,阴性预测值为98.70%;FRD、TCT、HPV联合检测敏感度为93.69%,特异度为99.52%,阳性预测值为92.86%,阴性预测值为99.58%;FRD、TCT、HPV联合检测与FRD、TCT、HPV单独检测的敏感度、阳性预测值比较差异具有统计学意义(P0.05)。结论:FRD、TCT、HPV检测对宫颈癌前病变的诊断效能相当,而FRD、TCT、HPV联合检测的诊断效能优于各方法单独检测。     

TCT、HPV检测在宫颈锥切术后复发中的预测价值

目的:评估薄层液基细胞学检查(thinprep cytologic test,TCT)和人乳头瘤病毒(human papillomavirus,HPV)检测在宫颈锥切术后复发中的预测价值。方法:随访531例病理诊断为子宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)Ⅱ-Ⅲ级接受宫颈锥切术的患者,分别于术后3、6个月及术后每6-12月随访1次,以TCT及HPV检测作为随访的检测指标,若二者有一项异常,行阴道镜下活组织检查,病理证实存在子颈上皮内瘤变Ⅰ-Ⅲ级者视为复发。采用敏感度、特异度、阳性预测值、阴性预测值表示TCT、HPV检测性能。结果:531例患者中10%(54例)的患者出现不同级别的病变复发。TCT在术后预测病变复发的灵敏度77%,特异度72%;HPV在术后预测病变复发的灵敏度95%,特异度60%,TCT联合HPV预测病变复发的灵敏度100%,特异性80%。术后HPV负荷量100 RLU/PC者较HPV负荷量100 RLU/PC者而言术后病变复发的风险增高,差别有统计学意义(P0.01),术后HPV负荷量100 RLU/PC是锥切术后病变复发的高危因素。结论:使用细胞学联合HPV检测是有效的预测宫颈锥切术后病变复发的方法,术后高HPV负荷量与病变复发相关,并可对术后复发高风险人群进行分流,临床需严密随访。     

液基细胞、HPV检测与阴道镜宫颈癌的筛查方面的应用研究

目的:探讨液基薄层细胞学检查、HPV-DNA检测、阴道镜检查在宫颈癌早期诊断中的临床应用价值.方法:回顾性分析92例宫颈液基薄层细胞学检查未能明确诊断意义的宫颈非典型鳞状细胞病变患者,进行HPV-DNA检测与阴道镜检查,将检测的结果进行对比研究.结果:阴道镜与宫颈液基薄层细胞检查(TCT)及HPV检测在宫颈上皮内瘤变的灵敏度相比,差异有统计学意义(P＜0.05),阴道镜的检出率最高.随着TCT结果的病变级别提高,HPV感染率也提高,ASCUS组与LSIL组之间差异有统计学意义(P＜0.05).ASCUS、LSIL、HSIL病理活检的阳性率差异明显(P＜0.05),有统计学意义.宫颈的不同病变年龄主要集中在31-50岁之间.结论:宫颈液基薄层细胞学检查异常的患者,应进行HPV检测及阴道镜下活检,三步筛查法可大幅度提高宫颈高度病变的检出率,并且30-50岁的女性应定期做宫颈细胞学检查、HPV检测及阴道镜检查.     

TCT联合HPV检测诊断宫颈病变的临床价值分析

目的:探讨新柏氏液基细胞学技术(TCT)联合人乳头瘤病毒(human papilloma virus,HPV)检测诊断宫颈病变的临床价值。方法:选择哈尔滨医科大学附属第一医院妇科门诊收治的6752例患者,采集其宫颈脱落细胞进行TCT检测,登记患者的年龄及宫颈外观。分别随机选取TCT阳性和阴性结果的患者144例进行HPV检测及阴道镜下活检,分析和比较TCT单独及联合HPV检测诊断宫颈病变的敏感性和特异性。结果:宫颈柱状上皮细胞的外移程度及患者的年龄与宫颈TCT结果均无显著相关性。单独TCT检测诊断宫颈病变的灵敏度为87.04%,特异性为58.55%;单独HPV检测诊断宫颈病变的灵敏度为62.96%,特异性为81.62%;而联合测诊断宫颈病变的灵敏度为100%,特异度为48.29%。结论:TCT联合HPV检测可显著降低宫颈病变的漏诊率。     

