hrHPV E6/E7 mRNA检测用于宫颈癌联合筛查的横断面研究

目的:研究hrHPV E6/E7 mRNA在宫颈癌联合筛查中的准确性,探索其用于宫颈癌联合筛查的临床价值。方法:选取2013年1月至2015年12月在青岛市市立医院和青岛市城阳区人民医院妇科门诊行宫颈癌机会性筛查的女性共6223例。根据宫颈筛查方法分组:宫颈液基薄层细胞学检查(LBC)+HC2组(LBC+HC2组);LBC+HPV分型组;LBC+hrHPV E6/E7 mRNA(LBC+E6E7组)。比较3种HPV+细胞学联检策略和细胞学单独筛查的灵敏度、特异度、阳性预测值、阴性预测值、阴道镜转诊率、CIN2+/CIN3+检出率及曲线下面积(AUC)。结果:LBC+E6E7联检CIN2+的灵敏度、特异度、PPV、NPV、阴道镜转诊率、CIN2+/CIN3+检出率分别为91.28%、95.50%、56.07%、99.43%、9.64%和5.40%;CIN3+分别为93.10%、92.06%、19.29%、99.85%、9.64%和1.86%。3种联合筛查策略之间比较,上述指标均无统计学差异(P0.05)。LBC+E6E7联检CIN2+/CIN3+的AUC分别为0.969和0.973,大于LBC单筛,差异有统计学意义(P0.05)。结论:hrHPV E6/E7 mRNA与细胞学联合筛查的准确性与HC2、HPV分型+LBC联检无明显差异,可作为HPV-DNA的替代用于宫颈癌机会性筛查的联检方案。     

Aptima HPV E6/E7mRNA技术检出宫颈癌及癌前病变的临床效果研究

目的评估Aptima HPV E6/E7 mRNA检测技术在宫颈癌筛查人群和临床就诊患者中检出宫颈癌及癌前病变的效果。方法选取我国山西省长治市3个三甲医院参加宫颈癌筛查的21~70岁妇女及门诊病人共557人作为研究对象,采用LBC与HPV E6/E7 mRNA检测技术对宫颈细胞学标本进行检测,以病理学结果作为诊断金标准,评价两种方法检测宫颈癌及癌前病变的临床效果。结果 HPV E6/E7 mRNA阳性率随着细胞学和病理病变级别的升高而升高。在CIN2+/CIN3+中,HPV E6/E7 mRNA检测的灵敏度与特异度均高于LBC检测;HPV E6/E7mRNA检测的ROC曲线下面积均大于LBC检测。结论 HPV E6/E7 mRNA检测出宫颈癌及癌前病变的能力相比于LBC检测更具优越性。     

高危型人乳头瘤病毒E6/E7 mRNA与其DNA检测在子宫颈病变中的对比研究

目的探讨高危型人乳头瘤病毒(HR-HPV)E6/E7 m RNA及HPV DNA检测与宫颈病变的关系。方法选取2013年1月至2015年12月在青岛市市立医院妇科门诊行宫颈癌联合筛查的两组女性:LCT+HRHPV DNA(HC2组,n=2 417);LCT+HR-HPV E6/E7 m RNA(E6/E7组,n=2 906)。细胞学ASCUS+或HPV阳性转诊阴道镜行宫颈活检。计算HPV m RNA E6/E7与HPV DNA在不同病理结果中的阳性率、病毒载量及在CIN2+中的一致率。结果 (1)在病理正常、CIN1、CIN2、CIN3和ICC中E6/E7 m RNA阳性率分别为61.36%、76.00%、92.11%、96.00%和100.00%,随病变程度加重而升高(P0.05)。正常病理结果中E6/E7组HPV的阳性率低于HC2组(χ2=7.764,P=0.005)。(2)E6/E7组病毒载量的中位数和四分位数在不同病理结果中分别为629.72(339.31,2 122.94),1117.33(319.17,3 101.88),1 537.12(422.19,4 219.05),3 396.59(1 217.32,6 316.81),10 860.43(3 473.19,29 662.29),随着病变程度加重逐渐升高,差异有统计学意义(P0.05)。(3)在CIN2+患者中,E6/E7组和HC2组的一致率为82.64%,Kappa值=0.69。结论 HPV E6/E7阳性率与HC2一样随着宫颈病变程度的加重逐渐升高。HPVE6/E7 m RNA与HPV DNA诊断CIN2+的一致性较好。HPV E6/E7载量可能反映病变程度,但还需进一步临床验证。     

