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SOGC/SCCClinicalPracticeGuideline
ColposcopicManagementofAbnormalCervicalCancerScreeningandHistology
TheseClinicalPracticeGuidelineshavebeenpreparedandapprovedbytheExecutiveandCounciloftheSocietyofCanadianColposcopists(SCC).TheseguidelineshavebeenapprovedbytheSOGC/GOC/SCCPolicyandPractice
GuidelinesCommittee,theSocietyofGynecologicOncologyofCanada(GOC)andtheExecutiveandCounciloftheSocietyofObstetriciansandGynaecologistsofCanada.
PrincipalAuthorJamesBentley,MBChB,Halifax,NS
TheExecutiveCounciloftheSocietyOfCanadianColposcopistsJamesBentley,MBChB,Halifax,NSMoniqueBertrand,MD,London,ONLizabethBrydon,MD,Regina,SKHeleneGagne,MD,Ottawa,ONBrianHauck,MD,Calgary,AB
Marie-HeleneMayrand,MD,Montreal,QCSusanMcFaul,MD,Ottawa,ONPattiPower,MD,St.John’s,NL
AlexandraSchepanski,MD,Edmonton,AB
SpecialContributorsLucyGilbert,MD,Montreal,QCJillNation,MD,Calgary,AB
MichaelShier,MD,Toronto,ONLauretteGeldenhuys,MD,Halifax,NSLindaKapusta,MD,Mississauga,ONTerryColgan,MD,Toronto,ON
RobertaHowlett,PhD,StThomas,ONJoanMurphy,MD,Toronto,ONRachelKupets,MD,Toronto,ON
DISCLOSURESTATEMENT
Disclosurestatementshavebeenreceivedfromallmembersofthecommittee(s).
DISCLAIMER
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Thisdocumentreflectsemergingclinicalandscientificadvancesonthedateissued,
andissubjecttochange.Theinformationshouldnotbeconstruedasdictatingan
exclusivecourseoftreatmentorproceduretobefollowed.Localinstitutionscan
dictateamendmentstotheseopinions.Theyshouldbewelldocumentedifmodified
atthelocallevel.Noneofthesecontentsmaybereproducedinanyformwithout
priorwrittenpermissionoftheSOGC.
ABSTRACT
Objective:Todefineaguidelineformanagingabnormalcytologyresultsafterscreeningforcervicalcancerandtoclarifytheappropriatealgorithmsforfollow-upaftertreatment.
Options:Womenwithabnormalcytologyareatriskofdevelopingcervicalcancer;appropriatetriageandtreatmentwillreducethisrisk.
Outcomes:AqualityguidelinewillfacilitateimplementationofcommonstandardsacrossCanada,movingawayfromthecurrenttrendofindividualguidelinesineachprovinceandterritory.
Evidence:PublishedliteraturewasretrievedthroughsearchesofPubMedorMEDLINE,CINAHL,andTheCochraneLibraryinOctober2008usingappropriatecontrolledvocabulary(e.g.,colposcopy,cervicaldysplasia)andkeywords(e.g.,colposcopymanagement,CIN,AGC,cervicaldysplasia,LEEP,LLETZ,HPVtesting,cervicaldysplasiatriage).Resultswererestrictedtosystematicreviews,randomizedcontroltrials/controlledclinicaltrials,andobservationalstudies.Therewerenodateorlanguagerestrictions.SearcheswereupdatedonaregularbasisandincorporatedintheguidelinetoDecember2011.Grey(unpublished)literaturewasidentifiedthroughsearchingtheWebsitesofhealthtechnologyassessment(HTA)andHTA-relatedagencies,clinicalpracticeguidelinecollections,andfromnationalandinternationalmedicalspecialtysocieties.Expertopinionfrompublishedpeer-reviewedliteratureandevidencefromclinicaltrials(whereavailable)issummarized.Consensusopinionisoutlinedwhereevidenceisinsufficient.
Values:ThequalityoftheevidenceisratedusingthecriteriadescribedbytheCanadianTaskForceonPreventiveHealthCare(Table1).Thetaskforcehasrecentlyreconvenedandnonewrecommendationshavebeenreleased.
Benefits,HarmsandCosts:Theintentistopromotethebestpossiblecareforwomenwhileensuringefficientuseofavailableresources.
Validation:Thisguidelinehasbeenreviewedforaccuracyfromcontentexpertsin
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cytology,pathologyandcervicalscreeningprograms.GuidelinecontentwasalsocomparedtosimilardocumentsfromotherorganizationsincludingtheAmericanSocietyforColposcopyandCervicalPathology,BritishSocietyforColposcopyandCervicalPathology,andtheEuropeanCancerNetwork.