细胞学结合高危型HPV-DNA检测在宫颈病变筛查中的应用

目的:评价现行3种子宫颈癌及癌前病变筛查方法的诊断效果.方法:对我院2009年1月～12月105位24～71岁妇女,均实施宫颈刮片细胞学和液基细胞学检查(TCT)、杂交捕获2代实验(HC2)检测高危型人乳头瘤病毒(HR-HPVDNA)、阴道镜取宫颈组织做病理检查,以病理检查结果为标准,≥中度官颈上皮内瘤变(CIN2)为阳性,检测各筛查方法的灵敏度及特异度.结果:各筛查方法的灵敏度及特异度分别为:宫颈刮片细胞学检查(≥巴氏Ⅲ级为阳性)(0.829,0.615)、TCT(≥ASCUS/AGUS为阳性)(0.845,0.594)、HR.HPV DNA(≥1.00为阳性)(0.902,0.400)、宫颈刮片细胞学与HR-HPV DNA联合检测(二项均阳性)(0.780,0.677)、TCT与HR-HPVDNA联合检测(二项均阳性)(0.805,0.692).宫颈刮片细胞学检查、TCT、宫颈刮片细胞学检查联合HR-HPV DNA、TCT联合HR-HPV DNA受试者工作特征(receiver operating characteristic,ROC)曲线下面积、可信区间(confidence interval)分别为0.719(0.620-0.819),0.724(0.625-0.822),0.729(0.629-0.828),0.749(0.652.0.849),各筛查方法筛查效率间差异无统计学意义.结论:宫颈刮片细胞学检查、液基细胞学检查(TCT)以及HR-HPVDNA检测是目前宫颈癌筛查有价值的方法,宫颈刮片细胞学检查与TCT检查相比筛查效率相似,分别联合HR-HPVDNA检测后筛查效率无明显增加.     

恒温扩增HPV检测技术应用于子宫颈癌筛查的效果评价研究

为了评价人乳头状瘤病毒(Human papillomavirus,HPV)恒温DNA扩增检测技术用于高危型HPV检测和宫颈癌早期及癌前病变筛查的准确性和可行性。本研究于2016年6月至8月,在我国内蒙古地区招募2 774例30-64岁有性生活史的妇女进行宫颈癌筛查;采用薄层液基细胞学技术完成细胞学诊断。采用恒温DNA扩增HPV检测技术(Isomega)和第二代杂交捕获技术(Hybrid Capture 2,HC2)平行检测宫颈标本;对于Isomega检测为HPV16/HPV18阳性的标本和两种方法检测不一致的标本,使用线性探针法(INNO-LiPA)进行分型验证。以病理诊断为金标准,评价Isomega用于筛查宫颈上皮内瘤变(Cervical Intraepithelial Neoplasia,CIN)2级及以上患者的灵敏度和特异度。结果表明,Isomega与HC2检测高危型HPV的总一致率为92.72%(Kappa=0.74),阳性一致率为86.78%,阴性一致率为93.77%;以INNO-LiPA分型结果为标准,Isomega检出HPV16和HPV18的准确率分别为96.97%和86.11%。以病理诊断为金标准,Isomega筛查CIN2+的灵敏度和特异度分别为87.76%和82.94%。Isomega能准确检测HPV16、HPV18和其他高危型别HPV,有较高的筛查灵敏度和特异度。     