HPV E6/E7 mRNA检测在LBC-/HPV+女性临床管理中的应用价值

目的:探讨HPV E6/E7 mRNA检测在LBC-/HPV+女性临床管理中的应用价值。方法:收集2017年12月至2019年9月在临沂市人民医院自愿接受液基细胞学(LBC)联合HR-HPV DNA(包含HPV16/18分型)或HPV E6/E7 mRNA检测进行宫颈癌筛查,结果为LBC-/HPV+且后续转诊阴道镜及组织病理学检查患者628例,以病理诊断结果为金标准,分析比较两种HPV检测方法对LBC-/HPV+患者人群发生高级别及以上宫颈病变(≥HSIL)的风险预测能力。结果:628例LBC-/HPV+患者中,共检出≥HSIL患者80例(12.74%),其中以30～39岁组检出率最高(17.89%)。490例HR-HPV DNA阳性患者≥HSIL总检出率为10.00%(49/490),双+组检出率最高(14.89%,14/94);138例HPV E6/E7 mRNA阳性患者≥HSIL总检出率为22.46%(31/138),16/18/45+组检出率最高(37.78%,17/45)。HPV E6/E7 mRNA阳性组发生≥HSIL的相对危险度(RR值)是HR-HPV DNA阳性组的2.246倍(95%CI为1.493～3.379);16/18/45+组发生≥HSIL的RR值是16/18+组患者的3.169倍(95%CI为1.786～5.622);HPV E6/E7 mRNA其余11型+组发生≥HSIL的RR值是HR-HPV DNA其余12型+组的2.170倍(95%CI为1.115～4.222),差异均有统计学意义(P0.05)。结论:HPV E6/E7 mRNA检测尤其是16/18/45分型检测是LBC-/HPV+患者人群发生≥HSIL的有效风险预测指标,其评价效能优于包含HPV16/18分型的HR-HPV DNA检测;HPV E6/E7 mRNA有望作为HR-HPV DNA阳性但16/18分型阴性患者的进一步分流指标。     

宫颈癌机会性筛查人群中高危型HPV感染状况及其与宫颈病变关系的研究

目的:分析宫颈癌机会性筛查人群中高危型HPV感染情况及其与宫颈病变的关系。方法:统计2015年6月至2016年11月于北京大学第三医院行宫颈癌机会性筛查人群中HPV 16型、18型及其他12种HPV亚型的阳性率,计算高危型HPV阳性转诊阴道镜人群中发生CINⅡ及以上(CINⅡ~+)的比率及CINⅡ~+人群中HPV的感染构成情况。结果:宫颈癌机会性筛查人群中,高危型HPV总阳性率为19.0%,HPV 16阳性率为5.0%,HPV 18阳性率为1.6%,其他12种HPV阳性率为15.2%。HPV 16阳性、HPV 18阳性及其他12种HPV阳性患者TCT分流检测≥ASCUS者均转诊阴道镜病理活检,其发生CINⅡ~+的比率依次为55.2%、35.5%及38.9%;发生CINⅢ及以上(CINⅢ~+)的比率依次为25.3%、7.7%及6.9%。CINⅡ~+中45.0%为其他12种HPV感染、46.3%为HPV16感染、8.7%为HPV 18感染,其余病例为HPV阴性。结论:宫颈癌机会性筛查人群中,CINⅡ~+患者HPV 18阳性所占比率较低,其他12种HPV阳性所占比率高。需对各亚型阳性率进行细致分型以协助评估发病风险。转诊阴道镜人群中,HPV 18阳性者及其他12种HPV阳性患者TCT检查为ASCUS/LSIL者发生CINⅡ~+风险相对较低,可考虑通过行分流检测以提高筛查的特异性。     

