金域大數(shù)據(jù)引發(fā)的宮頸癌篩查思考

從金域大樣本檢測數(shù)據(jù)引發(fā)的宮頸癌篩查思考金域?qū)m頸病變檢測中心孫宜M.D.&Ph.D

16,115,000金域檢驗宮頸癌篩查至今例次宮頸細胞學：1260萬高危型HPV病毒檢測：351.5萬CAP質(zhì)控體系和方法、分析和統(tǒng)計金域數(shù)據(jù)-論文發(fā)表：10篇分別在：2016年5月剛被“

JournalofCancer”接收2016年3月在“AmJClinPathol”《美國臨床病理雜志》2015年7月在“CancerCytopathology”《癌癥細胞病理》2015年3月在”JournaloftheAmericanSocietyofCytopathology”《美國細胞病理學》2015年3月在”ArchivesofPathologyandLaboratoryMedicine”《病理學與實驗室醫(yī)學檔案》

《國際細胞學雜志》、《實用腫瘤學雜志》、《中國癌癥防治雜志》、《BMC傳染病學雜志》….金域數(shù)據(jù)-墻報展示：9篇分別在：2016年4月在ASCCP年會、2016年3月在USCAP年會2014年和2015年USCAP年會PrevalenceandgenotypedistributionofHPVInfectioninChina:analysisof51,345HPVgenotypingresultsfromChina’slargestCAPcertifiedlaboratoryZhengyuZeng,HuaitaoYang,ZaiboLi,XuekuiHe,ChristopherC.Griffith,XiamenChen,XiaoleiGuo,BaowenZheng,ShangweiWu,ChengquanZhao中國人群HPV感染率和基因型的研究：來自中國最大CAP認可實驗室的51345例HPV送檢標本結(jié)果分析曾征宇；楊懷濤；李再波；何學魁；ChristopherC.Griffith；陳顯梅；郭曉磊；鄭寶文；吳尚為；趙澄泉2016年5月，剛被“

JournalofCancer”接收2016年2月發(fā)表在AmJClinPathol《美國臨床病理雜志》PrevalenceofHigh-RiskHumanPapillomavirusInfectioninChina，Analysisof671,163HumanPapillomavirusTestResultsFromChina’sLargestCollegeofAmericanPathologists-CertifiedLaboratoryZhengyuZeng,MD；R.MarshallAustin,MD,PhD；XuekuiHe；XianmeiChen,MD；XiaoleiGuo；BaowenZheng,MD；ShangweiWu,MD,PhD；HuaitaoYang,MD,PhD；ChengquanZhao,MD中國人群高危型HPV感染率的研究--來自CAP認可的中國最大實驗室的671,163例HPV檢測結(jié)果曾征宇；AustinM;何學奎；陳顯梅；郭曉磊；鄭寶文；吳尚為；楊懷濤；趙澄泉AmericanJournalofClinicalPathologyAdvanceAccesspublishedMarch2,2016GovernmentsupportedCPScervicalscreeningisbeingintroducedinruralareasofChinasuchasHainanProvince.TheinternationalCAPLAPhasprovidedlaboratoryqualitycontrolstandardsnototherwisereadilyavailableinmanyunderservedinternationalsettings.ReportingrateswerewithinCAPbenchmarkrangesfordifferentTBScategories,exceptforlowreportingratesforunsatisfactorysmearsandforAGC;educationaltrainingprogramshavebeeninstitutedtoaddresstheseissues.ResultsConclusionDesignBackground70%oftheChinesepopulationresidesinruralareas,where90%ofincidentcervicalcancercasesareestimatedtooccurandwherecervicalcancerscreeningisstilluncommonduetothefinancialrestraints.TheChinesegovernmenthasintroducedcervicalscreeningprograminruralareas.Thiswasaretrospectivestudytosummarizecervicalscreeningresultsin11ruralcountiesinHainanProvidence.Thewomenvolunteeredtoattendscreening.Mostofthewomenwerepreviouslyunscreened.TheconventionalPapspecimens(CPS)werecollectedsenttotheCAPcertifiedGuangzhouCytologyLaboratoryforslidepreparationandreview.TheTBSreportratesamongthedifferentyearswereshowninTable1.Thereportedabnormalratewas4.4%ofallwomen,withHSILreportedin0.5%.Abnormalcytologyratesvariedamongcounties.Intermsofagegroups,theLSILreportingratewassignificantlyhigherinwomen<50yearsthanyoungerwomen(1.04%vs0.64%).TheHSILreportingratewassignificantlyhigherinwomen≥40yearsthanyoungers(5.3%vs0.38%)(Table2).2286womenwithabnormalPapsmearshadcolposcopicandhistopathologicfollowupwithin3monthsaftertheabnormalPaptests.Cervicalcancer,CIN2/3,andCIN1wereidentifiedin1.0%,22%,and56%women,respectively(table3).2016ASCCPANNUALMEETING,NewOrleansConventionalPapSmearCervicalScreeningin11RuralCountiesinHainanProvidence,China:AnalysisofTBSReportingRatesFor218,195ScreenedWomen

