宫颈癌筛查文献汇报HPV与TCTppt课件.pptx

内内容容回回顾顾一一、转转转转化化化化区区区区二二二二、鳞鳞鳞鳞状状状状上上上上皮皮皮皮化化化化生生生生三三三三、宫宫宫宫颈颈颈颈病病病病变变变变的的的的概概概概念念念念四四四四、三三三三阶阶阶阶梯梯梯梯检检检检查查查查五五五五、阴阴阴阴道道道道镜镜镜镜检检检检查查查查指指指指征征征征一一、转转化化区区(移移行行带带)原始鳞柱交界与新生鳞柱交界的宫颈段。原始鳞柱交界与新生鳞柱交界的宫颈段。原始鳞柱交界与新生鳞柱交界的宫颈段。原始鳞柱交界与新生鳞柱交界的宫颈段。原始鳞状上皮原始鳞状上皮原始鳞状上皮原始鳞状上皮原始柱状上皮原始柱状上皮原始柱状上皮原始柱状上皮原始鳞柱交界（原始鳞柱交界（原始鳞柱交界（原始鳞柱交界（OSCJOSCJOSCJOSCJ）新的鳞柱交界（新的鳞柱交界（新的鳞柱交界（新的鳞柱交界（NSCJNSCJNSCJNSCJ）转化区（转化区（转化区（转化区（TZTZTZTZ）正常转化区正常转化区正常转化区正常转化区一、转化区一、转化区(移行带移行带)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。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，通常在子宫颈的以下，绝经后妇女，移行带内移，通常在子宫颈的高处。高处。一、转化区一、转化区(移行带移行带)移行带是移行带是移行带是移行带是CINCINCINCIN和和和和宫颈宫颈宫颈宫颈CaCaCaCa的好发部位，因此细胞学的好发部位，因此细胞学的好发部位，因此细胞学的好发部位，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检查必须包括这一部位，阴道镜检查的原则之一就检查必须包括这一部位，阴道镜检查的原则之一就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。是要了解移行带的情况。是要了解移行带的情况。是要了解移行带的情况。二、鳞状上皮化生二、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。状上皮化生和鳞状上皮化生。鳞状上皮化鳞状上皮化是指成熟的鳞状上皮直接向邻近的柱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。管细胞。鳞状上皮化生鳞状上皮化生是指从子宫颈管基层膜上面具有改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向功能的储备细胞细胞增生而来。二、鳞状上皮化生二、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、成熟不同阶层分为：储备细胞增生、未成熟磷化、成熟磷化。磷化。三三、宫颈病变的概念、宫颈病变的概念广义：广义：广义：广义：宫颈病变宫颈病变(Cervicallesions)：是一个尚未限定的、：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，包括比较泛化的概念，指在宫颈区域发生的各种病变，包括炎炎炎炎症、损伤、肿瘤症、损伤、肿瘤症、损伤、肿瘤症、损伤、肿瘤(以及癌前病变以及癌前病变)、畸形和子宫内膜异位症畸形和子宫内膜异位症畸形和子宫内膜异位症畸形和子宫内膜异位症等等。Company Logo 狭义：狭义：狭义：狭义：临床上将宫颈病变限定在临床上将宫颈病变限定在宫颈细胞学异常宫颈细胞学异常宫颈细胞学异常宫颈细胞学异常和和宫颈上皮内瘤变宫颈上皮内瘤变宫颈上皮内瘤变宫颈上皮内瘤变(CervicalIntraepithelialNeoplasia，CINCIN)。对宫颈病变进行正确处理及采用合适的管理方法是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。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。度处理导致不必要的并发症发生和医疗资源的浪费。不同诊断术语的含义不同诊断术语的含义子宫颈上皮内瘤变子宫颈上皮内瘤变子宫颈上皮内瘤变子宫颈上皮内瘤变（Cervical Intraepithelial NeoplasiaCervical Intraepithelial Neoplasia，CINCIN）：组织学诊断术语，按病变细胞涉及上皮层次分组织学诊断术语，按病变细胞涉及上皮层次分为为、级。级。子宫颈鳞状上皮内病变子宫颈鳞状上皮内病变子宫颈鳞状上皮内病变子宫颈鳞状上皮内病变（Squamous intraepithelial LesionSquamous intraepithelial Lesion，SILSIL）：细胞学细胞学TBS分类诊断术语，按细胞的异型性改分类诊断术语，按细胞的异型性改变分为低度鳞状上皮内病变（变分为低度鳞状上皮内病变（LSIL）和高度鳞状）和高度鳞状上皮内病变（上皮内病变（HSIL）四、宫颈病变三阶梯检查细胞学细胞学阴道镜阴道镜组织病理学组织病理学由于中国国情，对宫颈癌筛查因地区、经济条件、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、医疗资源等差异而采用不同手段，如：细胞学检测、裸眼醋酸染色检查裸眼醋酸染色检查(VIN)(VIN)及复方碘染及复方碘染(VILI)(VILI)检查，高检查，高危型危型HPVDNAHPVDNA检查、肉眼观察高度怀疑宫颈浸润癌等，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，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，即并在阴道镜指导下完成组织病理学检查诊断，即“三阶梯三阶梯”的检查诊断。