E6/E7 mRNA检测在宫颈癌高危人群HPV分流的应用

目的探讨采用E6/E7 mRNA检测方法对于CIN1及以下病变的宫颈癌高危人群HPV阳性分流的可行性。方法选择2016年1—6月山西省古交市、北京市密云县和河北省曲周县在2014年政府免费宫颈癌筛查中发现的322例诊断为宫颈上皮内病变(CIN1)及以下病变作为研究对象,进行HPV PCR分型检测,其中高危HPV阳性者再进行宫颈细胞学检查和E6/E7 mRNA检测,任一阳性者进行阴道镜检查,并对阴道镜检查可疑或异常者进行定点活检和组织病理学检查。结果 322例患者中,高危型HPV阳性检出率为34.2%(110/322),其中80例(72.7%)为单一HPV高危亚型阳性,主要感染型别前三位分别为HPV52、HPV16和HPV58。宫颈细胞学分流检出CIN2及以上病变2例(1.8%,2/110)。E6/E7 mRNA分流检出CIN2及以上病变5例,检出率为4.6%。在E6/E7 mRNA阳性患者中CIN2及以上为5例(14.3%);E6/E7 mRNA阴性患者中,CIN2及以上患者为3例(4.0%),两组比较,差异无统计学意义(P=0.066)。结论对于HPV阳性者采用E6/E7 mRNA分流宫颈癌前病变的检出率高于细胞学分流,可应用于宫颈癌高危人群HPV阳性的分流。     

HPV E6/E7 mRNA检测在宫颈癌筛查中应用价值的Meta分析

目的:评价HPV E6/E7 mRNA检测在宫颈癌筛查中的临床应用价值。方法:检索数据库并筛选英文文献,对纳入文献进行质量评估,提取纳入研究的特征信息。以宫颈组织病理诊断为金标准,研究HPV E6/E7 mRNA检测在宫颈癌筛查中应用价值的相关文献进行Meta分析。结果:共纳入10篇文献,纳入文献稳定性好,研究对象共计44477例。对参与筛查人群诊断级别CINⅡ及以上(CINⅡ~+)的宫颈病变,HPV E6/E7 mRNA检测和HPV DNA二代杂交捕获检测(HC2)的合并敏感度分别为0.89(95%CI 0.85~0.91)及0.92(95%CI 0.90~0.95);合并特异度分别为0.93(95%CI0.93~0.93)及0.90(95%CI 0.90~0.90)。诊断级别CINⅢ及以上(CINⅢ~+)的宫颈病变,两者合并敏感度无明显差异,HPV E6/E7 mRNA检测的合并特异度较高。结论:与HC2检测相比,HPV E6/E7 mRNA检测CINⅢ~+的宫颈病变表现出较高的特异度。HPV E6/E7 mRNA检测可作为宫颈癌病变启动监测指标,可提早发现高级别病变,提早进行临床干预,改善患者临床结局。     

