內容回顧一、轉化區二、鱗狀上皮化生三、宮頸病變的概念四、三階梯檢查五、陰道鏡檢查指征宮頸癌篩查文獻匯報HPV與TCT一、轉化區(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轉化區（TZ）⑥正常轉化區宮頸癌篩查文獻匯報HPV與TCT一、轉化區(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外口以下，絕經后婦女，移行帶內移，通常在子宮頸的高處。宮頸癌篩查文獻匯報HPV與TCT一、轉化區(移行帶)

移行帶是CIN和宮頸Ca的好發部位，因此細胞學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。宮頸癌篩查文獻匯報HPV與TCT

二、鱗狀上皮化生

柱狀上皮轉化為鱗狀上皮存在兩種不同轉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。宮頸癌篩查文獻匯報HPV與TCT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。宮頸癌篩查文獻匯報HPV與TCT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，指在宮頸區域發生的各種病變，包括炎癥、損傷、腫瘤(以及癌前病變)、畸形和子宮內膜異位癥等。宮頸癌篩查文獻匯報HPV與TCTCompanyLogo

狹義：臨床上將宮頸病變限定在宮頸細胞學異常和宮頸上皮內瘤變(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鍵的組成部分。不適當的處理可能增加宮頸癌的發病風險，抑或過度處理導致不必要的并發癥發生和醫療資源的浪費。

宮頸癌篩查文獻匯報HPV與TCT不同診斷術語的含義子宮頸上皮內瘤變（CervicalIntraepithelialNeoplasia，CIN）：

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

細胞學TBS分類診斷術語，按細胞的異型性改變分為低度鱗狀上皮內病變（LSIL）和高度鱗狀上皮內病變（HSIL）

宮頸癌篩查文獻匯報HPV與TCT四、宮頸病變三階梯檢查細胞學——陰道鏡——組織病理學由于中國國情，對宮頸癌篩查因地區、經濟條件、醫療資源等差異而采用不同手段，如：細胞學檢測、裸眼醋酸染色檢查(VIN)及復方碘染(VILI)檢查，高危型HPVDNA檢查、肉眼觀察高度懷疑宮頸浸潤癌等，這些篩查結果異常者，需轉診陰道鏡檢查和診斷，并在陰道鏡指導下完成組織病理學檢查診斷，即“三階梯”的檢查診斷。宮頸癌篩查文獻匯報HPV與TCT五、陰道鏡檢查指征1、宮頸細胞學檢查結果異常（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病變（ASC-H）；（3）低度鱗狀上皮內病變（LSIL）；（4）高度鱗狀上皮內病變（HSIL）；（5）鱗狀細胞癌（SCC）；宮頸癌篩查文獻匯報HPV與TCT（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級以上的結果；（10）高危型HPV檢測結果陽性（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）宮頸癌篩查文獻匯報HPV與TCT2、裸眼醋酸染色或復方碘染色后肉眼觀察（via/vili）結果異常。3、裸眼直觀為宮頸潰瘍、腫塊或可疑宮頸浸潤癌。4、可疑病變處指導性活檢宮頸癌篩查文獻匯報HPV與TCT5、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：陰道和外陰上皮內瘤樣變、早期陰道癌、陰道腺病、梅毒、結核、尖銳濕疣等宮頸癌篩查文獻匯報HPV與TCTJuly

3,

2018宮頸癌篩查文獻匯報HPV與TCTquestionDoes

cervical

cancer

screening

using

primary

cervicalhumanpapillomavirus(HPV)testingcomparedwithcytologyresultinalowerlikelihoodofcervicalintraepithelialneoplasiagrade3orworse(CIN3+)at48months?宮頸癌篩查文獻匯報HPV與TCTImportance

Thereislimitedinformationabouttherelativeeffectivenessofcervicalcancerscreeningwithprimaryhumanpapillomavirus(HPV)testingalonecomparedwithcytologyinNorthAmericanpopulations.Objective

To

evaluate

histologically

confirmed

cumulative

incident

cervical

intraepithelialneoplasia(CIN)grade3orworse(CIN3+)detecteduptoandincluding48monthsbyprimaryHPVtestingalone(intervention)orliquid-basedcytology(control).宮頸癌篩查文獻匯報HPV與TCTMethods

TheprimaryobjectiveofthisstudywastoevaluateprimaryHPVtestingforcervicalcancerscreeninginanorganizedprogramsetting.Participants

InclusioncriteriawerewomeninBritishColumbia,Canada,withapersonalhealthnumber,aged25to65yearswhohadnothadaPapanicolaoutestintheprevious12months,werenotpregnant,werenotHIVpositiveorreceivingimmunosuppressivetherapy,andhadnohistoryofCIN2+inthepast5years;didnothaveinvasivecervicalcancer;ordidnothavetotalhysterectomy.Womenwhometinclusioncriteriaandwerepatientsof224collaboratingcliniciansinMetroVancouverandGreaterVictoriawereinvitedtoparticipate.宮頸癌篩查文獻匯報HPV與TCTRandomization

