宮頸癌篩查文獻匯報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)移行帶位置的變動主要取決于柱狀上皮生長能力的優(yōu)勢，而上皮的生長受激素的影響。在年輕婦女可見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，是成熟的鱗狀上皮保護層取代子宮頸管細胞。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備細胞細胞增生而來。5精品課件二、鱗狀上皮化生

這些細胞一旦受到刺激開始分層和分化，最后分化為成熟的鱗狀上皮，根據(jù)鱗狀上皮化生過程的不同階層分為：儲備細胞增生、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胞學(xué)異常和宮頸上皮內(nèi)瘤變(CervicalIntraepi．thelialNeoplasia，CIN)。

對宮頸病變進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?shù)奶幚砜赡茉黾訉m頸癌的發(fā)病風險，抑或過度處理導(dǎo)致不必要的并發(fā)癥發(fā)生和醫(yī)療資源的浪費。

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

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

細胞學(xué)TBS分類診斷術(shù)語，按細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梯檢查細胞學(xué)——陰道鏡——組織病理學(xué)由于中國國情，對宮頸癌篩查因地區(qū)、經(jīng)濟條件、醫(yī)療資源等差異而采用不同手段，如：細胞學(xué)檢測、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、宮頸細胞學(xué)檢查結(jié)果異常（1）不典型鱗狀上皮細胞(ASC-US)；（2）不典型鱗狀上皮細胞-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）鱗狀細胞癌（SCC）；11精品課件（6）不典型腺上皮細胞（AGC）；（7）腺原位癌（AIS）；（8）腺癌；（9）巴氏分級標準中≥巴氏Ⅱb級以上的結(jié)果；（10）高危型HPV檢測結(jié)果陽性（需注明hpv檢測方法，如：hc-2法、hpv基因分型法特別是16、18型陽性、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、慢性宮頸炎長期治療無效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