HPV E6/E7 mRNA检测在HPV分型及宫颈疾病筛查中的作用研究

目的探讨人乳头瘤病毒(HPV)E6/E7 m RNA检测在女性宫颈疾病筛查中的作用。方法选取2016年9月至2017年9月贵州医科大学附属医院妇产科门诊和住院部就诊的HPV阳性感染者287例,其中宫颈疾病患者267例[包括宫颈炎、宫颈上皮内瘤变(CIN)Ⅰ~Ⅲ、宫颈癌],阳性感染者中体检无疾病表现及病理学检查无宫颈病变者20例。取患者宫颈脱落细胞用支链DNA技术(简称b-DNA技术)检测高危HPV E6/E7 m RNA,患者同时行宫颈液基薄层细胞检测和HPV分型检测,对不同年龄、HPV分型、阴道细胞学分型(简称TBS分型)及疾病分级的HPV E6/E7 m RNA的诊断价值进行效能分析。结果在不同年龄段内E6/E7阳性和阴性所占比例差异有统计学意义,P0.05,在年龄组≤30岁组和50~60岁组,E6/E7阳性者所占比例最大,分别为85.40%和84.40%;而HPV E6/E7m RNA拷贝数在不同年龄组内差异没有统计学意义。E6/E7结果在单一感染和混合感染,以及单一感染和多重感染间差异无统计学意义;在不同感染型别中,只有HPV 16型随病变严重程度的增加其感染率呈递增趋势(P0.05),其余HPV型与病变严重程度无明显相关性(P0.05)。不同疾病分组间,E6/E7阳性率的分布差异有统计学意义,表现为无宫颈病变组(0)宫颈炎(15.60%)CINⅠ(86.20%)CINⅡ(93.00%)CINⅢ(96.50%)宫颈癌(100.00%),P0.05;E6/E7拷贝数表达差异有统计学意义,表现为宫颈炎1773.89(936.54)CINⅠ4997.74(10 439.75)CINⅡ52 655.02(38 495.10)CINⅢ72 300.12(38 298.57)宫颈癌121 616.68(34 348.59),P0.05。结论在宫颈疾病中检测高危型HPVE6/E7 m RNA的转录对女性宫颈癌高危人群的筛查和诊治具有重要的价值,或可作为进一步分流HPV阳性病人的方法。     

TruScreen对HPV检测阳性者分流意义的研究

目的探讨在我国农村妇女宫颈癌筛查项目中,通过TruScreen(TS)和液基细胞学(LBC)对HPV阳性人群进行进一步分流的筛查效果。方法 2018年8月～12月,对9 972例参加国家农村妇女宫颈癌筛查项目的妇女进行HPV初筛,HPV16/18阳性者进行阴道镜检查,其他12种HPV高危亚型阳性者同时进行TS和LBC检查进行分流,任一结果异常者进行阴道镜检查。通过比较TS和LBC对CIN2+和CIN3+检出率,分析两种方法对HPV检测阳性者的分流效果。结果 HPV初筛阳性率为7.54%,其中HPV16/18阳性率为2.14%,其他12种HPV高危亚型阳性率为5.41%。TS和LBC分流的异常率分别是18.74%和16.70%,两种分流策略的异常率差异无统计学意义(χ~2=0.770,P=0.380)。TS和LBC分流CIN2+检出率分别为2.41%和3.71%,差异无统计学意义(χ~2=1.532,P=0.216)。TS分流和LBC分流CIN3+检出率分别为1.11%和2.23%,差异也无统计学意义(χ~2=2.034,P=0.154)。结论 TS和LBC两种分流策略对HPV阳性人群宫颈病变的检出效果无明显差异,各地区可根据自身的实际情况选择合适的分流方法。     

子宫颈液基细胞学异常患者中检测HPV E6/E7 mRNA的临床意义

目的探讨子宫颈液基细胞学(TCT)异常患者中检测人乳头状瘤病毒(human papillomavirus,HPV)E6/E7 mRNA的临床意义。方法对267例TCT异常的患者和40例TCT未见恶性细胞及上皮内瘤变细胞者(对照组)进行HPV DNA检测和HPVE6/E7 mRNA检测,以阴道镜检查病理结果为金标准。结果正常、ASCUS、低度鳞状上皮内病变(LSIL)和高度鳞状上皮内病变(HSIL)的HPVE6/E7 mRNA阳性率分别为20.00%(8/40)、27.57%(51/185)、60.87%(42/69)和76.92%(10/13)。病理诊断正常、LSIL(CIN1)、HSIL(CIN2/3和癌)的HPVE6/E7 mRNA阳性率分别为11.72%(17/145)、34.07%(31/91)、87.88%(58/66)和5/5,差异均有统计学意义(P0.05)。HPVE6/E7 mRNA对CIN2及以上(CIN2+)诊断的灵敏度88.73%(95%CI:81.38%~96.09%)高于TCT对CIN2+诊断的灵敏度22.68%(95%CI:20.19%~24.66%),HPV E6/E7 mRNA对CIN2+诊断的特异度79.66%(95%CI:74.53%~84.8.0%)低于TCT对CIN2+的特异度86.10%(95%CI:84.44%~88.32%),差异均无统计学意义(P0.05)。TCT联合和HPVE6/E7 mRNA试验筛查效果较好,灵敏度和特异度分别为85.92%(95%CI:77.8%~94.01%)和82.63%(95%CI:77.79%~87.6%)。结论 HPVE6/E7 mRNA阳性率随着病理学宫颈病变级别升高呈趋势性增加,TCT联合HPV E6/E7 mRNA检测能够提高对宫颈病变筛查的敏感性和特异性,弥补TCT筛查的不足。     