的检查诊断。五、阴道镜检查指征1 1、宫颈细胞学检查结果异常、宫颈细胞学检查结果异常、宫颈细胞学检查结果异常、宫颈细胞学检查结果异常（1 1）不典型鳞状上皮细胞）不典型鳞状上皮细胞）不典型鳞状上皮细胞）不典型鳞状上皮细胞(ASC-US)(ASC-US)；（2 2）不典型鳞状上皮细胞）不典型鳞状上皮细胞）不典型鳞状上皮细胞）不典型鳞状上皮细胞-不除外高度鳞状上不除外高度鳞状上不除外高度鳞状上不除外高度鳞状上 皮内病变（皮内病变（皮内病变（皮内病变（ASC-HASC-H）；）；）；）；（3 3）低度鳞状上皮内病变（）低度鳞状上皮内病变（）低度鳞状上皮内病变（）低度鳞状上皮内病变（LSILLSIL）；）；）；）；（4 4）高度鳞状上皮内病变（）高度鳞状上皮内病变（）高度鳞状上皮内病变（）高度鳞状上皮内病变（HSILHSIL）；）；）；）；（5 5）鳞状细胞癌（）鳞状细胞癌（）鳞状细胞癌（）鳞状细胞癌（SCCSCC）；）；）；）；（6 6）不典型腺上皮细胞（）不典型腺上皮细胞（）不典型腺上皮细胞（）不典型腺上皮细胞（AGCAGC）；）；）；）；（7 7）腺原位癌（）腺原位癌（）腺原位癌（）腺原位癌（AISAIS）；）；）；）；（8 8）腺癌；）腺癌；）腺癌；）腺癌；（9 9）巴氏分级标准中）巴氏分级标准中）巴氏分级标准中）巴氏分级标准中 巴氏巴氏巴氏巴氏bb级以上的结果；级以上的结果；级以上的结果；级以上的结果；（1010）高危型）高危型）高危型）高危型HPVHPV检测结果阳性（需注明检测结果阳性（需注明检测结果阳性（需注明检测结果阳性（需注明hpvhpv检测方法，检测方法，检测方法，检测方法，如：如：如：如：hc-2hc-2法、法、法、法、hpvhpv基因分型法特别是基因分型法特别是基因分型法特别是基因分型法特别是1616、1818型阳性、型阳性、型阳性、型阳性、PCRPCR法）法）法）法）2 2、裸眼醋酸染色或复方碘染色后肉眼观、裸眼醋酸染色或复方碘染色后肉眼观、裸眼醋酸染色或复方碘染色后肉眼观、裸眼醋酸染色或复方碘染色后肉眼观 察（察（察（察（via/vilivia/vili）结果异常。）结果异常。）结果异常。）结果异常。3 3、裸眼直观为宫颈溃疡、肿块或可疑宫、裸眼直观为宫颈溃疡、肿块或可疑宫、裸眼直观为宫颈溃疡、肿块或可疑宫、裸眼直观为宫颈溃疡、肿块或可疑宫 颈浸润癌。颈浸润癌。颈浸润癌。颈浸润癌。4 4、可疑病变处指导性活检、可疑病变处指导性活检、可疑病变处指导性活检、可疑病变处指导性活检5 5、宫颈锥切前确定病变范围、宫颈锥切前确定病变范围、宫颈锥切前确定病变范围、宫颈锥切前确定病变范围6 6、宫颈尖锐湿疣、宫颈尖锐湿疣、宫颈尖锐湿疣、宫颈尖锐湿疣7 7、慢性宫颈炎长期治疗无效、慢性宫颈炎长期治疗无效、慢性宫颈炎长期治疗无效、慢性宫颈炎长期治疗无效8 8、阴道和外阴病变：阴道和外阴上皮内瘤样变、早、阴道和外阴病变：阴道和外阴上皮内瘤样变、早、阴道和外阴病变：阴道和外阴上皮内瘤样变、早、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、尖锐湿疣等期阴道癌、阴道腺病、梅毒、结核、尖锐湿疣等期阴道癌、阴道腺病、梅毒、结核、尖锐湿疣等期阴道癌、阴道腺病、梅毒、结核、尖锐湿疣等July3,2018questionDoescervicalcancerscreeningusingprimary cervical human papillomavirus(HPV)testing comparedwithcytologyresultinalowerlikelihoodofcervicalintraepithelialneoplasiagrade3orworse(CIN3+)at48months?Importance Thereislimitedinformationabouttherelativeeffectivenessofcervicalcancerscreeningwithprimary human papillomavirus(HPV)testing alone comparedwithcytologyinNorthAmericanpopulations.OBJECTIVE Toevaluatehistologicallyconfirmedcumulativeincidentcervicalintraepithelialneoplasia(CIN)grade 3 or worse(CIN3+)detectedup to and including 48 monthsbyprimary HPV testing alone(intervention)or liquid-based cytology(control).Methods TheprimaryobjectiveofthisstudywastoevaluateprimaryHPVtestingforcervicalcancerscreeninginanorganizedprogramsetting.PARTICIPANTS