宫颈癌筛查文献汇报HPV与TCT

内容回顾一、转化区二、鳞状上皮化生三、宫颈病变的概念四、三阶梯检查五、阴道镜检查指征1精品课件一、转化区(移行带)原始鳞柱交界与新生鳞柱交界的宫颈段。①原始鳞状上皮②原始柱状上皮③原始鳞柱交界（OSCJ）④新的鳞柱交界（NSCJ）⑤转化区（TZ）⑥正常转化区2精品课件一、转化区(移行带)移行带位置的变动主要取决于柱状上皮生长能力的优势，而上皮的生长受激素的影响。在年轻妇女可见鳞柱交界的部位多位于解剖学外口以下，绝经后妇女，移行带内移，通常在子宫颈的高处。3精品课件一、转化区(移行带)

移行带是CIN和宫颈Ca的好发部位，因此细胞学检查必须包括这一部位，阴道镜检查的原则之一就是要了解移行带的情况。4精品课件

二、鳞状上皮化生

柱状上皮转化为鳞状上皮存在两种不同转化机制即鳞状上皮化生和鳞状上皮化生。鳞状上皮化――是指成熟的鳞状上皮直接向邻近的柱状上皮内生长，是成熟的鳞状上皮保护层取代子宫颈管细胞。鳞状上皮化生――是指从子宫颈管基层膜上面具有改向功能的储备细胞细胞增生而来。5精品课件二、鳞状上皮化生

这些细胞一旦受到刺激开始分层和分化，最后分化为成熟的鳞状上皮，根据鳞状上皮化生过程的不同阶层分为：储备细胞增生、未成熟磷化、成熟磷化。6精品课件三、宫颈病变的概念广义：宫颈病变(Cervicallesions)：是一个尚未限定的、比较泛化的概念，指在宫颈区域发生的各种病变，包括炎症、损伤、肿瘤(以及癌前病变)、畸形和子宫内膜异位症等。7精品课件CompanyLogo

狭义：临床上将宫颈病变限定在宫颈细胞学异常和宫颈上皮内瘤变(CervicalIntraepi．thelialNeoplasia，CIN)。

对宫颈病变进行正确处理及采用合适的管理方法是宫颈癌防治体系中关键的组成部分。不适当的处理可能增加宫颈癌的发病风险，抑或过度处理导致不必要的并发症发生和医疗资源的浪费。

8精品课件不同诊断术语的含义子宫颈上皮内瘤变（CervicalIntraepithelialNeoplasia，CIN）：

组织学诊断术语，按病变细胞涉及上皮层次分为Ⅰ、Ⅱ、Ⅲ级。子宫颈鳞状上皮内病变（SquamousintraepithelialLesion，SIL）：

细胞学TBS分类诊断术语，按细胞的异型性改变分为低度鳞状上皮内病变（LSIL）和高度鳞状上皮内病变（HSIL）

9精品课件四、宫颈病变三阶梯检查细胞学——阴道镜——组织病理学由于中国国情，对宫颈癌筛查因地区、经济条件、医疗资源等差异而采用不同手段，如：细胞学检测、裸眼醋酸染色检查(VIN)及复方碘染(VILI)检查，高危型HPVDNA检查、肉眼观察高度怀疑宫颈浸润癌等，这些筛查结果异常者，需转诊阴道镜检查和诊断，并在阴道镜指导下完成组织病理学检查诊断，即“三阶梯”的检查诊断。10精品课件五、阴道镜检查指征1、宫颈细胞学检查结果异常（1）不典型鳞状上皮细胞(ASC-US)；（2）不典型鳞状上皮细胞-不除外高度鳞状上皮内病变（ASC-H）；（3）低度鳞状上皮内病变（LSIL）；（4）高度鳞状上皮内病变（HSIL）；（5）鳞状细胞癌（SCC）；11精品课件（6）不典型腺上皮细胞（AGC）；（7）腺原位癌（AIS）；（8）腺癌；（9）巴氏分级标准中≥巴氏Ⅱb级以上的结果；（10）高危型HPV检测结果阳性（需注明hpv检测方法，如：hc-2法、hpv基因分型法特别是16、18型阳性、PCR法）12精品课件2、裸眼醋酸染色或复方碘染色后肉眼观察（via/vili）结果异常。3、裸眼直观为宫颈溃疡、肿块或可疑宫颈浸润癌。4、可疑病变处指导性活检13精品课件5、宫颈锥切前确定病变范围6、宫颈尖锐湿疣7、慢性宫颈炎长期治疗无效8、阴道和外阴病变：阴道和外阴上皮内瘤样变、早期阴道癌、阴道腺病、梅毒、结核、尖锐湿疣等14精品课件July

3,

201815精品课件questionDoes

cervical

cancer

screening

using

primary

cervicalhumanpapillomavirus(HPV)testingcomparedwithcytologyresultinalowerlikelihoodofcervicalintraepithelialneoplasiagrade3orworse(CIN3+)at48months?16精品课件Importance

