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HPVTestinginWomenwithAtypicalGlandular

CytologyAdenocarcinomainsitu

(AIS)Endocervical

adenocarcinomaEndocervical

GlandularAbnormalityHPV16wasseenin~50%

endocervicaladenocarcinomaHPV18wasseenin~32%of

endocervicaladenocarcinoma,4timeshigherthan

SCCHPV18hasbeenalsolinkedto

neuroendocrinecarcinomaofthe

cervixAdenocarcinomainSitu

(AIS)Endocervical

AdenocarcinomaTBS:GlandularCell

AbnormalitiesAtypicalGlandularCells

(AGC)Favor

endocervicalFavor

endometrialAtypicalGlandularCells(AGC),favor

neoplasticFavor

endocervicalFavor

endometrialEndocervicaladenocarcinomain

situAdenocarcinoma–endocervical,endometrial,extrauterine,

NOSAdenocarcinomain

SituAdenocarcinomain

SituAdenocarcinomaTHEBETHESDASYSTEM

WEBSITEATLASAtypicalEndocervicalCellsor

Not?/NIHInterobserverReproducibility

StudyShermanetal.Cancer(CancerCytopathology)

2007;111:15–25.1188responsesfromPathologistsandCytotechnologistsHistologicFollowupbyBaselinePAPDiagnosisinWomen(30-64

yrs)Cytologic

Dx#Cases

(%)CIN2+AIS+CIN2+/AIS+

(%)Negative923,152

(95.68)25931582751 (0.30)ASC27,050 (2.80)1391391430 (5.29)LSIL9,374 (0.97)1101101111 (11.85)ASC-H1,647 (0.17)45521476 (28.90)HSIL2,019 (0.21)1204421246 (61.71)AGC2,074 (0.21)14168206 (10.08)Total965,

360 (100)69133427255 (0.75)KatkiHA,etal.J.LowerGenitalTractDisease.17:S28-35,

20132013ASCCP

GuidelineCytologyHPV

Testing5yrRisk

CIN2+RecommendManagementNegativeNegative0.27Repeattestingin5

yrsNegativePositive10Repeattestingin6-12

monthsASCNegative1.1Repeattestingin3

yrsASCPositive18Immediatecolposcopyif

>25LSILNegative5.1Repeattestingin6-12

monthsLSILPositive19Immediatecolposcopyif

>25ASC-HNegative12ImmediatecolposcopyASC-HPositive45Immediate

colposcopyHSILNegative49Immediate

colposcopyHSILPositive71Immediate

colposcopyAGCNegative2.2Immediate

colposcopyAGCPositive45Immediate

colposcopySchiffmanMandSolomonD.NewEnglJMed.369:24,

2013AClevelandClinic

StudyTheutilityofhrHPVtestingiswidelyused

intriageofwomenwithASC,butitsroleinmanagingAGCisnotfully

elucidatedClevelandClinichasimplentedreflex

hrHPVtestingonallwomenwithASC,AGC,AEC,andASC-Hsince

2001ReviewCCexperienceandassessif

reflexhrHPVtesting(HC2)canbeusefultotriagewomenwithAEC

cytology7/2001-6/2006at

CCFAllThinPrep@PapTests

(n=332,470)AGCCytology(n=591,

0.18%)ReflexhrHPVTesting

(n=387)HistopathologicFollow-up

(n=317)HPV

Positive

(n=64) HPVnegative

(n=253)Follow-up15-74months,median45

monthsHistolopathologic

Follow-UpDiagnosis#CasesRate

(%)Negative24577.3EM

Lesions123.8CIN1165.0CIN2+237.3AIS+216.6ChenLWandYangB.CancerCytopathology,114:236-11,

2008AccuracyofCytologyinWomenDiagnosedas

AGC/AECFollow-Up#CasesCIN2/AIS+RateHPVandHistology3174413.9%HPVandHistologyCytology*3874411.4%*70caseshadonlyrepeatnegativecytologyandHPVtestingwithoutcervical

biopsy/ECCBenignCIN2/AIS+RateHPV

positive244062.5%HPV

negative24941.6%HPVTestingTriaginginWomenwithAGC

CytologyChenLWandYangB.CancerCytopathology,114:236-11,

2008SensitivityandSpecificityofHPV

TestingThesensitivityofhrHPVtesting(95%CI),inwomenwithAGCcytology,is90.9%(40/44)

indetectinghighgradecervicallesions(CIN2+/AIS+)ThespecificityofhrHPVtesting(95%CI)

is91.2%

(249/273)Positiveandnegativepredictivevaluesare62.5%and98.4%

respectivelyChenLWandYangB.CancerCytopathology,114:236-11,

2008EndometrialDiseasesinWomen

withAGC

Cytology12cases(4.7%)ofeitherendometrialcomplexhyperplasia(9)orendometrioidadenocarcinoma(3)weredetectedinsubsequentEMBor

EMCAllwomenhadnegativeHPV

testingAllwomenwere>45

years8/12womenhaduterinebleeding

symptomsincludingall3casesof

adenocarcinomaChenLWandYangB.CancerCytopathology,114:236-11,

2008TwoLargeStudieson

AGCStudiesAGC

(%)#Cases

withfollow-upHPV+

(%)CIN2+/AIS+Extra-CervicalDiseasesChen&

Yang0.1938720.2%13.9%4.7%ZhaoC.et

al0.4166224.3%9.4%6.9%ChenLWandYangB.CancerCytopathology,114:236,

2008ZhaoC.etal.GynecologicOncology,114;384,

2010Pooledmeta-analysisfrom12studies

publishedEvaluatetheaccuracyofhrHPVtestinginthemanagementofwomenwithAGCtodetectunderlyingHSIL,AISor

cancerAllstudiesusingHC2HPV

testingSummaryOurstudyandothers’demonstratethatreflexHPVtestingsignificantlyenhancesthesensitivity(90%)andspecificity(75-91.2%)ofdetectingsignificantCIN2+/AIS+inwomenwithAGCcytologyAGCcytologyinHPV+womenhasahighpredictivevalue(~60%)forhighgradehistologicalabnormalityandshouldbemanagedaggressivelywithimmediate

colposcopySummaryReflexHPVtesting,incombinationwithage,canbeaguidanceforclinicalmanagementforwomenwithAGC

cytology

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