InclusioncriteriawerewomeninBritishColumbia,Canada,withapersonalhealthnumber,aged25to65yearswhohadnothadaPapanicolaoutestintheprevious12months,werenotpregnant,werenotHIVpositiveorreceivingimmunosuppressivetherapy,andhadnohistoryofCIN2+inthepast5years;didnothaveinvasivecervicalcancer;ordidnothavetotalhysterectomy.Womenwhometinclusioncriteriaandwerepatientsof224collaboratingcliniciansinMetroVancouverandGreaterVictoriawereinvitedtoparticipate.Randomization Womenwererandomlyassigned1:1:1to1of3(intervention,control,or safety)groupsbetweenJanuary2008andDecember31,2010.StartingJanuary1,2011,womenwereassigned1:1totheinterventionorcontrolwhenthesafetygroupwasclosed.Womenandclinicianswereblindedtogroupassignmentuntil24monthsorifthebaselinescreenresultswerepositiveandrequiredfollow-up.Theprimaryanalysisforthisstudyfocusesontheinterventionandcontrolgroups.Interventions ParticipantsrandomizedtoHPV testing alone(intervention group)withnegativetestresultswererecalledat48 months forexitwithHPVandLBCtesting.ParticipantsrandomizedtoLBC testing(control group)withnegativetestresultswereaskedtoreturnat24 months forrepeattestingwithLBCinaccordancewiththecervicalcancerscreeningguidelinesinBritishColumbia.IfLBCresultswerenegativeatthis24-monthscreen,participantswereaskedtoreturnat48 months forexitwithHPVandLBCtesting.Intervention GroupPrimaryHPVtestingwasfollowedbyreflexLBCinwomenwithpositive HPV testresults.Atbaseline,ifHPVpositiveandLBCnegative,womenwererecalledin12 months forHPVandLBCtesting.At12months,ifwomenwereeitherHPVorLBCpositive(atypicalsquamouscellsofundeterminedsignificanceASCUS),theywerereferredforcolposcopy.IfbothHPVandLBCnegativeat12months,theywererecommendedforexitscreen at 48 months.IfthebaselinereflexLBCresultwasgreaterthanorequaltoASCUS,theywerereferredforimmediate colposcopy andmanagement.Control GroupPrimaryLBCtestingwasfollowedbyreflexHPVtestingforwomenwithASCUS.IfASCUSandHPVpositiveatbaseline,womenwerereferredforimmediatecolposcopy.WomenwithASCUSandHPV-negativebaselineresultswererecalledforLBCagainat12 months andwerereferredforcolposcopyiftheirLBCresultwasgreaterthanorequaltoASCUS.WomenwithbaselineLBClow-gradesquamousintraepitheliallesionsorgreaterresultswerereferredforcolposcopy and management.Safety Group PrimaryHPVtestingwasfollowedbyreflexLBCinwomenwithpositiveHPVtestresults,andtheyreceivedthesamemanagementastheinterventiongroup.However,inthesafetygroup,HPV-negativewomenwererecalledforexitscreeningwithLBCat24months.ThesafetygroupwasclosedDecember31,2010,whentheplannedsamplesizeforthisgroupwasachieved.INTERVENTION AND CONTROL GROUP EXIT SCREENING Exitscreeningforboththeinterventionandcontrolgroupsoccurred48monthsafterbaselinescreeningandconsistedofHPVtestingandLBC(exitco-testing).