Sponsors:None
KeyWords:CervicalCytology,CervicalCancer,Colposcopy,Treatment,Follow-up,Abnormalities,Guidelines
Recommendations
WaitTimesforColposcopy1. WomenwithHSILareideallyseeninacolposcopyclinicwithin4weeksof
referral.(III-C)
2. WomenwithASC-HorAGCshouldbeseeninacolposcopyclinicwithin6weeksofreferral.(III-C)
3. WomenwithaPaptestsuggestiveofcarcinomashouldbeseenwithin2weeksofreferral.(III-C)
4. Otherresultsshouldbeseeninacolposcopyclinicwithin8weeksofreferral.(III-C)
TheColposcopyExam1. Colposcopicfindingscanbedescribedaccordingtotheterminologydefined
bytheInternationalFederationforCervicalPathologyandColposcopy.(III-C)
2. Atcolposcopy,twoormorebiopsiesshouldbetaken.(I-A)
3. AnECCshouldbeperformedwhencolposcopyisunsatisfactory,withanAGCpapandinolderwomenwithhigh-gradecytology.(II-2B)
4. RoutineHR-HPVtestingforallcolposcopyreferralsisdiscouraged.(III-C)
ManagingwomenwithASCUSorLSILonreferraltoColposcopy1. Acolposcopicallyidentifiedlesionshouldbebiopsied.(III-C)
2. Ifnolesionisidentified,arandombiopsyofthetransformationzonecouldbeconsidered.(III-C)
ManagingASC-H1. AwomanwithanASC-HPaptestshouldhavecolposcopytoruleoutCIN2/3
and/orcancer.(II-2A)
2. WithanASC-HPaptest,thefindingofnegativecolposcopydoesnotautomaticallywarrantadiagnosticexcisionalprocedure.(III-B)
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ManagingHSIL1. AllwomenwithanHSILtestresultshouldhavecolposcopy.(II-2A)
2. Intheabsenceofanidentifiablelesionatcolposcopyandunsatisfactorycolposcopy,adiagnosticexcisionalprocedureshouldbeperformed.(III-B)
ManagingAtypicalGlandularCytology(AGC-NOS,AGC-N,AIS)1. ThefindingofanAGCPaptestwarrantscolposcopy.(II-2A)
2. AnAGC-NPaptestwithoutanidentifiablelesionatcolposcopyshouldbefollowedwithadiagnosticexcisionalprocedure.(II-2A)
ManagingSCCandAdenocarcinoma1. Womenwithacytologicdiagnosissuggestiveofcarcinoma,withorwithouta
visiblelesion,shouldhavecolposcopy.(IIIA)
ManagingthePatientwithAbnormalHPVTestandNormalCytology1. WomenwhotestpositiveforHR-HPVandhavenegativecytologyshould
haverepeattestingat12months.PersistentpositiveHR-HPVtestswarrantcolposcopy.(IA)
ManagingAbnormalCytologyinPregnancy1. WomenwithanASCUSorLSILtestresultduringpregnancyshouldhave
repeattestingpostpregnancy.(III-B)
2. WomenwithHSIL,ASC-HorAGCshouldbereferredpromptlyforcolposcopyinpregnancy.(III-B)
3. ECCisnotrecommendedduringpregnancy.(III-B)
ManagingAbnormalCytologyintheAdolescent1. Screeningshouldnotbeinitiatedinwomenlessthan21yearsofage.(II-2A)
2. Ifscreeningisdone,andanASC-USorLSILresultisreported,cytologyshouldberepeatedinoneyear,withreferraltocolposcopyifalow-gradetestresultcontinuesfor24months.(III-B)
3. CytologyresultsofASC-H,HSIL,andAGCintheadolescentshouldbereferredtocolposcopy.(III-B)
ManagingHistologicalAbnormalities
ManagingCIN11. BiopsyprovenCIN1shouldbeobservedwithrepeatcolposcopyat12-month
intervals.Persistencebeyond24monthsmaybetreatedorobservedwithrepeatcytologyand/orcolposcopy.(II-1B)
2. Biopsy-provenCIN1afterHSILorAGCcytology,anexcisionalprocedureshouldbeconsidered.(III-B)
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ManagingCIN2/31. CIN2or3shouldbetreated;excisionalproceduresarepreferredforCIN3.
(II-1A)
2. Womenwhohavepositivemarginsshouldhaveclosefollow-upwithretreatmentwithexcisionforpersistentdisease.(II-1B)
ManagingCIN2/3intheAdolescent1. CIN2intheadolescentpatientshouldbeobservedwithcolposcopyat6-
monthintervalsforupto24monthsbeforetreatment.(II-2B)
2. CIN3shouldbetreatedintheadolescentpatient.(III-B)
ManagingAdenocarcinomainSitu(AIS)1. IfAISisdiagnosed,treatmentneedstobedonewithadiagnosticexcisional
procedure,ortype3TZexcision.(II-2A)
2. Ifmarginsarepositiveafterdiagnosticexcisionalprocedure,asecondexcisionalprocedureshouldbeperformed.(II-2A)
3. IfaftertreatmentforAISawomanhasfinishedchildbearing,ahysterectomyshouldbeconsidered.(III-B)
4. IfAISisdiagnosedafterLEEPisperformedforCINinawomanwhohasnotcompletedherfamilyandmarginsarenegative,itisunnecessarytoperformafurtherdiagnosticexcisionalprocedure.(II-2A)
ManagingHistologicalAbnormalitiesDuringPregnancy1. IfCIN2orCIN3isdiagnosedduringpregnancy,treatmentshouldbedelayed
untilafterdelivery.(II-2A)
Follow-upPostTreatment1. Post-treatmentforCIN2or3:womenshouldbefollowedwithcytologyand
colposcopyat6monthintervalsfortwovisits,aslongasbothcytologyandanybiopsiesarenegative.(II-2B)
2. Post-treatmentforCIN2or3:HPVtestingat6or12monthscombinedwithcytology.IfbothcytologyandHPVtestingarenegative,returningtoannualorbiannualcytologyisareasonableoption.(II-2B)
ManagingHistologicalAbnormalitiesinHigh-RiskIndividuals1. Immunocompromisedwomenshouldbescreenedannuallybutnotwith
colposcopy.(II-2B)
2. Immunocompromisedwomenshouldbetreatedwithanexcisionalproceduretakingcaretominimizepositivemargins.(II-2B)
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Table1:Keytoevidencestatementsandgradingofrecommendations,usingtherankingoftheCanadianTaskForceonPreventativeHealthCare
QualityofEvidenceAssessment* Classificationof
Recommendations‡
I: Evidenceobtainedfromatleastoneproperlyrandomizedcontrolledtrial
II-1: Evidencefromwell-designedcontrolledtrialswithoutrandomization
II-2: Evidencefromwell-designedcohort(prospectiveorretrospective)orcase-controlstudies,preferablyfrommorethanonecentreorresearchgroup
II-3: Evidenceobtainedfromcomparisonsbetweentimesorplaceswithorwithouttheintervention.Dramaticresultsinuncontrolledexperiments(suchastheresultsoftreatmentwithpenicillininthe1940s)couldalsobeincludedinthecategory
III: Opinionsofrespectedauthorities,basedonclinicalexperience,descriptivestudies,orreportsofexpertcommittees
A. Thereisgoodevidencetorecommendtheclinicalpreventiveaction
B. Thereisfairevidencetorecommendtheclinicalpreventiveaction
C. Theexistingevidenceisconflictinganddoesnotallowtomakearecommendationfororagainstuseoftheclinicalpreventiveaction;however,otherfactorsmayinfluencedecision-making
D. Thereisfairevidencetorecommendagainsttheclinicalpreventiveaction
E. Thereisgoodevidencetorecommendagainsttheclinicalpreventiveaction
L. Thereisinsufficientevidence(inquantityorquality)tomakearecommendation;however,otherfactorsmayinfluencedecision-making
*ThequalityofevidencereportedintheseguidelineshasbeenadaptedfromTheEvaluationofEvidencecriteriadescribedintheCanadianTaskForceonPreventiveHealthCare.