BaowenZheng1,MarshallAustin2,XiaomanLiang1,HuanWan1,GuijianWei1,YaomingLiang1,ChengquanZhao21.GuangzhouKingmedDiagnosticsguangzhou,China2.DepartmentofPathology,Magee-Women'sHospitalofUPMC,Pittsburgh,PATable2TBSreportingrateindifferentagegroups(11counties)CategoryAge2011201220132014TotalASC-US(%)44.9941（2.88）1318（2.47）1866（2.73）1519（2.37）5644（2.6）ASC-H(%)48.191（0.28）164（0.31）219（0.32）234（0.37）708（0.3）LSIL(%)43.3299（0.92）380（0.71）743（1.09）563（0.88）1985（0.9）HSIL(%)46.3199（0.61）223（0.42）341（0.50）316（0.49）1079（0.5）SCC(%)51.410（0.03）002（0.003）12（0.01）AGC(%)44.709（0.02）6（0.01）14（0.02）29（0.01）NILM(%)45.331116（95.28）51168（96.07）64972（95.18）60891（95.12）208147（95.7）Unsat(%)44.401（0）114（0.17）476（0.74）591（0.3）Total45.932656532636826164015218195Table1.TBSreportingratebyyearsin11CountiesTable2TBSreportingrateindifferentagegroups(11counties)AgesASC-US(%)ASC-H(%)LSIL(%)HSIL(%)SCC(%)AGC(%)NILM(%)Unsatisfactory(%)Total20-2954（1.75）10（0.32）34（1.10）4（0.13）002971（96.06）20（0.65）309330-391399（2.49）119（0.21）595（1.06）221（0.39）1（0.002）5（0.009）53670（95.53）171（0.30）5618140-492504（2.86）247（0.28）902（1.03）462（0.53）4（0.005）20（0.022）83315（95.05）198（0.23）8765250-591296（2.40）259（0.48）348（0.64）287（0.63）6（0.011）4（0.007）51611（95.63）158（0.29）53969>=60260（2.34）58（0.52）66（0.59）68（0.61）1（0.009）010626（95.58）38（0.34）11117Unknown131（2.12）15（0.24）40（0.65）37（0.60）005954（96.30）6（0.10）6183Total5644（2.59）708（0.32）1985（0.91）1079（0.49）12（0.006）29（0.01）208147（95.39）591（0.27）218195CPSCategoryNegative%CIN1%CIN2/3%SCC%ADC%TotalASC-US342(29.8)700(60.9)103(9.0)4(0.35)01149LSIL69(11.2)479(77.9)67(10.9)00615ASC-H43(20.3)66(31.1)96(45.3)4(1.9)3(1.4)212HSIL9(3.0)43(14.2)243(79.9)7(2.3)2(0.66)304AGC01(16.7)2(33.3)03(50)6Total463(20.3)1289(56.4)511(22.4)15(0.66)8(0.35)2286Table3.SurgicalFollow-upresults.(Cancer23/2286=1.01%)Reportsofhighriskhumanpapillomavirus(hrHPV)testingpatternsandpositiveratesindifferentcytologicalcategoriesfromChinaarerare.WeevaluatedtestingpatternsandpositiveratesindifferentcytologicalcategoriesinChina'slargestCAP-accreditedlaboratory.MethodsConclusionsHighRiskHPVTestingandReportRate:ResultfromtheLargestCAPCertifiedIndependentLaboratoryinChinaBaowenZheng1,ZaiboLi2,ZhenyuZeng1,CongdeChen1,JaYou1,LingyunTan1,ChengquanZhao31.GuangzhouKingmedDiagnostics,Guangzhou,China,2.DepartmentofPathology,OhioStateUniversityMedicalCenter,Columbus,OH,3.DepartmentofPathology,Magee-Women'sHospitalofUPMC,Pittsburgh,PALogoThehrHPV-positiveratewas35%inpatientswithASC-US,with40%inpatientsyoungerthan30yearsand34.1%inpatientswithanageof30yearsorolder.ThehrHPV-positiveratewas12.1%inpatientswithNILM,with14.6%inpatientsyoungerthan30yearsand11.5%inpatientswithanageof30yearsorolder.TheoverallhrHPV-positiverateswere77.7%inLSIL,90.5%inHSILand80.8%inASC-Hand47%inAGC.ThehrHPV-positiveratewassimilarinvariousliquid-basedcytologymethodsincludingThinPrep,SurePath,LITOUliquid-basedpreparation,buthigherinconventionalandLIPUpreparations.ThisisthefirstroutineclinicalpracticereportofhrHPVpositiveratesinvariablePapcytologycategoriesinChina.ThehrHPV-positiveratereportedfromChina‘slargestCAP-accreditedlaboratorywascomparabletothatreportedamongUSlaboratories(HumanPapillomavirusTestingandReportingRatesin2012,ResultsofaCollegeofAmericanPathologistsNationalSurvey,ArchPatholLabMed2015;139:757–761).Therefore,participationintheinternationalCAPLaboratoryAccreditationProgramprovideslaboratoryqualitystandardsnototherwiseavailableinmanyinternationalsettings.HPVpositiverateis12%inwomenwithnegativePaptest,muchhigherthanthatinmostreportsintheWesterncountries