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.Themaintrialobjectivewastocomparetheratesofcervicalintraepithelialneoplasia(CIN)grade3orgreater(CIN3+)48monthsafterbaselinescreeningwithprimaryHPVvsLBC.Detailedtrialmethodsandresultshavebeenpreviouslydescribed.AsoutlinedinFigure1,round1referstothebaselinescreenandany12-monthfollow-upresultsinboththeinterventionandcontrolgroups.The24-monthscreenroundrefersonlytowomeninthecontrolgroupbecausetheinterventiongroupdidnotreceive24-monthscreening,andthis24-monthscreenroundincluded24-monthscreenresultsand36-monthfollow-upresults.The48-monthexitroundrefersto48-monthexitscreeningresults(plus24-monthresultsforthecontrolgroup)andassociatedoutcomesforboththeinterventionandcontrolgroupsTrial Outcomes Primary end points：RatesofCIN3+at48monthsintheinterventionandcontrolgroups.Secondary trial end included in this analysis：ratesofCIN2+at48months,thethresholdforcolposcopyreferralandfurtherevaluation,andevaluationoftheimpactofprimaryHPVtestingoncolposcopyservicesthroughevaluationofcolposcopyreferralratesineachgroup.Othersecondaryendpointsnot included inthisanalysis：histologicallyconfirmedCIN2+detectedat2yearsinboththecontrolandsafetygroups;clearanceofHPVinfectioninwomenwhowerebaselineHPVpositivemeasuredat24and48months;detectionofhistologicallyconfirmedCIN3+inHPV-positivewomenwhoreceived12-monthretestingmeasuredat24monthsinthesafetygroup;andtotalestimatedcostperwomanscreenedandtotalestimatedcostperquality-adjustedlife-yeargainedforeachtechnologymeasuredat48months.AllinterventionandcontrolgroupwomenwhodidnothaveaCIN2+lesiondetectedduringthetrialorotherwisebecameineligible(eg,hysterectomy,movedoutofprovince)wereinvitedforthe48-monthexitscreening.WomenwhowerenegativeonbothLBCandHPVco-testingat48monthsweredeemednegativeforCIN2+.WomenwhowereeitherLBCofgreaterthanorequaltoASCUSorHPVpositiveat48monthswerereferredforcolposcopyandbiopsiedtodeterminetheirstatusasCIN3+,CIN2+,lessthanorequaltoCIN1,ornormal.Results Primary End Points AmongbaselineHPVorLBC-negativewomen,ratesofCIN3+at48monthsweresignificantlyhigheracrossallagegroupsinthecontrolcomparedwiththeinterventiongroup(Table2).CumulativeincidencecurvesshowthatwomenwhowereHPVnegativeatbaselinehadasignificantlylowerriskofCIN3+at48monthscomparedwithcytology-negativewomen.Secondary End Points