†RecommendationsincludedintheseguidelineshavebeenadaptedfromtheClassificationofrecommendationscriteriadescribedinTheCanadianTaskForceonPreventiveHealthCare.
IntroductionOverthelast30yearscervicalcancermorbidityandmortalityrateshavedroppedsignificantlyinCanada,fromapproximately30per100,000to7per100,000
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women(1).Thischangehasbeenwidelyattributedtotheavailabilityofcervicalscreeningviacytologicsampling(2).
Colposcopyhasevolvedtoevaluatethosewithabnormalcytologyandprovideahistologicalsamplebybiopsy.Treatmentoflesionscanthenbeperformed,usuallypreservingfertilityandavoidingmajorsurgery(3)(Ch1,p6).Numerousjurisdictionshavedevelopedguidelines(4-8)forcolposcopy1andthesehavebeenreviewedindevelopingthisdocument.
CervicalcancerscreeningisorganizedwithineachprovinceandterritoryinCanada.ScreeningProgramsissuescreeningandfollow-uprecommendationsforabnormalscreeningresults,includingreferraltocolposcopy.ThediversityandstatusofcervicalscreeninginCanadahasbeensummarizedelsewhere(9).
Theageforinitialscreeninghasbeenre-evaluatedrecently.ThisreviewofscreeninginitiationwaspioneeredbytheAmericanSocietyofColposcopyandCervicalPathology(ASCCP),whichconvenedaconsensuspracticeimprovementconferenceinJune2009.StakeholdersfromtheUnitedStates(USA)andCanadawereincluded.Outcomesfromthismeetingincludedarecommendationtostartscreeningatage21(10).ThisrecommendationhasbeenincorporatedintonewguidelinesfromQuébec(11)andAlberta(12).
Canadiancolposcopicpracticeisuniqueinseveralways.Colposcopyisperformedpredominantlybygynecologistsinbothhospitalclinicsandprivateoffices.AccesstoHPVtestingiscurrentlylimitedoutsideofteachinghospitals.TheprimaryaimoftheseguidelinesistostandardizethecolposcopiccareprovidedforwomeninCanada.
MethodsTheseguidelinesweredevelopedthroughtheleadershipoftheSocietyofCanadianColposcopy.Inputwassolicitedfromvariousorganizationsincluding;SocietyofGynecologicOncologyofCanada(GOC);SocietyofObstetriciansandGynecologistsofCanada(SOGC);CanadianAssociationofPathologists(CAP);CanadianSocietyofCytopathology(CSC);and,representationfromprovincialscreeningprograms.Aface-to-facemeetingofcontributorswasheldinDecember2008forthefollowingpurpose.Relevantliteraturewasreviewed,includingguidelinesrelatedtocolposcopicmanagementofabnormalcytologyandhistology.Clinicalquestionsweredevelopedanddiscussed.Whereevidencewasincomplete,consensusopinionprevailed.Guidelinesexistbothasformallypublishedandweb-baseddocuments;themostcommonlyreferencedarethosepublishedbytheAmericanSocietyforColposcopyandCervicalPathology(ASCCP)formanagementofcytologicalandhistologicalabnormalities(13,14).
1GuidelinesfrombothwithinandoutsideCanadahavebeenreviewedandwillbereferenced,whereappropriate,throughoutthedocument.
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TheBethesda2001classificationsystem(15)isthecytologicalterminologycommonlyusedinCanada;thisterminologywasusedheretorepresentcytologicaldiagnosesandCINterminologywasemployedforhistologicaldiagnoses.(SeealsoTable2)
ColposcopicManagementofCytologicalAbnormalitiesScreeningandcolposcopyrecommendationsvaryacrossprovincesandterritoriesandhavebeendocumentedelsewhere(9).Currentguidelinesforcolposcopicreferralscanbesummarizedasfollows:referraltocolposcopyisrecommendedforpersistentASCUS,persistentorincidentLSIL,ASC-H,HSIL,andAGC2aswellasforPapanicolaou(Pap)teststhatsuggestsquamousorglandularcarcinoma.HPVtestingisnotwidelyavailable;however,whenreflexHPVtestingshowsthepresenceofoncogenic(orhighrisk)HPV(HR-HPV)withASCUScytology,referraltocolposcopyisrecommended.
WaitTimesforColposcopyPatientswithabnormalscreeningtestsshouldbeseenincolposcopywithinareasonabletime,giventheriskofhigh-gradechangesandpsychologicalstressassociatedwithanabnormalcytologyresult(16).Becauseofthis,theSOGCwaittimesstatementrecommendscolposcopicassessmentwithin3weeksforHSILcytology;6–8weeksforASC-HorLSIL;and6weeksforanAGCcytologyresult(17)TheserecommendationsaresimilartotheUKrecommendationthat90%ofcaseswithhigh-gradecytologyshouldbeseenwithin4weeksand90%ofalltestsshouldbeseenwithin8weeksofreferral(7).
TheimportanceofguidelinestodirectreferraltimestocolposcopywasillustratedinanOntariopopulation-basedreview(18).ReferralswerereviewedforPaptestresultsofHSIL,AGCandASC-Hbetween2000and2006.WomenwithHSILresultswereseenincolposcopyatamediantimeof67days,AGC108daysandASC-H80days.Invasivediseaseofthelowergenitaltractwasdetectedin2.4%ofASC-Hcases,3%ofAGCand3.12%ofHSIL.Unfortunatelyinthispopulationtherewasa26%losstofollow-up,i.e.,womenwhodidnothavecolposcopywithin24months.