Thereislimitedinformationabouttherelativeeffectivenessofcervicalcancerscreeningwithprimaryhumanpapillomavirus(HPV)testingalonecomparedwithcytologyinNorthAmericanpopulations.Objective

To

evaluate

histologically

confirmed

cumulative

incident

cervical

intraepithelialneoplasia(CIN)grade3orworse(CIN3+)detecteduptoandincluding48monthsbyprimaryHPVtestingalone(intervention)orliquid-basedcytology(control).17精品课件Methods

TheprimaryobjectiveofthisstudywastoevaluateprimaryHPVtestingforcervicalcancerscreeninginanorganizedprogramsetting.Participants

InclusioncriteriawerewomeninBritishColumbia,Canada,withapersonalhealthnumber,aged25to65yearswhohadnothadaPapanicolaoutestintheprevious12months,werenotpregnant,werenotHIVpositiveorreceivingimmunosuppressivetherapy,andhadnohistoryofCIN2+inthepast5years;didnothaveinvasivecervicalcancer;ordidnothavetotalhysterectomy.Womenwhometinclusioncriteriaandwerepatientsof224collaboratingcliniciansinMetroVancouverandGreaterVictoriawereinvitedtoparticipate.18精品课件Randomization

Womenwererandomlyassigned1:1:1to1of3(intervention,control,orsafety)groupsbetweenJanuary2008andDecember31,2010.StartingJanuary1,2011,womenwereassigned1:1totheinterventionorcontrolwhenthesafetygroupwasclosed.

Womenandclinicianswereblindedtogroupassignmentuntil24monthsorifthebaselinescreenresultswerepositiveandrequiredfollow-up.Theprimaryanalysisforthisstudyfocusesontheinterventionandcontrolgroups.19精品课件Interventions

ParticipantsrandomizedtoHPVtestingalone(interventiongroup)withnegativetestresultswererecalledat48monthsforexitwithHPVandLBCtesting.ParticipantsrandomizedtoLBCtesting(controlgroup)withnegativetestresultswereaskedtoreturnat24monthsforrepeattestingwithLBCinaccordancewiththecervicalcancerscreeningguidelinesinBritishColumbia.IfLBCresultswerenegativeatthis24-monthscreen,participantswereaskedtoreturnat48monthsforexitwithHPVandLBCtesting.20精品课件InterventionGroupPrimaryHPVtestingwasfollowedbyreflexLBCinwomenwithpositiveHPVtestresults.Atbaseline,ifHPVpositiveandLBCnegative,womenwererecalledin12monthsforHPVandLBCtesting.At12months,ifwomenwereeitherHPVorLBCpositive(≥atypicalsquamouscellsofundeterminedsignificance[ASCUS]),theywerereferredforcolposcopy.IfbothHPVandLBCnegativeat12months,theywererecommendedforexitscreenat48months.IfthebaselinereflexLBCresultwasgreaterthanorequaltoASCUS,theywerereferredforimmediatecolposcopyandmanagement.21精品课件ControlGroupPrimaryLBCtestingwasfollowedbyreflexHPVtestingforwomenwithASCUS.IfASCUSandHPVpositiveatbaseline,womenwerereferredforimmediatecolposcopy.WomenwithASCUSandHPV-negativebaselineresultswererecalledforLBCagainat12monthsandwerereferredforcolposcopyiftheirLBCresultwasgreaterthanorequaltoASCUS.WomenwithbaselineLBClow-gradesquamousintraepitheliallesionsorgreaterresultswerereferredforcolposcopyandmanagement.22精品课件SafetyGroupPrimaryHPVtestingwasfollowedbyreflexLBCinwomenwithpositiveHPVtestresults,andtheyreceivedthesamemanagementastheinterventiongroup.However,inthesafetygroup,HPV-negativewomenwererecalledforexitscreeningwithLBCat24months.ThesafetygroupwasclosedDecember31,2010,whentheplannedsamplesizeforthisgroupwasachieved.InterventionandControlGroupExitScreeningExitscreeningforboththeinterventionandcontrolgroupsoccurred48monthsafterbaselinescreeningandconsistedofHPVtestingandLBC(exitco-testing).23精品课件proceduresCompleteademographicandbehavioralquestionnaireAfter2010,womencompletedanabbreviatedsurveypelvicexaminationHPVtestingwasperformedwiththeHybridCapture2HighRiskHPVDNAtest(Qiagen),whichdetectshigh-riskHPVtypes16,18,31,33,35,39,45,51,52,56,58,59,and68.Toconfirmspecimenadequacy,461sequentialThinPrepspecimenswithvalidHC2results(34HC2positiveand427negative)weretestedwithanin-housebeta-globinpolymerasechainreactiontestandallwerepositive.Aspartofthetrialprotocol,sampleswithnovisiblecellpelletafterconversionwererejectedasinadequate.LBCslideswerepreparedusingtheThinPrep2000(Hologic)processorandsmearswerescreenedmanuallybyprogramcytotechnologists.Abnormalcytologytestresultswerereferredtoacytopathologistforfinalinterpretationandreporting.24精品课件Themaintrialobjectivewastocomparetheratesofcervicalintraepithelialneoplasia(CIN)grade3orgreater(CIN3+)48monthsafterbaselinescreeningwithprimaryHPVvsLBC.Detailedtrialmethodsandresultshavebeenpreviouslydescribed.

