宮頸癌篩查文獻(xiàn)匯報(bào)HPV與TCT

內(nèi)容回顧一、轉(zhuǎn)化區(qū)二、鱗狀上皮化生三、宮頸病變的概念四、三階梯檢查五、陰道鏡檢查指征1精品課件一、轉(zhuǎn)化區(qū)(移行帶)原始鱗柱交界與新生鱗柱交界的宮頸段。①原始鱗狀上皮②原始柱狀上皮③原始鱗柱交界（OSCJ）④新的鱗柱交界（NSCJ）⑤轉(zhuǎn)化區(qū)（TZ）⑥正常轉(zhuǎn)化區(qū)2精品課件一、轉(zhuǎn)化區(qū)(移行帶)移行帶位置的變動(dòng)主要取決于柱狀上皮生長(zhǎng)能力的優(yōu)勢(shì)，而上皮的生長(zhǎng)受激素的影響。在年輕婦女可見(jiàn)鱗柱交界的部位多位于解剖學(xué)外口以下，絕經(jīng)后婦女，移行帶內(nèi)移，通常在子宮頸的高處。3精品課件一、轉(zhuǎn)化區(qū)(移行帶)

移行帶是CIN和宮頸Ca的好發(fā)部位，因此細(xì)胞學(xué)檢查必須包括這一部位，陰道鏡檢查的原則之一就是要了解移行帶的情況。4精品課件

二、鱗狀上皮化生

柱狀上皮轉(zhuǎn)化為鱗狀上皮存在兩種不同轉(zhuǎn)化機(jī)制即鱗狀上皮化生和鱗狀上皮化生。鱗狀上皮化――是指成熟的鱗狀上皮直接向鄰近的柱狀上皮內(nèi)生長(zhǎng)，是成熟的鱗狀上皮保護(hù)層取代子宮頸管細(xì)胞。鱗狀上皮化生――是指從子宮頸管基層膜上面具有改向功能的儲(chǔ)備細(xì)胞細(xì)胞增生而來(lái)。5精品課件二、鱗狀上皮化生

這些細(xì)胞一旦受到刺激開(kāi)始分層和分化，最后分化為成熟的鱗狀上皮，根據(jù)鱗狀上皮化生過(guò)程的不同階層分為：儲(chǔ)備細(xì)胞增生、未成熟磷化、成熟磷化。6精品課件三、宮頸病變的概念廣義：宮頸病變(Cervicallesions)：是一個(gè)尚未限定的、比較泛化的概念，指在宮頸區(qū)域發(fā)生的各種病變，包括炎癥、損傷、腫瘤(以及癌前病變)、畸形和子宮內(nèi)膜異位癥等。7精品課件CompanyLogo

狹義：臨床上將宮頸病變限定在宮頸細(xì)胞學(xué)異常和宮頸上皮內(nèi)瘤變(CervicalIntraepi．thelialNeoplasia，CIN)。

對(duì)宮頸病變進(jìn)行正確處理及采用合適的管理方法是宮頸癌防治體系中關(guān)鍵的組成部分。不適當(dāng)?shù)奶幚砜赡茉黾訉m頸癌的發(fā)病風(fēng)險(xiǎn)，抑或過(guò)度處理導(dǎo)致不必要的并發(fā)癥發(fā)生和醫(yī)療資源的浪費(fèi)。

8精品課件不同診斷術(shù)語(yǔ)的含義子宮頸上皮內(nèi)瘤變（CervicalIntraepithelialNeoplasia，CIN）：

組織學(xué)診斷術(shù)語(yǔ)，按病變細(xì)胞涉及上皮層次分為Ⅰ、Ⅱ、Ⅲ級(jí)。子宮頸鱗狀上皮內(nèi)病變（SquamousintraepithelialLesion，SIL）：

細(xì)胞學(xué)TBS分類診斷術(shù)語(yǔ)，按細(xì)胞的異型性改變分為低度鱗狀上皮內(nèi)病變（LSIL）和高度鱗狀上皮內(nèi)病變（HSIL）

9精品課件四、宮頸病變?nèi)A梯檢查細(xì)胞學(xué)——陰道鏡——組織病理學(xué)由于中國(guó)國(guó)情，對(duì)宮頸癌篩查因地區(qū)、經(jīng)濟(jì)條件、醫(yī)療資源等差異而采用不同手段，如：細(xì)胞學(xué)檢測(cè)、裸眼醋酸染色檢查(VIN)及復(fù)方碘染(VILI)檢查，高危型HPVDNA檢查、肉眼觀察高度懷疑宮頸浸潤(rùn)癌等，這些篩查結(jié)果異常者，需轉(zhuǎn)診陰道鏡檢查和診斷，并在陰道鏡指導(dǎo)下完成組織病理學(xué)檢查診斷，即“三階梯”的檢查診斷。10精品課件五、陰道鏡檢查指征1、宮頸細(xì)胞學(xué)檢查結(jié)果異常（1）不典型鱗狀上皮細(xì)胞(ASC-US)；（2）不典型鱗狀上皮細(xì)胞-不除外高度鱗狀上皮內(nèi)病變（ASC-H）；（3）低度鱗狀上皮內(nèi)病變（LSIL）；（4）高度鱗狀上皮內(nèi)病變（HSIL）；（5）鱗狀細(xì)胞癌（SCC）；11精品課件（6）不典型腺上皮細(xì)胞（AGC）；（7）腺原位癌（AIS）；（8）腺癌；（9）巴氏分級(jí)標(biāo)準(zhǔn)中≥巴氏Ⅱb級(jí)以上的結(jié)果；（10）高危型HPV檢測(cè)結(jié)果陽(yáng)性（需注明hpv檢測(cè)方法，如：hc-2法、hpv基因分型法特別是16、18型陽(yáng)性、PCR法）12精品課件2、裸眼醋酸染色或復(fù)方碘染色后肉眼觀察（via/vili）結(jié)果異常。3、裸眼直觀為宮頸潰瘍、腫塊或可疑宮頸浸潤(rùn)癌。4、可疑病變處指導(dǎo)性活檢13精品課件5、宮頸錐切前確定病變范圍6、宮頸尖銳濕疣7、慢性宮頸炎長(zhǎng)期治療無(wú)效8、陰道和外陰病變：陰道和外陰上皮內(nèi)瘤樣變、早期陰道癌、陰道腺病、梅毒、結(jié)核、尖銳濕疣等14精品課件July