Itisrecognizedthattheseareguidelinesandmaybedifficulttoachieve;however,triageeffortsshouldensurethatthosewithmoresignificantcytologicabnormalitiesareseenfirst.
Recommendations:
1. WomenwithHSILareideallyseeninacolposcopyclinicwithin4weeksofreferral.(III-C)
2. WomenwithASC-HorAGCshouldbeseeninacolposcopyclinicwithin6weeksofreferral.(III-C)
2SeeTable2fordescriptionoftheseterms.
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3. WomenwithaPaptestsuggestiveofcarcinomashouldbeseenwithin2weeksofreferral.(III-C)
4. Otherresultsshouldbeseeninacolposcopyclinicwithin8weeksofreferral.(III-C)
TheColposcopyExamColposcopyistheexaminationofthelowergenitaltractandcervixusingmagnificationfromacolposcopewithagoodlightsource.Thesquamo-columnarjunctionandtransformationzoneshouldbeidentified,determiningwhethertheexamissatisfactoryornot.Aceticacidisthenusedtoassessthesize,shape,marginandlocationofanyneoplasticlesion.ThesefindingscanthenbedescribedaccordingtothenomenclatureoftheInternationalFederationforCervicalPathologyandColposcopy(19).
Whenanylesionisidentified,recentevidencesupportsthepracticeoftakingatleasttwobiopsiestoimprovetheaccuracyofcolposcopy.Abiopsyshouldbetakenofthemostsevereareafoundoncolposcopicexamination,eithertoconfirmorruleoutmalignantlesions(20,21).AnalysisoftheALTSdatashowedthat,takingtwobiopsiesforalow-gradecytologyreferralatinitialcolposcopy,improvedthesensitivity(todetectCIN2orgreater)to81.8%,comparedto68.3%withonebiopsy(20).
ArecentreviewoftheutilityofendocervicalcurettagewaspublishedusingdatafromCalgary.Basedonover13,000examinations,theauthorsshowedthat99ECCspecimenshadtobetakentodetectoneadditionalcaseofCIN2orhighergradelesion.Thelargestbenefitwasinolderwomenreferredafterhigh-gradecytology(22).AnECCshouldthusbeperformedwithunsatisfactorycolposcopy,anAGCsmear,andinolderwomenwithhigh-gradecytology
Alowthresholdisrecommendedforundertakingabiopsy.Ifanylesionisseen,biopsyshouldbecompleted.Ifonlymetaplasiaisinquestion,abiopsyshouldbeconsidered.Unlessdictatedbytheappropriatealgorithm,thereisnoroleforroutineHR-HPVtestinginthecolposcopyclinic.
Recommendations:
1. ColposcopicfindingscanbedescribedaccordingtotheterminologydefinedbytheInternationalFederationforCervicalPathologyandColposcopy.(III-C)
2. Atcolposcopy,twoormorebiopsiesshouldbetaken.(I-A)
3. AnECCshouldbeperformedwhencolposcopyisunsatisfactory,withanAGCpapandinolderwomenwithhigh-gradecytology.(II-2B)
4. RoutineHR-HPVtestingforallcolposcopyreferralsisdiscouraged.(III-C)
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ManagingwomenwithASCUSorLSILonreferraltoColposcopyManagementoflow-gradeabnormalitiesremainscontroversial.AlargerandomizedtrialintheUSAconcludedthatwomenwithLSILcytologyresultswerebestmanagedbyimmediatereferraltocolposcopy;itwasnotedthat83%werepositiveforHR-HPVandthusHPVtriagewouldnotbeeffective(23).ThesamestudyreportedthatwomenwithASCUSresults,butnegativeforHR-HPV,couldsafelybetriagedawayfromcolposcopy(23).ThisapproachrequiresavailabilityofreflexHPVtesting;unfortunately,thisisnotwidelyavailableinCanada.ArecentmulticenterstudyintheUKevaluatedthemanagementofsimilarlowgradecytology.Outcomesindicatedthatapolicyofimmediatecolposcopyledtoincreasedreferralstocolposcopywithnoclearbenefitandpotentialharm(24).
Withlow-gradelesions,colposcopyisdonetoruleoutpotentiallypre-malignantchangesi.e.,CIN2or3;ifthisisdetected,managementisundertakenaccordingtotheappropriateprotocol.Ameta-analysisreportedCIN2+ratesof10%andCIN3+of6%withanASCUSreferral(25,26).WithanLSILreferral,theratesofCIN2+are17%andCIN3+12%(27,28).IfCIN1isthehighestgradeidentifiedatcolposcopy,conservativemanagementisrecommended.Ifnolesionisidentifiedatcolposcopy,arandombiopsyatthetransformationzoneshouldbeconsidered.Asperconsensusopinion,ifnodysplasiaisidentifiedatcolposcopy,annualscreeningwiththereferringhealthcareproviderisrecommended,untilthreenegativePaptestshavebeenreported.Ifallcytologyisnegative,womenmaythenbefollowedevery2to3years,consistentwithprovincial/territorialguidelines.
Recommendations:
1. Acolposcopicallyidentifiedlesionshouldbebiopsied.(III-C)
2. Ifnolesionisidentified,arandombiopsyofthetransformationzonecouldbeconsidered.(III-C)
ManagingASC-HWithanASC-HresultonthePaptest,significantpathologyistypicallyfoundinthemajorityofcases.Inastudyof517casesfromEdmonton,Alberta,CIN2orgreaterwasdetectedin70%ofcases(29).MostcaseswereCIN2;however,invasivecarcinomawasreportedin2.9%ofcasesandAISin1.7%(29).AsimilarOntariostudyshowedCIN2orgreaterin59.4%ofcaseswithastrongercorrelationinwomenyoungerthan40years(30).AllwomenwithASC-Hshouldhavecolposcopytoruleoutsignificantpathology.Ifcolposcopyisnegative,recommendationsincludecolposcopy,repeatcytologyand,ideally,HR-HPVtestingtwice,atsixmonthintervals,toavoidmissingasignificantlesion.Iftheserepeattestsarenegative,womenmayreturntoregularscreening,asperprovincial/territorialprotocol.ThefindingofASC-Hwithnegativecolposcopydoesnotwarrantaconebiopsyordiagnosticexcisionalprocedurefordiagnosticpurposes.