(??),indicatinghigherprevalenceofhrHPVinfectioninGuangdong,China.BackgroundResultsLogoResultsfrom128,195PapanicolaoutestswithhrHPVtestingbyHybridCapture2(HC2),renderedbetweenJanuary2011andDecember2014bytheGuangzhouKingMedDiagnosticsCytologyLaboratory,wereanalyzed.ThesamplesforPaptestandHPVtestweresavedintwodifferentvials.Categories<30years>=30yearsTotalCase#Positive(%)Case#Positive(%)Case#Positive(%)AgesASC-US2,425970(40.0)11,239

3,827(34.1)13,6644,797(35.1)37.8（16-80）LSIL1,3251,032(77.9)4,339

3,367(77.6)5,6644,399(77.7)35.8（15-93）ASC-H6343(69.3)671550(82.0)734593(80.8)43.7（23-80）HSIL7864(82.1)11571,054(91.1)12351,118(90.5)42.5（16-80）AGC126(50.0)12257(46.7)13463(47.0)41.5（28-64）NILM19,2372807(14.6)87,52710,065(11.5)106,76412,872(12.1)xxTotal23,1404922(21.3)105,05518,920(18.0)128,19523,842(18.6)xxTable1.HRHPVPositiveRatesinWomenwithVariousPapTestResults.PreparationThinPrepSurePathCPTLITUOLIPUCase#92,45818,0304,2188,7394,609HPVPositive#17,1673,1911,0701,5871,098Positiverate18.6%17.7%26.4%18.2%23.8%Table2.HRHPVPositiveRatesinVariousPreparationMethods.2016AnnualMeetingofUnitedStates&CanadaAcademyofPathology(USCAP),Seattle,WAOf8446patientswithhistologicallydiagnosedCIN2/3overa48-monthperiod,3342patients(averageage39.0,19-77years)hadpriorHC2hrHPVtestingand/orPaptestresultsincluding1657withpriorhrHPVtesting(average1.3months;0.5-9months)and2369withpriorPapcytology(average1.5months;0.5-11months)beforehistologicaldiagnosis.ThehrHPV-negativeratewas8.8%(145of1657patients)andthePap-negativeratewas6.6%(158/2396)(p=0.01).ThenegativePapratewassignificantlydifferentdependingonthepreparation,highestinLiqui-PrepandlowestinLituo.AbnormalPaptestresultsarelistedintable1.Of711patientswithbothHPVandPaptestingresults,62(8.7%)