APTIMA HPV E6/E7 mRNA和MALDI-TOF-MS HPV基因分型检测宫颈高度病变效果评价

目的:以HC-Ⅱ法HPV DNA为对照,评价APTIMA法HPV E6/E7 mRNA检测(A-HPV)和MALDI-TOF-MS HPV分型检测技术(M-HPV)用于宫颈癌与癌前病变筛查的临床价值。方法:深圳市25~59岁、3年内未行宫颈癌筛查、未接受过子宫切除和盆腔放疗的2095例未孕妇女参加了本次筛查。医生于患者宫颈外口处直接收集2份宫颈脱落细胞标本,一份用于液基细胞学检查,一份用于HC-Ⅱ、A-HPV和M-HPV检测。宫颈细胞学≥ASCUS及3种方法 HPV检测任一阳性结果者均回叫行阴道镜下定点或四象限活检及宫颈管诊刮(ECC)。以病理诊断为标准评价各种HPV检测方法用于宫颈癌筛查的价值。结果:2095例研究对象中各项检测数据齐全者1970例。1970例患者的平均年龄为(35.89±7.655)岁。细胞学≥ASCUS者占6.4%(127/1970),CINⅡ+者占1.3%(26/1970),CINⅢ+者占0.76%(15/1970)。HC-Ⅱ、A-HPV和M-HPV总的HPV阳性率分别是19.4%、12.1%和14.8%,差异有统计学意义(P0.05)。HC-Ⅱ、A-HPV和M-HPV对检出CINⅡ+病变的敏感性分别为88.5%(95%CI为68.7~97.0)、100%(95%CI为84.0~100)和92.3%(95%CI为73.4~98.7),特异性分别为81.5(95%CI为79.7~83.2)、89.1%(95%CI为87.6~90.4)和86.3%(95%CI为84.6~87.8);A-HPV与HC-Ⅱ相比敏感性稍高(P0.05),M-HPV敏感性和HC-Ⅱ相同(P0.05),三者比较有统计学意义(P0.05)。结论:A-HPV和M-HPV用于宫颈癌筛查都有很好的敏感性和准确性,两者活检率明显低于HC-Ⅱ,可减少医疗负担和花费。HPV亚型分型和HPV E6/E7 mRNA结合有更好地预测宫颈癌患病风险的作用。     

HPV E6/E7 mRNA检测对ASCUS患者临床分层处理价值评价

目的:探讨HPV E6/E7 mRNA检测在意义不明确的不典型鳞状细胞(ASCUS)人群进一步处理措施中的分层管理价值。方法:对112例ASCUS患者,同时行HPV E6/E7 mRNA、HPV DNA检测以及阴道镜下活检。结果:(1)ASCUS患者宫颈活检结果分布于宫颈炎及宫颈上皮内瘤变(CIN)Ⅰ、Ⅱ、Ⅲ病变中。(2)HPV E6/E7 mRNA检测ASCUS中高级别病变的敏感性(94.44%)与HPV DNA检测相比差异无统计学意义(P0.05)。而特异性(45.74%)高于HPV DNA检测(18.89%),差异有统计学意义(P0.05)。(3)随着宫颈病变级别升高,HPV E6/E7 mRNA载量增加,且各级别病变间差异有统计学意义(P0.0083);HPV DNA载量在各级别病变中的差异无统计学意义(P0.0083)。(4)ROC曲线确定的HPV E6/E7 mRNA诊断高级别宫颈上皮内瘤变(CINⅡ~+)的最佳诊断临界点为543.64 copy/ml,曲线下面积为0.780。结论:ASCUS病理结果具有多样性,HPV E6/E7mRNA检测不仅可以检出其中的高级别宫颈病变,减少了不必要的阴道镜检查及活检,还能及时发现潜在高级别宫颈病变,避免高危患者漏诊。     