高危型HPV筛查与TCT 联合检查在宫颈癌筛查中的临床应用

目的:探究液基薄层细胞学检测(TCT)与高危人乳头瘤病毒(HR-HPV)筛查联合检查在宫颈癌(CC)筛查中的临床价值。方法:选择2013年4月~2015年4月期间我院就诊疑似CC患者318例为研究对象;研究对象均进行HR-HPV筛查、TCT检查及阴道镜下病理活检,评价三种筛查结果的临床应用价值。结果:318例可疑CC患者中,病理学诊断炎症患者162例(50.94%),宫颈上皮内瘤样变(CIN)患者151例(47.48%),鳞癌(SCC)患者5例(1.57%);HR-HPV、TCT及HPV+TCT联合对诊断结果与病理诊断的符合率分别为78.30%、85.22%和99.37%;HR-HPV与TCT单独检测的符合率随患者病情进展呈现升高趋势(P0.05);TCT、HR-HPV检测单独进行诊断的敏感度、特异度均低于联合诊断(P0.05);HR-HPV与TCT联合检测诊断CC的敏感度为98.71%、特异度100%。结论:TCT检查HR-HPV筛查联合检查CC的敏感性、特异性及准确性高,为CC筛查的有效方式,值得在临床应用推广。     

人乳头瘤病毒感染与宫颈高级别病变关系的研究

目的探讨人乳头状瘤病毒(human papillomavirus,HPV)感染与宫颈高级别病变(highgrade squamous intraepithelial lesion,HSIL)的关系。方法选取2003年1月到2016年8月在首都医科大学附属北京天坛医院行宫腔镜辅助宫颈冷刀锥切术的患者181例,患者行宫腔镜辅助宫颈冷刀锥切术前均有HPV检测、薄层液基细胞学(TCT)以及阴道镜活检及免疫组化的结果。依据病检结果分析HPV感染与宫颈高级别病变的关系。结果在181例宫颈高级别病变中,HPV感染165例,HPV检测阳性率为91.16%。其中高危型HPV感染160例,阳性率为88.40%,占阳性标本的96.97%。HPV16阳性率57.46%,占高危型HPV感染的63.03%。40~49岁高危型HPV检测阳性率最高,但各年龄组比较差异均无统计学意义(各年龄组P值均0.05)。HPV感染在宫颈高级别病变和子宫颈癌中差异均有统计学意义(P0.05)。结论 HPV感染在宫颈高级别病变的发生和发展中起关键作用。高危型HPV基因分型诊断在宫颈癌筛查及防治过程中具有重要意义。     

FRD特殊染色技术在宫颈疾病筛查中的结果分析

目的:研究FRD特殊染色技术(FRD)在宫颈疾病筛查中的结果情况,为临床诊疗提供依据。方法:选取2015年5月到2016年5月我院就诊宫颈疾病筛查者306例,对所有患者进行FRD和液基细胞学检测,两种检测有一项提示阳性则行阴道镜病理检测,以病理检测为标准,比较两种检测方法诊断价值。结果:宫颈癌前病变和宫颈癌筛查中两种检测方法敏感度分别为87.6%、84.0%,特异性分别为69.0%、63.3%,诊断符合率分别为79.7%、75.8%,阳性预测值分别为79.2%和78.4%,阴性预测值分别为81.7%和71.4%,Kappa值为0.56和0.48,比较差异无统计学意义(P0.05)。结论:FRD与液基细胞学检测筛查宫颈癌前病变和宫颈癌效果相似,但是FRD操作简便,值得在临床上应用。     

HPV病毒感染与宫颈炎症及宫颈癌之间的关系及意义分析

目的研究人乳头瘤病毒(HPV)在宫颈炎症、宫颈癌前病变及宫颈癌中的水平及临床意义。方法分别选取宫颈炎症278例、宫颈癌前病变174例、宫颈腺癌82例、宫颈鳞癌183例患者,并以218例宫颈无病变的病例作为对照,所有患者均行薄层液基细胞学(TCT)检查及阴道镜下病理活检,检测各组患者间HPV阳性水平并对统计结果加以分析。结果 218例宫颈无病变病例中高危性HPV阳性率为9.6%(21/218),其余717例宫颈出现病变的患者中高危型HPV筛查结果阳性例数为405例,阳性检出率56.5%,且随着宫颈病变严重程度的加重,高危型HPV检出率逐渐升高(P0.01),但是宫颈腺癌和宫颈鳞癌组的高危型HPV阳性率比较差异无统计学意义(P0.05)。结论 HPV是宫颈癌前病变及宫颈癌的主要致病因素,对宫颈炎症、宫颈癌前病变及宫颈癌患者行HPV检测对于患者早日确诊及早日治疗具有重要意义。     