AsoutlinedinFigure1,round1referstothebaselinescreenandany12-monthfollow-upresultsinboththeinterventionandcontrolgroups.The24-monthscreenroundrefersonlytowomeninthecontrolgroupbecausetheinterventiongroupdidnotreceive24-monthscreening,andthis24-monthscreenroundincluded24-monthscreenresultsand36-monthfollow-upresults.The48-monthexitroundrefersto48-monthexitscreeningresults(plus24-monthresultsforthecontrolgroup)andassociatedoutcomesforboththeinterventionandcontrolgroups25精品课件26精品课件TrialOutcomesPrimaryendpoints：RatesofCIN3+at48monthsintheinterventionandcontrolgroups.Secondarytrialend

includedinthisanalysis：ratesofCIN2+at48months,thethresholdforcolposcopyreferralandfurtherevaluation,andevaluationoftheimpactofprimaryHPVtestingoncolposcopyservicesthroughevaluationofcolposcopyreferralratesineachgroup.Othersecondaryendpoints

notincludedinthisanalysis：histologicallyconfirmedCIN2+detectedat2yearsinboththecontrolandsafetygroups;clearanceofHPVinfectioninwomenwhowerebaselineHPVpositivemeasuredat24and48months;detectionofhistologicallyconfirmedCIN3+inHPV-positivewomenwhoreceived12-monthretestingmeasuredat24monthsinthesafetygroup;andtotalestimatedcostperwomanscreenedandtotalestimatedcostperquality-adjustedlife-yeargainedforeachtechnologymeasuredat48months.AllinterventionandcontrolgroupwomenwhodidnothaveaCIN2+lesiondetectedduringthetrialorotherwisebecameineligible(eg,hysterectomy,movedoutofprovince)wereinvitedforthe48-monthexitscreening.WomenwhowerenegativeonbothLBCandHPVco-testingat48monthsweredeemednegativeforCIN2+.WomenwhowereeitherLBCofgreaterthanorequaltoASCUSorHPVpositiveat48monthswerereferredforcolposcopyandbiopsiedtodeterminetheirstatusasCIN3+,CIN2+,lessthanorequaltoCIN1,ornormal.27精品课件Results

PrimaryEndPointsAmongbaselineHPVorLBC-negativewomen,ratesofCIN3+at48monthsweresignificantlyhigheracrossallagegroupsinthecontrolcomparedwiththeinterventiongroup(Table2).CumulativeincidencecurvesshowthatwomenwhowereHPVnegativeatbaselinehadasignificantlylowerriskofCIN3+at48monthscomparedwithcytology-negativewomen.SecondaryEndPointsInthefirstroundofscreening,significantlymoreCIN2+casesweredetectedintheinterventiongroup(HPVtested)comparedwiththecontrolgroup.CumulativeCIN2+incidencecurvesshownosignificantlydifferentdiseasedetectionacrosstrialgroups.Intheinterventiongroup,cumulativeincidencewashigherearlierinthetrialat18and42monthscomparedwiththecontrolgroup.Inthistrial,allwomenintheinterventionandcontrolgroupshadthesameinterventionatthe48-monthexit(HPVandcytologyco-testing).Bytheendoftrialfollow-up(72months),incidencewassimilaracrossbothgroups.28精品课件29精品课件Among

19

009

women

who

were

randomized(meanage,

45

years[10th-90thpercentile,30-59]),16374(8296[86.9%]intheinterventiongroupand8078[85.4%]inthecontrolgroup)completedthestudy.At48months,significantlyfewerCIN3+andCIN2+weredetectedintheinterventionvscontrolgroup.30精品课件DiscussionInthistrial,by48months,amongwomenscreenedforcervicalcancerwithHPVtestingwithoutcytology,thereweresignificantlyfewerCIN3+andCIN2+casescomparedwithwomenwhowerescreenedwithcytologyaloneatbaseline.WomenwhowereHPVnegativeatbaselineweresignificantlylesslikelytohaveCIN3+andCIN2+at48monthscomparedwithwomenwhowerecytologynegativeatbaseline.TheseresultshavedemonstratedthatprimaryHPVtestingdetectscervicalneoplasiaearlierandmoreaccuratelythancytology.Althoughcervicalscreeningguidelinesfromanumberoforganizations

haverecommendedprimaryHPVtestingbasedonthenaturalhistoryofcervicalcancer,cross-sectionalstudies,18studieswhereHPV-basedscreeningwaspartofascreeninggroup,orwherestudiesultimatelyevolvedintoprimaryHPVevaluations,noneofthesestudiesweredesi