Recommendations:
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1. AwomanwithanASC-HPaptestshouldhavecolposcopytoruleoutCIN2/3and/orcancer.(II-2A)
2. WithanASC-HPaptest,thefindingofnegativecolposcopydoesnotautomaticallywarrantadiagnosticexcisionalprocedure.(III-B)
ManagingHSILTheriskofasignificantlesionishighwithHSILcytology.StudieshaveshownCIN2orgreaterin53-66%ofcaseswhencolposcopicbiopsiesaretaken,andupto90%ifanimmediateLEEPisperformed(31,32).Becauseofthishighrateofsignificanthigh-gradehistology,allwomenwithanHSILresultshouldhavecolposcopy.AvisualassessmentandLEEPapproachmaybeappropriateinsomecircumstances,butacolposcopicallydirectedbiopsyandtailoredtreatmentispreferred.
Ifalesionisnotdetectedatcolposcopy,andcolposcopyisnotsatisfactory,thenadiagnosticexcisionalprocedureshouldbedone.Thiscanbeachievedwithaconebiopsy,orLEEPusingalargeloop,orasecondendocervicalpass.However,ifnolesionwasdetected,andcolposcopywassatisfactory,combinedcolposcopyandcytologyisappropriateatsix-monthintervalsfortwovisits.Thissituationisrare.Amongwomenwhohavefinishedchildbearing,adiagnosticexcisionalprocedureshouldbeconsidered.
Recommendations:
1. AllwomenwithanHSILtestresultshouldhavecolposcopy.(II-2A)
2. Intheabsenceofanidentifiablelesionatcolposcopyandunsatisfactorycolposcopy,adiagnosticexcisionalprocedureshouldbeperformed.(III-B)
ManagingAtypicalGlandularCytology(AGC-NOS,AGC-N,AIS)ThefindingofAGC-NOS,AGC-NorAISalwayswarrantspromptreferraltocolposcopyintheabsenceofothersymptomatology.Neoplasticlesionsotherthanfromthecervix,includingendometrium,ovaryandfallopiantube,havebeenidentifiedwithAGCcytology(33-35).InaCanadianreport456casesofAGCorAGUSwereidentifiedoutofadatabaseofover1millionPaptests(0.043%)(34).Onfinalhistology7%werefoundtohaveCIN1,36%CIN2or3,AISwasidentifiedin20%,carcinomaofthecervixin9%,andendometrialpathologyin29%,includingcarcinomaoftheendometriumin10%.ItshouldbenotedthatCINisconsistentlythemostfrequentfindingacrossmanystudies(33,34,36,37).ThishighrateofpathologyprecludesanyattempttotriageusingrepeatcytologyorHPVtesting.
ThediagnosisofAGC-Nisassociatedwithhigherratesofabnormalitiesandthus,intheabsenceofanabnormalityfoundbycolposcopy,adiagnosticexcisionalprocedureshouldbeperformed(38,39).Adiagnosticexcisionalprocedureincludesacoldknifeconebiopsy,laserconebiopsyandmayincludeaLEEPifthespecimenisofsufficientsize.Ahysterectomyisnotconsideredasadiagnosticexcisionalprocedure.Endocervicalcurettage(ECC)shouldbedoneinallwomen,andendometrialsamplingshouldbeperformedinwomenover35yearsorifthereisahistoryofabnormalbleeding,includinganovulation.
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However,withAGC-NOScytologyandtheabsenceofanidentifiedlesion,womenarestillatriskofdevelopingalesion.Inthissituation,follow-upassessmenteverysixmonthsfortwoyearsincludesrepeatcytology,colposcopyandECC.IfHR-HPVtestingisavailableandwasdoneattheinitialcolposcopyvisit,womenwhotestnegativeforHR-HPVmayhaverepeatassessmentwithcolposcopy,cytology,ECCandHR-HPVtestingat12months.Ifalesionisidentified,treatmentisguidedbythespecificguideline.Ifacarcinomaisidentified,referralshouldbemadetoagynecologiconcologist.Ifallfollowupisnegativeaftertwoyears,routinecytologictestingmayberesumed.
Recommendations:
1. ThefindingofanAGCPaptestwarrantscolposcopy.(II-2A)
2. AnAGC-NPaptestwithoutanidentifiablelesionatcolposcopyshouldbefollowedwithadiagnosticexcisionalprocedure.(II-2A)
ManagingSCCandAdenocarcinomaWomenshouldbereferredpromptlytocolposcopyiftheirPaptestissuggestiveofcarcinoma,withorwithoutavisiblelesion.AssessmentshouldincludecolposcopyanddirectedbiopsywithconsiderationofECC.Ifnoabnormalityisdetected,adiagnosticexcisionalprocedureisrecommendedtoruleoutoccultcarcinoma.EndometrialbiopsyshouldalsobecontemplatedintheworkupofwomenwithadenocarcinomaonaPaptest.
Recommendation:
1. Womenwithacytologicdiagnosissuggestiveofcarcinoma,withorwithoutavisiblelesion,shouldhavecolposcopy.(IIIA)
ManagingthePatientwithAbnormalHPVTestandNormalCytologyForthosewomenwithASCUSandpositivereflexHR-HPV,womenshouldbereferredtocolposcopy.However,noprovincialguidelinesaddressmanagementofnegativecytologyfindingscombinedwithapositiveHR-HPVresult.