薄层液基细胞学检测及HPV检测对宫颈癌筛查价值的系统评价

目的：系统评价薄层液基细胞学检查（TCT）及人类乳头状病毒（HPV）检查在子宫颈癌筛查中的应用价值。方法：检索收集2000年以来,Cochrane数据库、Pubmed、MEDLINE、Webofscience、EMBASE、万方数据库、清华同方数据库、维普数据库中与TCT及HPv检测在宫颈癌筛查（癌前病变及早期宫颈癌）诊断方面的相关文献,参照Cochrane系统评价的方法对资料进行统计分析。结果：共有12篇文献纳入研究,TCT合并的敏感性0．65（95％CI,0．62-0．68）,特异性0．93（95％CI,0．92-4）．93）,阳性预测值8．25（95％CI,5．65-12．04）,阴性预测值0．27（95％CI,0．18-0．41）,合并SROC曲线下面积AUC=0．889,Q值0．819。HPV合并敏感性0．69（95％CI,O．67~0．71）,特异性O．91（95％CI,0．90-0．91）,阳性预测值3．93（95％CI,2．99-5．18）,阴性预测值0．17（95％CI,0．09～0_31）,合并SROC曲线下面积AUC=0．871,Q值0．801。结论：薄层液基细胞学检查在宫颈癌筛查中具有较高的诊断准确度,与HPV联合检测可提高诊断的准确性。     

人乳头状瘤病毒DNA检测在宫颈病变筛查中的应用研究

目的：探讨高危型人乳头状瘤病毒（HR-HPV）DNA检测方法在宫颈病变筛查中的应用意义。方法：580例妇女同时进行薄层液基细胞学（TCT）、第2代杂交捕获法（HC Ⅱ）和阴道镜下宫颈组织活检,并以病理组织学检查结果作为确诊标准进行对比分析。结果：①580例受检者中病理诊断为炎症207例（35.69%）,CIN Ⅰ 224例（38.62%）,CIN Ⅱ 96例（16.55%）,CIN Ⅲ 38例（6.55%）,浸润癌15例（2.58%）;②TCT检测异常者中炎症52例（25.12%）,CIN Ⅰ 177例（79.02%）,CIN Ⅱ 85例（88.54%）,CIN Ⅲ36例（94.74%）,浸润癌15例（100%）,其中CIN Ⅱ和CIN Ⅲ组间差异无统计学意义（P〉0.05）,但显著高于炎症组和CIN Ⅰ组,低于湿润癌组（P〈0.01或0.05）;③HPV DNA检测阳性者中炎症66例（31.88%）,CIN Ⅰ 152例（67.86%）,CIN Ⅱ 83例（86.46%）,CINIII 35例（92.11%）,浸润癌组15例（100%）,除CIN Ⅱ和CIN Ⅲ组间差异无显著性外（P〉0.05）,其余各组间差异均有统计学意义（P〈0.05或0.01）,且HPV-DNA检测阳性组CIN和浸润癌发病率明显高于阴性组（P〈0.01）;④30岁以下高危险型HPV感染率（65.53%）显著高于30岁以上34.47%感染率（P〈0.01）;⑤联合应用TCT、HPV-DNA检测诊断宫颈癌及癌前病变的敏感度和特异度分别为96.14%和69.28%,高于TCT或HPV-DNA的单独检测。结论：宫颈高危险型HPV感染是CIN及宫颈癌的主要发病因素,并与病变严重程度密切相关,而HPV-DNA和TCT联合应用可提高宫颈癌及癌前病变的检出率。     

Evaluation of a cervical cancer screening program based on HPV testing and LLETZ excision in a low resource setting