Risk assessment and clinical impact of liquid-based cytology, oncogenic human papillomavirus (HPV) DNA and mRNA testing in primary cervical cancer screening (the FASE study)

Objective

New commercial HPV RNA assays require further validation studies in population-based cervical cancer screening settings.To assess the performance of (FDA-approved) APTIMA® HPV Assay (AHPV), Hybrid Capture 2 (HC2), in-house PCR genotyping, and ThinPrep LBC in population-based screening, stratified by three histological gold standards.

Study design

A multi-center trial in 5006 women undergoing routine screening in France was designed to compare the absolute and relative risks of diagnosing CIN3 + and CIN2 + lesions by different diagnostic tests.

Results

Reproducibility between the primary and second pathology reading was excellent for CIN3 + and CIN2 + endpoints (Cohen's kappa 0.948 and 0.854). Absolute risks (PPV) of different tests (AHPV, HC2, PCR genotyping, LBC) in diagnosing CIN2 + (15-20%) and CIN3 + (4-6%) were similar for the first, second, and consensus pathology readings. The relative risks of diagnosing these lesions by the four tests were also similar when the first, second or third pathology readings were employed. AHPV had the highest absolute risk of both histological endpoints, and detects 5% to 15% more CIN3 + and CIN2 + lesions, respectively, than LBC. Compared with HC2 assay, the relative risk of AHPV is 24% to 29% higher, with a significant difference in CIN2 + detection. With LBC as reference, AHPV had the best sensitivity/specificity balance measured by AUC (area under ROC curve) comparison test (significant for CIN2 +), and the colposcopy referral rate (9.2%) comparable to that of LBC (8.7%).

Conclusions

These data corroborate the suitability of AHPV for the primary cervical cancer screening.     

HPV16 and increased risk of recurrence after treatment for CIN

OBJECTIVE: Addition of high-risk human papillomavirus (hrHPV) testing to post-treatment monitoring policies of women treated for high-grade cervical intraepithelial neoplasia (CIN) may improve the effectiveness of detecting recurrent/residual disease. Recent studies have shown that HPV type 16 confers an increased risk of high-grade CIN and cervical cancer. This study aimed to find out whether the post-treatment CIN3 rate is increased in HPV16-positive women treated for CIN3. METHODS: We included 229 hrHPV-positive women treated for CIN3. HPV typing was performed by GP5+/6+-PCR followed by reverse line blotting on a cervical scrape taken before treatment. HPV typing data were related to the occurrence of post-treatment CIN3 within a median follow-up time of 20.1 months (range 3-85.4 months) following treatment. RESULTS: Twenty nine of the 151 (19%) HPV16-positive women versus 6 of the 78 (8%) women with other hrHPV types had recurrent/residual CIN3. Post-treatment CIN3 rate was significantly increased in women with HPV16 compared to those harboring other hrHPV types (p=0.03). None of the other hrHPV types were associated with higher post-treatment CIN3 rates. CONCLUSION: Women treated for HPV16 containing CIN3 should be monitored more intensively because of their increased risk of post-treatment CIN3. Thus, the HPV genotype should be considered in post-treatment monitoring policies.     