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

Womenandclinicianswereblindedtogroupassignmentuntil24monthsorifthebaselinescreenresultswerepositiveandrequiredfollow-up.Theprimaryanalysisforthisstudyfocusesontheinterventionandcontrolgroups.宮頸癌篩查文獻匯報HPV與TCTInterventions

ParticipantsrandomizedtoHPVtestingalone(interventiongroup)withnegativetestresultswererecalledat48monthsforexitwithHPVandLBCtesting.ParticipantsrandomizedtoLBCtesting(controlgroup)withnegativetestresultswereaskedtoreturnat24monthsforrepeattestingwithLBCinaccordancewiththecervicalcancerscreeningguidelinesinBritishColumbia.IfLBCresultswerenegativeatthis24-monthscreen,participantswereaskedtoreturnat48monthsforexitwithHPVandLBCtesting.宮頸癌篩查文獻匯報HPV與TCTInterventionGroupPrimaryHPVtestingwasfollowedbyreflexLBCinwomenwithpositiveHPVtestresults.Atbaseline,ifHPVpositiveandLBCnegative,womenwererecalledin12monthsforHPVandLBCtesting.At12months,ifwomenwereeitherHPVorLBCpositive(≥atypicalsquamouscellsofundeterminedsignificance[ASCUS]),theywerereferredforcolposcopy.IfbothHPVandLBCnegativeat12months,theywererecommendedforexitscreenat48months.IfthebaselinereflexLBCresultwasgreaterthanorequaltoASCUS,theywerereferredforimmediatecolposcopyandmanagement.宮頸癌篩查文獻匯報HPV與TCTControlGroupPrimaryLBCtestingwasfollowedbyreflexHPVtestingforwomenwithASCUS.IfASCUSandHPVpositiveatbaseline,womenwerereferredforimmediatecolposcopy.WomenwithASCUSandHPV-negativebaselineresultswererecalledforLBCagainat12monthsandwerereferredforcolposcopyiftheirLBCresultwasgreaterthanorequaltoASCUS.WomenwithbaselineLBClow-gradesquamousintraepitheliallesionsorgreaterresultswerereferredforcolposcopyandmanagement.宮頸癌篩查文獻匯報HPV與TCTSafetyGroupPrimaryHPVtestingwasfollowedbyreflexLBCinwomenwithpositiveHPVtestresults,andtheyreceivedthesamemanagementastheinterventiongroup.However,inthesafetygroup,HPV-negativewomenwererecalledforexitscreeningwithLBCat24months.ThesafetygroupwasclosedDecember31,2010,whentheplannedsamplesizeforthisgroupwasachieved.InterventionandControlGroupExitScreeningExitscreeningforboththeinterventionandcontrolgroupsoccurred48monthsafterbaselinescreeningandconsistedofHPVtestingandLBC(exitco-testing).宮頸癌篩查文獻匯報HPV與TCTproceduresCompleteademographicandbehavioralquestionnaireAfter2010,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.宮頸癌篩查文獻匯報HPV與TCTThemaintrialobjectivewastocomparetheratesofcervicalintraepithelialneoplasia(CIN)grade3orgreater(CIN3+)48monthsafterbaselinescreeningwithprimaryHPVvsLBC.Detailedtrialmethodsandresultshavebeenpreviouslydescribed.

AsoutlinedinFigure1,round1referstothebaselinescreenandany12-monthfollow-upresultsinboththeinterventionandcontrolgroups.The24-monthscreenroundrefersonlytowomeninthecontrolgroupbecausetheinterventiongroupdidnotreceive24-monthscreening,andthis24-monthscreenroundincluded24-monthscreenresultsand36-monthfollow-upresults.The48-monthexitroundrefersto48-monthexitscreeningresults(plus24-monthresultsforthecontrolgroup)andassociatedoutcomesforboththeinterventionandcontrolgroups宮頸癌篩查文獻匯報HPV與TCT?宮頸癌篩查文獻匯報HPV與TCTTrialOutcomesPrimaryendpoints：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.宮頸癌篩查文獻匯報HPV與TCTResults

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.宮頸癌篩查文獻匯報HPV與TCT?宮頸癌篩查文獻匯報HPV與TCTAmong

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.宮頸癌篩查文獻匯報HPV與TCTDiscussionInthistrial,by48months,amongwomenscreenedforcervicalcancerwithHPVtestingwithoutcytology,thereweresignificantlyfewerCIN3+andCIN2+casescomparedwithwomenwhowerescreenedwithcytologyaloneatbaseline.WomenwhowereHPVnegativeatbaselineweresignificantlylesslikelytohaveCIN3+andCIN2+at48monthscomparedwithwomenwhowerecytologynegativeatbaseline.TheseresultshavedemonstratedthatprimaryHPVtestingdetectscervicalneoplasiaearlierandmoreaccuratelythancytology.Althoughcervicalscreeningguidelinesfromanumberoforganizations

haverecommendedprimaryHPVtestingbasedonthenaturalhistoryofcervicalcancer,cross-sectionalstudies,18studieswhereHPV-basedscreeningwaspartofascreeninggroup,orwherestudiesultimatelyevolved