WomenwithnegativecytologyandpositiveHPVresultsshouldhaverepeatsofbothtestsaftertwelvemonths(40,41),withtheirprimaryhealthcareprovider.Ifbothtestsarenegativeat12months,womenshouldreturntoscreeningasperprovincial/territorialguidelines.Womenwithacytologicalabnormalityshouldbemanagedaccordingtothecytologicaldiagnosis.IfthereispersistentHR-HPVontwotestsoneyearapart,referraltocolposcopyisrecommendedtoruleoutthepossibilityofahigh-gradelesion.
Recommendation:
1. WomenwhotestpositiveforHR-HPVandhavenegativecytologyshouldhaverepeattestingat12months.PersistentpositiveHR-HPVtestswarrantcolposcopy.(I-A)
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ManagingAbnormalCytologyinPregnancyTheindicationsforcolposcopyduringpregnancyareessentiallythesameasfornon-pregnantwomen.Ifalow-gradelesion(ASCUSorLSIL)isfoundduringpregnancy,thePaptestshouldberepeatedatleastsixweekspostpartum.Thispracticeissafeastherateofcancerinthisgroupisverylow(42).IfHSIL,ASC-HorAGCisfound,promptevaluationwithcolposcopyisessential.Ifcolposcopyisunsatisfactoryinthefirsttrimester,itshouldberepeatedafter20weeksgestationwhen,becauseofthephysiologicalchanges,thecervixevertsitselfandthesquamo-columnarjunctionmaybecomevisible.
IfCIN3orcarcinomaissuspected,biopsyisrecommended.Thereisevidencethatbiopsyinpregnancyisnotharmful(43).Womenwithhigh-gradedysplasiainpregnancyshouldbeseenbyanexperiencedcolposcopist.
Recommendations:
1. WomenwithanASCUSorLSILtestresultduringpregnancyshouldhaverepeattestingpostpregnancy.(III-B)
2. WomenwithHSIL,ASC-HorAGCshouldbereferredpromptlyforcolposcopyinpregnancy.(III-B)
3. ECCisnotrecommendedduringpregnancy.(III-B)
ManagingAbnormalCytologyintheAdolescentThereislittleevidencethatscreeningbycytologyinadolescents(lessthan21yearsold)isbeneficial.Theincidenceofcervicalcancerisverylow.SEERdatafromtheUSAshowedarateof0.1/100,000inwomen15-19yearsoldand1.6/100,000inwomen20-24yearsold,comparedto15.5/100,000inwomen40-45yearsold(44).AlthoughHPVinfectionandlow-gradePaptestsarecommoninthisagegroup,mostoftheseinfections,andrelatedcytologicalchanges,willresolvewithoutintervention(45,46).Screeningisinvasiveandcanhaveadversepsychologicalsequelaeespeciallyifitleadstocolposcopyreferral(10,47).
Ifthisscreeningleadstotreatment,treatmentbyLEEPcanlaterbeassociatedwithaslightlyincreasedriskofprematureruptureofmembranesandpretermdelivery(48,49).HPVvaccinationhasrecentlybeeninstitutedinCanadaandthehighefficacyagainstHPV16and18shouldlikelyresultinfewerhighgradelesionsneedingtreatment(50-54).ThiscollectiveevidencehasledtheAmericanCollegeofObstetricsandGynecology,aswellastheprovincesofAlbertaandQuébectorecommendanolderageforscreeninginitiation–until21yearsofage(11,12,55,56).
Amongwomenyoungerthan21years,ifaPaptesthasbeendoneandabnormalitiesaredetectedatscreening,managementshouldbeconservativetoavoidharm.Low-gradechanges,i.e.,ASC-USandLSILregressinupto93%ofcaseswithconservativemanagement.Thuswomenlessthan21yearswithASC-USandLSILresultsshouldhaverepeatcytologyinoneyearwithreferraltocolposcopyonlyifabnormalities
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persistfor24months(10).Womenyoungerthan21years,withASC-H,HSIL,orAGCresults,shouldbereferredtocolposcopy.
Recommendations:
1. Screeningshouldnotbeinitiatedinwomenlessthan21yearsofage.(II-2A)
2. Ifscreeningisdone,andanASC-USorLSILresultisreported,cytologyshouldberepeatedinoneyear,withreferraltocolposcopyifalow-gradetestresultcontinuesfor24months.(III-B)
3. CytologyresultsofASC-H,HSIL,andAGCintheadolescentshouldbereferredtocolposcopy.(III-B)
ManagingHistologicalAbnormalitiesOncealesionhasbeenidentifiedoncolposcopy,andbiopsycompleted,adecisionmustbemaderegardingmanagement.Theaimoftreatmentistoremoveapotentiallyprecancerouslesiontoavoiddevelopmentofcarcinoma.TheinitialclassificationofcervicalintraepithelialneoplasiaasCIN1,2or3wasproposedbyRichartin1973andsubsequentlyreinforcedbytheWorldHealthOrganizationin1994(57).TherateofprogressionofthesedysplasticlesionshasbeenwellreviewedbyOstor(58)(Table3),andovertimethetherapeuticapproachhasbeenadaptedtoavoidharmwhenlesserCINgradesareunlikelytoprogresstoinvasivecancer.
Treatmentmodalitiesincludeeitherexcisionalorablativeapproaches(cryotherapyorlaserablation).ThefavouredmethodinCanadaisexcisional-theloopelectrosurgicalexcisionprocedure(LEEP).Althoughrelativelyeasytoperformintheoutpatientsetting,therecanbecomplications.Arecentmeta-analysisestimatedthat,afteraLEEPprocedure,theriskforpretermdeliveryinasubsequentpregnancyoflessthan32-34weeksgestation,was1in143treatments(48).Thesameresearchgroupsuggestedthatadepththresholdof10mmisalsoavariableinreducingharm.Consequently,ifthecolposcopistisabletoadjusttheproceduretothelesion,futurenegativesequelaeinpregnancymaybeminimized(59).
Treatmentistailoredtothelesionidentifiedonthecervix,byeitherremovingorablatingtheentiretransformationzone.TheInternationalFederationofCervicalPathologyandColposcopy(IFCPC)hasclassifiedthetransformationzone(TZ)intothreecategories(60).Atype1TZiscompletelyectocervical,andfullyvisible.Atype2TZisfullyvisible,hasanendocervicalcomponentandmayhaveanectocervicalcomponent.Atype3TZispredominantlyendocervical,notfullyvisibleandmayhaveanectocervicalcomponent(Figure1).