延安市宫颈癌机会性筛查应用研究

目的探讨延安市宫颈癌机会性筛查的应用价值。方法：2012年1月至2013年9月在延安市人民医院妇科门诊就诊的患者自愿行宫颈癌机会性筛查,以液基细胞学检查、高危型人乳头瘤病毒检测和阴道镜为筛查方法,宫颈活检组织病理学结果为最终诊断标准,探讨机会性筛查对宫颈癌早期发现、早期治疗的意义。结果：3000例患者全部行TCT检查,阳性检出率为16．17％（485／3000）;3000例患者中同时行HPV检测者有1475例,感染率为25．90％（382／1475）：468例患者在阴道镜下行宫颈活检术,病理结果为：CIN I 82例、CINⅡ～Ⅲ 46例、SCC 9例。结论：通过机会性筛查可以更好地提高防治效果,对宫颈癌的早诊早治有着非常重要的意义,值得推广应用。     

Quantification of intracellular HPV E6/E7 mRNA expression increases the specificity and positive predictive value of cervical cancer screening compared to HPV DNA

Objectives

Current methods for HPV screening rely on the detection of L1 DNA from high risk genotypes (HRHPV). These assays have very high negative predictive values (~ 99%), however, the specificity and positive predictive value of HPV DNA tests for pre-cancerous and cancerous lesions (CIN 2+) is less than 50%. The purpose of this study was to compare HPV DNA with intracellular HPV E6, E7 mRNA quantification in an effort to improve the performance of cervical cancer screening.

Methods

Liquid-based cervical cytology specimens collected in either PreservCyt or SurePath were processed for routing cytology, HPV HRDNA detection by Hybrid Capture 2 and HPV E6, E7 mRNA quantification in cells using the same sample. We analyzed a total of 2049 samples including 73 with CIN 2, CIN 3, or squamous cell carcinoma by biopsy and 1694 samples from women with normal cytology.

Results

The positive predictive value of HPV E6, E7 mRNA quantification in cells for CIN2+ was 78% which was greater than HPV DNA alone (43%). The specificity of HPV E6, E7 mRNA quantification was 96% based on normal cytology compared to 82% for HC2 while the specificity of HPV E6, E7 mRNA quantification based on CIN 2− histology was 85% compared to 35% for HC2.

Conclusions

With similar sensitivity and greater specificity/positive predictive value, HPV E6, E7 mRNA quantification in cells is an improvement over HPV DNA for cervical cancer screening.     

宫颈癌机会性筛查的应用与探讨

目的:探讨宫颈癌机会性筛查的应用及意义。方法:为2008年1月~12月在新疆自治区人民医院妇产科门诊就诊的患者行机会性筛查,以液基细胞学、HPV检测和阴道镜为筛查方法,活检组织病理学诊断为最终诊断标准,评价机会性筛查用于宫颈癌早诊、早治的意义。结果:4485例患者中一半以上患者不了解宫颈癌相关知识;患者筛查顺应性为98.79%(4431/4485),检出细胞学阳性569例,阳性检出率12.68%(569/4485);561例行高危HPV检测,感染率36.54%(205/561);549例行阴道镜+活检,活检病理结果为:CINⅠ62例,CINⅡ-Ⅲ46例、SCC 8例。2008年宫颈癌筛查参与率及宫颈病变检出率与2007年同期比较差异有统计学意义(P0.05)。结论:通过机会性筛查相关干预措施有助于提高患者对宫颈癌的认知程度,是全面防治宫颈癌的重要内容;机会性筛查顺应性好,能够早期发现宫颈病变,是行之有效的宫颈癌筛查方法,值得推广应用。     

Performance of the Roche AMPLICOR human papillomavirus (HPV) test in prediction of cervical intraepithelial neoplasia (CIN) in women with abnormal PAP smear

