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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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