Usingthisclassification,ablativemethodscanbeusedforatype1or2TZifrecognizedcriteriaaremet(Table4).IfexcisionwithLEEPisutilizedthesizeofloopelectrodemustbeadjusteddependingonthelesion,i.e.,atype2TZrequiresalargerloopelectrodethanatype1TZtoensurethelesionisfullyexcised.Ifthelesionisnotseeninitsentirety,colposcopyisunsatisfactoryandablativetherapiesshouldnotbeused(60,61).Careshouldbetakentoavoidremovalofexcessive
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cervicalstromawhichwouldpredisposewomentopretermdelivery,especiallyifusingverylargeloopsortakingmultiplepasses.
Atype3TZwithalesionthatextendsintotheendocervicalcanal,oraglandularlesion,requiresalargerorlongerexcisionforadequateevaluationortreatment.ThisdocumentadoptedthenewIFCPCterminologytoidentifythisprocedureasatype3excisiontoavoidthecurrentconfusioninterminology(62).Currently,conebiopsy,diagnosticexcisionalprocedure,laserexcisionandLEEPmaybeusedbuthavedifferentmeaningstoindividualcolposcopists(61).
ManagingCIN1EvidencefromtherecentALTStrialhasconfirmedsignificantinter-observervariabilityinthehistologicaldiagnosisofCIN1,withtheoverlapoftenobservedwithbenignHPVinfection(63).OurcurrentunderstandingisthatCIN1seldomprogressestoinvasivediseaseandthatitwillregresswithouttreatmentwithin2-5yearsin60-80%ofallcases(58,64).Regressionratesareevenmorepronouncedinadolescents,withregressionoflow-gradesquamousintra-epitheliallesionsinupto91%ofcasesoverathree-yearperiod(65).ThisknowledgehasledtoachangeinthetreatmentphilosophyforCIN1.
ConservativemanagementwithobservationispreferredforCIN1.Womenshouldbefollowedwithrepeatcytologyandcolposcopyat12-monthintervals;ifnolesionisidentifiedshemayreturntoroutinescreening.Ifthelesionpersistsfor24monthsorlonger,treatmentisacceptable.Ifcolposcopyissatisfactory,treatmentmaybebyablativemodalities.Howeverinacompliantpatient,longerfollow-upispossible,especiallyinwomenwhohavenotcompletedchildbearing.
TheexceptiontoaconservativeapproachoccurswhenadiagnosisofCIN1isprecededbyHSILorAGCcytology.Inthesesituations,histologicalfindingshavenotadequatelyexplainedtheabnormalcytologyandanexcisionalprocedureshouldbeconsidered.
Recommendations:
1. BiopsyprovenCIN1shouldbeobservedwithrepeatcolposcopyat12-monthintervals.Persistencebeyond24monthsmaybetreatedorobservedwithrepeatcytologyand/orcolposcopy.(II-1B)
2. Biopsy-provenCIN1afterHSILorAGCcytology,anexcisionalprocedureshouldbeconsidered.(III-B)
ManagingCIN2/3PathologicallyconfirmedhighgradedysplasiaincludesCIN2andCIN3,thesearetreatedinthesamefashioninmostjurisdictions(7,13,66-69).Therearehoweverdifferencesintheratesofregression.TheclassicalreviewbyOstorshowedthatCIN2regressesin43%andprogressedtoCIN3+in27%thiscomparestoregressionof33%persistenceof52%andprogressiontoinvasioninatleast12%ofCIN3cases(58).(SeeTable3.)ThetruemalignantpotentialofCIN3hasbeendemonstratedinNewZealandbylong-termfollow-upofCIN3thatwasnottreated.Thisshowedthat
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theinvasiveriskinuntreatedCIN3is31%over30years,alsonotingthatpatientswithdocumentedpersistentCIN3for2yearshadariskofsubsequentinvasionof50%(70).
ForthesereasonsmostwomenwithCIN2or3shouldbetreated3.Ifcolposcopyissatisfactory,i.e.,atype1or2TZ,excisionandablativetherapyarebothacceptable;however,anexcisionalprocedureispreferredforthetreatmentofCIN3.IfCIN2or3isidentifiedandcolposcopyisunsatisfactory,anexcisionalprocedureshouldbeperformed.Ifattreatment,marginsarepositiveforCIN,ortheECC(ifdone)ispositive,thesewomenareatincreasedriskofpersistentdysplasia.Inameta-analysisofexcisionaltreatment,theriskofpost-treatmentdiseasewas18%forincompleteexcisionand3%forcompleteexcision(71).Ifthedeepmarginsareinvolved,considerationshouldbemadeforrepeatexcision.Mostwomenshouldbefollowedwithrepeatcolposcopyat6months(72).HysterectomyisnotrecommendedasinitialtherapyforCIN2or3butmaybeperformedforwomenwithpersistentCIN.
Recommendations:
1. CIN2or3shouldbetreated;excisionalproceduresarepreferredforCIN3.(II-1A)
2. Womenwhohavepositivemarginsshouldhaveclosefollow-upwithretreatmentwithexcisionforpersistentdisease.(BII-1B)
ManagingCIN2/3intheAdolescentAsdiscussedearlierthereislittleevidencetojustifyroutinescreeningintheadolescentpatient.Ifhowever,Papscreeningiscompleted,thesepatientsmaybereferredforcolposcopy.Managementmustbemodifiedtoavoidharm.RecentevidencesuggeststhatregressionofCIN2inthispopulationoccursataratesimilartoCIN1(10,46,73,74).