OBJECTIVES: To assess the performance of a novel PCR-based assay (Roche AMPLICOR HPV test) in detection of cervical pathology as a part of management for abnormal PAP smear (MAPS) and in women participating in cervical cancer screening. STUDY DESIGN: Altogether, 504 women comprising 270 patients referred for colposcopy due to an abnormal Pap smear and another 234 women participating in cervical cancer screening (tested for comparison) were analyzed for oncogenic (HR) Human papillomavirus (HPV) types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68 using the Roche AMPLICOR HPV test in cervical samples collected in PreservCyt liquid media. Colposcopic biopsy and/or LEEP cone biopsy was used as the gold standard in the triage group, while liquid-based cytology (LBC) was the reference test in the screening group. RESULTS: The prevalence of HPV was significantly higher in the MAPS group (65.9%) than in the screening group (31.2%) (P = 0.0001). There was a poor concordance between the referral PAP and the current LBC, being only moderate in the screening series, ICC (weighted kappa) = 0.291 (95%CI 0.070-0.459) (P = 0.007), and almost poor in the MAPS Series, with ICC = 0.217 (95%CI 0.04-0.384) (P = 0.023). AMPLICOR HPV positivity increased linearly with the increasing grade of cervical lesions. In detecting high-grade (CIN2-3), colposcopy was the most sensitive test (96.5%), very similar to AMPLICOR (95.2%) (P = 0.731), while LBC with HSIL cutoff was by far the most specific test (99.5%) and showed the highest PPV (96.1%). NPV of colposcopy (97.2%) and AMPLICOR (96.7%) were similar (P = 0.839). Together with abnormal colposcopy and HSIL cytology, the AMPLICOR HPV test is a powerful independent predictor of high-grade CIN2-3, and as such suitable to replace cervical cytology in management of women with abnormal PAP test (MAPS). CONCLUSIONS: The Roche AMPLICOR HPV test is comparable to other HPV tests (HCII, PCR) in detecting CIN in MAPS. However, more data are clearly needed on the performance of AMPLICOR test in management of abnormal PAP and particularly as a screening tool.     

Screening for cervical cancer in high-risk populations: DNA pap test or Hybrid Capture II test alone?

This study was designed to evaluate whether Hybrid Capture II (HC2) test alone refer women to colposcopy as appropriately as DNA Papanicolaou (Pap) test, in the context of a high-risk group of women using the recently validated DNACitoliq LBC system. Women with suspected cervical disease were included in this cross-sectional study at a tertiary center in S?o Paulo, Brazil, for further workup. All women had cervical material collected for LBC and HC2 for high-risk human papillomavirus (hrHPV)-DNA test. Irrespective of cytology and HC2 results, colposcopy, and cervical biopsy when applicable, was systematically performed. All tests were performed blindly. Sensitivity, specificity, positive and negative predictive values, and overall accuracy of both methods were computed in relation to histology. A total of 1,080 women were included: 36.4% (393/1080) had ACUS+, 10.2% (110/1080) were high-grade squamous intraepithelial lesions (HSIL) or cancer. Mean age was 33.5 years. All women underwent colposcopy, and cervical biopsies were performed in 38.4% (415/1080): 33% (137/415) of the biopsies were negative, 14.4% (155/415) were low-grade squamous intraepithelial lesions (LSIL), 10.7% (116/415) were HSIL, and 0.6% (7/415) were cancer. HC2 sensitivity to diagnose biopsy-proven HSIL was 100%. Because all HSIL cases had a positive HC2 test, sensitivity could not be improved by adding LBC. Specificity and positive and negative predictive values of DNA Pap were not significantly different from HC2 test alone when considering LSIL+ histology as "gold standard" and HSIL+ histology. As a screening strategy for women with high-risk for cervical cancer, DNA Pap test does not seem to add substantially to HC2 alone in terms of appropriately referring to colposcopy.     

LEEP治疗CIN伴高危型HPV感染的临床观察

目的探讨高频电波刀电圈切除术（LEEP）治疗宫颈上皮内瘤变（CIN）伴高危型人乳头瘤病毒（HPV）感染的临床疗效。方法对116例CINⅠ～Ⅲ伴高危型HPV阳性患者进行LEEP治疗，术后3个月再次检测其宫颈HPV—DNA的负荷量，同时行阴道镜检查及宫颈活检。结果术后3个月，80％以上的CINⅠ-Ⅲ病例转为慢性炎症；宫颈HPV负荷量由术前162．81下降为1．05，转阴率47．41％，低HPV负荷组与高HPV负荷组两组之间CIN转归存在显著差异（P=0．000）。结论LEEP可以有效治疗宫颈上皮内瘤变，同时可以明显降低宫颈HPV负荷量。LEEP治疗后，宫颈病变的转归与术后高危型HPV的负荷量的高低密切相关，提示高危型HPV负荷量的检测作为CIN治疗后随访项目之一有其必要性。