3,

201815精品課件questionDoes

cervical

cancer

screening

using

primary

cervicalhumanpapillomavirus(HPV)testingcomparedwithcytologyresultinalowerlikelihoodofcervicalintraepithelialneoplasiagrade3orworse(CIN3+)at48months?16精品課件Importance

Thereislimitedinformationabouttherelativeeffectivenessofcervicalcancerscreeningwithprimaryhumanpapillomavirus(HPV)testingalonecomparedwithcytologyinNorthAmericanpopulations.Objective

To

evaluate

histologically

confirmed

cumulative

incident

cervical

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

TheprimaryobjectiveofthisstudywastoevaluateprimaryHPVtestingforcervicalcancerscreeninginanorganizedprogramsetting.Participants

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

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

Womenandclinicianswereblindedtogroupassignmentuntil24monthsorifthebaselinescreenresultswerepositiveandrequiredfollow-up.Theprimaryanalysisforthisstudyfocusesontheinterventionandcontrolgroups.19精品課件Interventions

ParticipantsrandomizedtoHPVtestingalone(interventiongroup)withnegativetestresultswererecalledat48monthsforexitwithHPVandLBCtesting.ParticipantsrandomizedtoLBCtesting(controlgroup)withnegativetestresultswereaskedtoreturnat24monthsforrepeattestingwithLBCinaccordancewiththecervicalcancerscreeningguidelinesinBritishColumbia.IfLBCresultswerenegativeatthis24-monthscreen,participantswereaskedtoreturnat48monthsforexitwithHPVandLBCtesting.20精品課件InterventionGroupPrimaryHPVtestingwasfollowedbyreflexLBCinwomenwithpositiveHPVtestresults.Atbaseline,ifHPVpositiveandLBCnegative,womenwererecalledin12monthsforHPVandLBCtesting.At12months,ifwomenwereeitherHPVorLBCpositive(≥atypicalsquamouscellsofundeterminedsignificance[ASCUS]),theywerereferredforcolposcopy.IfbothHPVandLBCnegativeat12months,theywererecommendedforexitscreenat48months.IfthebaselinereflexLBCresultwasgreaterthanorequaltoASCUS,theywerereferredforimmediatecolposcopyandmanagement.21精品課件ControlGroupPrimaryLBCtestingwasfollowedbyreflexHPVtestingforwomenwithASCUS.IfASCUSandHPVpositiveatbaseline,womenwerereferredforimmediatecolposcopy.WomenwithASCUSandHPV-negativebaselineresultswererecalledforLBCagainat12monthsandwerereferredforcolposcopyiftheirLBCresultwasgreaterthanorequaltoASCUS.WomenwithbaselineLBClow-gradesquamousintraepitheliallesionsorgreaterresultswerereferredforcolposcopyandmanagement.22精品課件SafetyGroupPrimaryHPVtestingwasfollowedbyreflexLBCinwomenwithpositiveHPVtestresults,andtheyreceivedthesamemanagementastheinterventiongroup.However,inthesafetygroup,HPV-negativewomenwererecalledforexitscreeningwithLBCat24months.ThesafetygroupwasclosedDecember31,2010,whentheplannedsamplesizeforthisgroupwasachieved.InterventionandControlGroupExitScreeningExitscreeningforboththeinterventionandcontrolgroupsoccurred48monthsafterbaselinescreeningandconsistedofHPVtestingandLBC(exitco-testing).23精品課件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精品課件Themaintrialobjectivewastocomparetheratesofcervicalintraepithelialneoplasia(CIN)grade3orgreater(CIN3+)48monthsafterbaselinescreeningwithprimaryHPVvsLBC.Detailedtrialmethodsandresultshavebeenpreviouslydescribed.

AsoutlinedinFigure1,round1referstothebaselinescreenandany12-monthfollow-upresultsinboththeinterventionandcontrolgroups.The24-monthscreenroundrefersonlytowomeninthecontrolgroupbecausetheinterventiongroupdidnotreceive24-monthscreening,andthis24-monthscreenroundincluded24-monthscreenresultsand36-monthfollow-upresults.The48-monthexitroundrefersto48-monthexitscreeningresults(plus24-monthresultsforthecontrolgroup)andassociatedoutcomesforboththeinterventionandcontrolgroups25精品課件?26精品課件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精品課件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精品課件?29精品課件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精品課件DiscussionInthistrial,by48months,amongwomenscreenedforcervicalcancerwithHPVtestingwithoutcytology,thereweresignificantlyfewerCIN3+andCIN2+casescomparedwithwomenwhowerescreenedwithcytologyaloneatbaseline.WomenwhowereHPVnegativeatbaselineweresignificantlylesslikelytohaveCIN3+andCIN2+at48monthscomparedwithwomenwhowerecytologynegativeatbaseline.TheseresultshavedemonstratedthatprimaryHPVtestingdetectscervicalneoplasiaearlierandmoreaccuratelythancytology.Althoughcervicalscreeningguidelinesfromanumberoforganizations

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