hadnegativePapcytologyand50(7.0%)hadnegativeHPVtesting(p=0.23).Only16(2.3%)haddoublenegativeresults.Table1.PriorPapcytologyresultsin2396womenwithCIN2/3onhistologyKruskal-WallisP<0.0001PriorPaptestand/orHPVtestingresultsin3342womenwithhistologicallydiagnosedcervicalintraepithelialneoplasia2/3:datafromChina’slargestCAPcertifiedclinicallaboratoryTaoWu1,ChristopherC.Griffith2,BaowenZheng1,XiangdongDing1,YaomingLiang1,ChengquanZhao31.DepartmentofPathology,KingMedDiagnostics,Guangzhou,China,2.DepartmentofPathology,EmoryUniversity,Atlanta,GA3.DepartmentofPathology,Magee-Women'sHospitalofUPMC,Pittsburgh,PA2016AnnualMeetingofUnitedStates&CanadaAcademyofPathology(USCAP),Seattle,WAHighgradesquamouslesionscausedbypersistenthrHPVinfectionareregardedasprecursortocervicalcancer.ThisstudyweexaminePapcytologyandhrHPVtestingresultsprecedinghistologicdiagnosesofCIN2/3inChina.BackgroundDesignThisstudydemonstratesrelativelyhighpriornegativetestingresultswithbothhrHPVandPapcytologyinapopulationofwomenwithCIN2/3inChinawherethereisnonationalcancerscreeningprogramorcervicalcytologyqualitycontrolstandards.hrHPVtestingwasnotmoresensitivethanPapcytologyindetectionofhighgradesquamouslesion.PatientshavingbothpriorHPVandcytologyhadlowerratesofdoublenegativeresults,supportingthevalueofcontestingtoenhancedetectionofcervicalcancerprecursors.ConclusionsCasesofCIN2/3diagnosedfrom2011to2014byhistologywereretrievedfromPathologydepartment.PriorhrHPVandPapcytologyresultsintheyearbeforeCIN2/3diagnoseswererecorded.ResultsCategoryThinPrepSurePathLiqui-PrepLituoConventionalTotalHSIL514(42.1)108(48.6)31(36.5)244(51.7)173(43.7)1070(44.7)LSIL231(18.9)61(27.5)16(18.8)109(23.1)83(21.0)500(20.9)ASC-H192(15.7)17(7.7)14(16.5)64(13.6)67(16.9)354(14.8)ASC-US176(14.4)20(9.0)11(12.9)42(8.9)54(13.6)303(12.6)AGC8(0.7)1(0.5)01(0.2)1(0.3)11(0.5)Negative100(8.2)15(6.8)13(15.3)12(2.5)18(4.5)158(6.6)Total1221222854723962396CategoryHPVPositiveHPVNegativeTotalN%N%N%HSIL27241.191828139.5LSIL14622.161215221.4ASC-H8412.76129012.7ASC-US11016.6132612317.3AGC30.50030.4Negative467.01632628.7Total66110050100711100Table2.PriorPapandHPVtestresultsin711womenhavingbothtests2014USCAPANNUALMEETINGSan

Diego,CA數(shù)據(jù)分析細胞學檢測&組織學結(jié)果比對高危型HPV檢測&組織學結(jié)果比對細胞學聯(lián)合病毒學檢測&組織學結(jié)果比對細胞學檢測結(jié)果數(shù)據(jù)分析

陽性檢出率HSIL檢出率HSIL陽性預(yù)測值金域集團2015年3,738,962例宮頸細胞學檢測結(jié)果TBS分類液基涂片傳統(tǒng)涂片合計（例）例%例%不滿意305541.1275320.7438086ASCUS1044533.83218332.15126286ASC-H68190.2522740.229093LSIL412011.5168150.6748016HSIL151000.5530410.3018141SCC3980.01360.00434AGC11910.041840.021375總檢測例數(shù)2,725,6501001,013,3121003,738,962陽性檢出169,1626.21%41,7154.12%210,877陽性檢出率：液基細胞學--6.21%傳統(tǒng)涂片--4.12%HSIL檢出率：液基細胞學--0.55%傳統(tǒng)涂片--0.30%廣東省2014年12縣市99,573人農(nóng)村兩癌篩查

陽性檢出率:7.98%

HSIL檢出率1.01%液基細胞學海南省11縣市農(nóng)村218,195人宮頸癌篩查（2011~2014）

陽性檢出率4.35%HSIL檢出率0.5%

傳統(tǒng)涂片癌前病變HSIL檢出率傳統(tǒng)涂片液基細胞學CAP中位數(shù)（2012）CAP中位數(shù)（2012）金域2,725,650例（2015）廣東省99,573人農(nóng)村篩查（2014）金域1,013,312例（2015）海南省218,195例農(nóng)村篩查（2011-2014）細胞學檢出HSIL的比例，明顯高于CAP中位數(shù)