Inthefirstroundofscreening,significantlymoreCIN2+casesweredetectedintheinterventiongroup(HPVtested)comparedwiththecontrolgroup.CumulativeCIN2+incidencecurvesshownosignificantlydifferentdiseasedetectionacrosstrialgroups.Intheinterventiongroup,cumulativeincidencewashigherearlierinthetrialat18and42monthscomparedwiththecontrolgroup.Inthistrial,allwomenintheinterventionandcontrolgroupshadthesameinterventionatthe48-monthexit(HPVandcytologyco-testing).Bytheendoftrialfollow-up(72months),incidencewassimilaracrossbothgroups.Among19009womenwhowererandomized(meanage,45years10th-90thpercentile,30-59),16374(829686.9%intheinterventiongroupand807885.4%inthecontrolgroup)completedthestudy.At48months,significantly fewer CIN3+and CIN2+weredetectedintheinterventionvscontrolgroup.Discussion Inthistrial,by48months,amongwomenscreenedforcervicalcancerwithHPVtestingwithoutcytology,thereweresignificantlyfewerCIN3+andCIN2+casescomparedwithwomenwhowerescreenedwithcytologyaloneatbaseline.WomenwhowereHPVnegativeatbaselineweresignificantlylesslikelytohaveCIN3+andCIN2+at48monthscomparedwithwomenwhowerecytologynegativeatbaseline.TheseresultshavedemonstratedthatprimaryHPVtestingdetectscervicalneoplasiaearlierandmoreaccuratelythancytology.AlthoughcervicalscreeningguidelinesfromanumberoforganizationshaverecommendedprimaryHPVtestingbasedonthenaturalhistoryofcervicalcancer,cross-sectionalstudies,18studieswhereHPV-basedscreeningwaspartofascreeninggroup,orwherestudiesultimatelyevolvedintoprimaryHPVevaluations,noneofthesestudiesweredesignedspecificallytoexamineHPVtestingastheprimaryscreeningmodality.Thistrial,whichcomparesprimaryHPVtestingvsLBCwithstandardizedtriageandcolposcopyfollow-up,foundprimaryHPVtestingdetectedsignificantlymoreCIN3+andCIN2+casesinthefirstroundandsignificantlyreducedCIN3+andCIN2+rates48monthslater.ThistrialalsoconfirmedthatwomenwhowereHPVnegativeatbaselinehavelowerratesofCIN2+at48monthsthancytology-negativewomenatbaseline.PreviousstudiesfoundthebenefitofHPVandcytologyco-testingwasbasedprimarilyonthecontributionofHPV,21whichthistrialnowprospectivelyvalidates.Furtheranalysesmodelingthecost-effectivenessofHPVprimaryscreeningusingparametersfromthisstudywillbecarriedouttoassessthepotentialeconomiceffectofmovingtoHPV-basedscreeningConclusions Amongwomenundergoingcervicalcancerscreening,theuseofprimaryHPVtestingcomparedwithcytologytestingresultedinasignificantlylowerlikelihoodofCIN3+at48months.Furtherresearchisneededtounderstandlong-termclinicaloutcomesaswellascost-effectiveness.THANKTHANKTHANKTHANK YOU!YOU!YOU!YOU!