We conducted studies in Vanuatu to evaluate potential screening and treatment strategies to assist with control of cervical cancer. In a pilot study of 496 women, visual inspection and cytology were evaluated as screening tests for detection of CIN 2 or worse (CIN2+), observed in 21 of 206 subjects biopsied on the basis of abnormal visual inspection or cytology. Sensitivity of visual inspection with Lugol's Iodine for detection of CIN2+ on biopsy was 0.63, specificity was 0.32, and the positive predictive value was 0.09. For HSIL cytology, sensitivity was 0.99, specificity was 0.77, and the positive predictive value was 0.88. HSIL cytology was significantly more sensitive and had a significantly higher PPV for CIN 2+ than visual inspection (p<0.01). In a further study of 514 women, we compared testing for HR HPV and cytology as predictors of biopsy proven CIN 2+. Sensitivity of HSIL cytology for CIN2+ as established by loop excision of the cervix was 0.81, specificity was 0.94, and positive predictive value was 0.48. Sensitivity of a positive test for HR HPV for detection of CIN2+ was non-significantly different from cytology at 0.81, specificity was 0.94, and positive predictive value was 0.42. Combining the two tests gave a significantly lower sensitivity of 0.63, a specificity of 0.98, and a positive predictive value of 0.68. For women over 30 in a low resource setting without access to cytology, a single locally conducted test for high risk HPV with effective intervention could reduce cervical cancer risk as effectively as intervention based on cytology conducted in an accredited laboratory.     

The ideal strategy for cervical cancer screening in Japan: Result from the Fukui Cervical Cancer Screening Study

Introduction

The aims of the Fukui Cervical Cancer Screening (FCCS) study are to determine the frequency of women with high‐risk HPV (hrHPV), whether HPV16 or HPV18 (HPV16/18), in the Japanese cancer screening population for the first time and to identify the best strategy for cervical cancer screening in Japan.

Methods

This study enrolled 7584 women aged ≥25 years who were undergoing routine screening. All women underwent LBC and cobas HPV tests. Women with abnormal cytology, whether hrHPV positive or negative; women with hrHPV positivity with either normal or abnormal cytology; and women randomly selected from women with normal cytology and negative hrHPV negative were referred for colposcopy.

Results

The prevalences of hrHPV positivity and HPV16/18 positivity were 6.8% and 1.7%, respectively. The baseline data from the FCCS study showed that the combination of HPV tests and cytology was more sensitive than cytology with respect to the detection of intraepithelial neoplasia grade 2 or worse. However, the specificity (94.1%) of the co‐testing strategy that required all women with abnormal cytology or hrHPV positivity to be referred for colposcopy was much lower than that (97.8%) of cytology. The sensitivity and specificity of the co‐testing strategy that required only women with abnormal cytology or HPV16/18 positivity to undergo colposcopy were 85.5% and 97.0%, respectively.

Conclusion

The baseline data from the FCCS study suggest that a cervical cancer screening strategy in which only women with abnormal cytology or HPV16/18 positivity undergo colposcopy offers a more balanced sensitivity and specificity than other strategies.     

Human papillomavirus DNA and liquid-based cervical cytology cotesting in screening and follow-up patient groups

OBJECTIVE: To compare the use of human papillomavirus (HPV) DNA and cervical cytology cotesting in screening and follow-up of patients with previous cervical abnormalities and to assess the significance of a positive HPV DNA test result in re-screening of cytologically normal cases. STUDY DESIGN: Cellular samples collected in liquid-based fixative were used for both cervical cytology and HPV DNA testing. The cervical cytology slides were manually screened by cytotechnologists followed by rapid re-screening by pathologists. The HPV DNA tests were performed using hybrid capture test kits. Statistical analyses of cervical cytology results and HPV DNA tests for high- and low-risk HPV from both patient groups were carried out. RESULTS: The prevalence of HPV DNA-positive cases was higher in younger patients. There was a poor correlation between cervical cytology results and HPV DNA tests for the screening group (kappa = 0.23), but a fair to good correlation was obtained for the follow-up group (kappa = 0.51). The false negative fraction of cytology negative/HPV DNA positive cases (0.1317), as compared with cytology negative/HPV DNA negative cases (0.0056), was statistically significant (p = 0.000001). CONCLUSION: The prevalence of HPV DNA decreased with increasing age in both the screening and follow-up patient groups. Virus clearance was delayed in the follow-up group as compared with the screening group. There was a poor correlation between cervical cytology and HPV DNA tests in the screening group but a fair to good correlation in the follow-up patient group. Cotesting of HPV DNA and cervical cytology increases the sensitivity and decreases the false negative fraction, suggesting that cotesting could be used to increase the interval of screening.