廣州金域HSIL的陽性預(yù)測值PPV>80%

HSIL中檢出癌比例3.5~4.8~10.1%

資料檢測例數(shù)HSIL活檢例數(shù)CIN2~3例數(shù)（%）癌例數(shù)（%）PPV（%）2007~2013*180410824141750（72.5）244（10.1）82.62014廣東農(nóng)村篩查99573312238（76.3）15（4.8）81.12012~2013海南農(nóng)村篩查155082171141（82.5）6（3.5）86HSIL中檢出癌前病變和癌的比例高細胞學檢查的陽性檢出率較高HSIL檢出率較高（CAP)HSIL結(jié)果中，活檢證實癌前病變和癌的比例較高細胞學檢查陽性預(yù)測值（PPV）高宮頸癌的細胞學檢查，檢出率高宮頸細胞學的質(zhì)量控制好（PPV>80%)宮頸細胞學在宮頸癌篩查中的作用不可替代結(jié)果：金域的數(shù)據(jù)結(jié)論：高危型HPV病毒學檢測結(jié)果數(shù)據(jù)分析廣州金域（2007-2014）671,163例高危型HPV檢測結(jié)果分析

高危型HPV陽性檢出率：21.4%PrevalenceandgenotypedistributionofHPVInfectioninChina:analysisof51,345HPVgenotypingresultsfromChina’slargestCAPcertifiedlaboratory

高危型HPV感染率前三的型別：52、16、58Categories<30years>=30yearsTotalCase#Positive(%)Case#Positive(%)Case#Positive(%)AgesASC-US2,425970(40.0)11,239

3,827(34.1)13,6644,797(35.1)37.8（16-80）LSIL1,3251,032(77.9)4,339

3,367(77.6)5,6644,399(77.7)35.8（15-93）ASC-H6343(69.3)671550(82.0)734593(80.8)43.7（23-80）HSIL7864(82.1)11571,054(91.1)12351,118(90.5)42.5（16-80）AGC126(50.0)12257(46.7)13463(47.0)41.5（28-64）NILM19,2372807(14.6)87,52710,065(11.5)106,76412,872(12.1)xxTotal23,1404922(21.3)105,05518,920(19.0)128,19523,842(18.6)xx廣州金域128,195例不同細胞學結(jié)果中高危型HPV陽性率細胞學結(jié)果，并未見上皮病變（NILM）中，高危型HPV陽性率12.1%HSIL的高危型HPV陽性率最高，而在腺細胞病變中HPV陽性率較低廣州金域427例宮頸癌病例的HPV檢測結(jié)果（2011-2014.10)檢測例數(shù)平均年齡（范圍）HPV（+）（%）HPV-（%）42745.6(23-81)395（92.5）32（7.5）427例浸潤性子宮頸癌診斷前高危型HPV檢測與宮頸細胞學檢查結(jié)果分析，《癌癥細胞病理》雜志，2015-7思考：1、如何處理

12%hr-HPV+,（NILM）的病人？復(fù)檢／陰道鏡（病人管理)2、如何發(fā)現(xiàn)10%HSIL,20%ASC-H,而

hr-HPV(-)的病人？(donothing?->

SCC,undertreatment)3、如何發(fā)現(xiàn)>50%AGC,而hr-HPV(-)的病人？(donothing?–>AIS,Adenocarcinoma?undertreatment)3、如何早期發(fā)現(xiàn)7.5%

已經(jīng)是宮頸癌,而hr-HPV依然(-)的病人？宮頸癌中HPV的陰性率：7.5%高危型HPV陽性檢出率較高宮頸癌和癌前病變中存在不少hr-HPV陰性的病例(upto20%)結(jié)果：結(jié)論：高危型HPV檢測

很好，檢出較多陽性人群它也可會漏掉不少癌癥和癌前病變hr-HPVtest不等于PapTest;不可替代Paptest二者互相補充，應(yīng)該進行聯(lián)合篩查若在經(jīng)濟落后的地區(qū)，PapTest更便宜細胞學聯(lián)合病毒學檢測結(jié)果分析宮頸癌病例中的陰性率CIN2、CIN3中的陰性率

細胞學HPV檢測細胞學+HPV聯(lián)合檢測陽性152140154陰性（%）3（1.9%）15（9.7%）1（0.6%）在115例宮頸癌病例中，細胞學檢查，陰性率為1.9%HPV檢測，陰性率為9.7%細胞學+HPV檢測,

陰性率

0.6%結(jié)論：聯(lián)合檢測是最好的篩查方法155例宮頸癌病例中細胞學和HPV檢測的結(jié)果CategoryHPVPositiveHPVNegativeTotalN%N%N%HSIL27241.191828139.5LS