Basedontheevidence,thisgroup’sconsensusopinionisthatCIN2intheadolescentcanbeobservedwithrepeatcolposcopyandcytologyevery6monthsforupto24months.Ifdysplasiapersiststhepatientshouldbetreated,eitherwithablativemethodsoraLEEP.Thisisconditionalonasatisfactorycolposcopy;ifitisunsatisfactory,treatmentshouldbeperformedwithanexcisionalprocedure.ArecentstudylookedatregressionratesofCIN2inwomenlessthan25yearsold,mostwere20-25yearsold,theoverallregressionrateoveramedianof8monthswas62%.Thissuggeststhatobservationmaybereasonableinyoungwomenlessthan25yearsold(20).Insomecenters,high-gradehistologyisdesignatedasHSIL,i.e.,CINterminologyisnotused.IfthebiopsyisreportedasHSILinanadolescentwomanwesuggestareviewofthehistologyusingCINterminology.IfreclassifiedasCIN3,treatmentbyanexcisionalmethodispreferred.
3Remainingwomen–thosewhoareyoungerorpregnant–aremanagedasoutlinedelsewhereinthisdocument.
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Recommendations:
1. CIN2intheadolescentpatientshouldbeobservedwithcolposcopyat6-monthintervalsforupto24monthsbeforetreatment.(II-2B)
2. CIN3shouldbetreatedintheadolescentpatient.(III-B)
ManagingAdenocarcinomainSitu(AIS)InCanadatheratioofadenocarcinomatosquamouscarcinomaofthecervixisincreasing;adenocarcinomacomprises20-25%ofallcervicalcancer(75).ThisislargelyafunctionofasignificantdecreaseinsquamouscellcancersduetowidespreadavailabilityofscreeningbyPaptestsoverseveraldecades.Nevertheless,implementationofcytologyqualityassuranceinitiativesinrecentyearshasbeenassociatedwithadecreaseinadenocarcinomaofthecervix.
Incontrast,diagnosisofpremalignantadenocarcinomainsitu(AIS)occursataratioof1:50,whencomparedwithseveresquamousdysplasia(76).ConsequentlyacolposcopistwillnotoftenseeAISandthetreatmentremainscontroversial.Colposcopicfeaturescanbedifficulttoidentifyandlesionsoftenextendhighinthecanal(77).Bertrandandcolleaguesshowedthatin78%ofcasesthehighestlesioninthecanalwaslessthan20mmfromtheexocervixandnonewerehigherthan29.9mm(78).Subsequenttoadiagnosisofadenocarcinomainsitueitheronpunchbiopsyorendocervicalcurretage,adiagnosticexcisionalprocedure,ortype3TZexcisionshouldbeperformed.Marginstatusisanimportantpredictorofresidualdisease,andthusthemethodchosenfortreatmentmustpreservetheabilitytoassesstheendocervicalmargin.Arecentmeta-analysisof33studiesshowedthattheriskofresidualdiseasewas2.6%withnegativemarginsand19.4%withpositivemargins.Invasivecarcinomawasalsomorefrequentlyassociatedwithpositivemargins(5.2%)comparedwithnegativemargins(0.1%)(79).Thus,ifmarginsarepositive,asecondexcisionisrequired.
IfAISisdiagnosedaftercompletingaLEEPprocedure(becauseofaCINfinding),themarginsneedtobecarefullyexamined.IftheAISissmallandmarginsareclear,thereisnoneedtoperformanexcisionalprocedureunlesschildbearingiscomplete,whenhysterectomyshouldbeconsidered(80).
Iffertilityisnotanissueoronecannotachievenegativemargins,ahysterectomyisrecommended(79).
AftertreatmentforAIS,ifthewomanwishestopreserveherfertility,shecanbecloselyobservedinthecolposcopyclinic.Sheshouldbeseenforcolposcopy,ECCandcytologyevery6to12months,foratleast5years.HR-HPVtestingcanbeutilizedtoaidreassurance.Thereafterthepatientshouldhaveannualcytology.
Recommendations:
1. IfAISisdiagnosed,treatmentneedstobedonewithadiagnosticexcisionalprocedure,ortype3TZexcision.(II-2A)
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2. Ifmarginsarepositiveafterdiagnosticexcisionalprocedure,asecondexcisionalprocedureshouldbeperformed.(II-2A)
3. IfaftertreatmentforAISawomanhasfinishedchildbearing,ahysterectomyshouldbeconsidered.(III-B)
4. IfAISisdiagnosedafterLEEPisperformedforCINinawomanwhohasnotcompletedherfamilyandmarginsarenegative,itisunnecessarytoperformafurtherdiagnosticexcisionalprocedure.(II-2A)
ManagingHistologicalAbnormalitiesDuringPregnancyTheaimofcolposcopyinpregnancyistoruleoutadiagnosisofinvasiveormicro-invasivecarcinoma.Ifdiagnosed,thesecasesshouldbepromptlyreferredtoagynecologiconcologist.IfCIN2orCIN3isdiagnosedduringpregnancy,theavailableevidencewouldsuggestthattreatmentcanbedelayeduntilafterdelivery.TheriskofprogressionisnotaffectedbythepregnancyandregressiontoCIN1ornormalpostpregnancyisbetween31and47%(81,82).
Recommendations:
1. IfCIN2orCIN3isdiagnosedduringpregnancy,treatmentshouldbedelayeduntilafterdelivery.(II-2A)
Follow-upPostTreatmentOncetreatedforCINorAIS,awomanremainsatriskofpersistenceorrecurrenceandatlong-termriskofinvasivecarcinoma(13,83,84).FailureratesfollowingtreatmentforCINdonotvarysignificantlywiththetreatmentmethodusedandinpublishedseriesarebetween5%and13%(85,86).Theaimoffollow-upistodetectpersistentorrecurrentdysplasia.
ConventionallyinCanada,womenarefollowedaftertreatmentwithcolposcopyandcytologyat6monthintervalsfor1to2years,priortoreturningtocytologyonanannualbasiswiththeirprimaryhealthcareprovider.InrecentyearstheavailabilityofHR-HPVtestinghasraisedthepossibilityofitsusetofollowwomenandpotentiallydetectrecurrenceorpersistenceearlier.Reviewsandmeta-analyseshaveevaluatedthisapproachanddemonstratethatHPVtestingmaybemoresensitivefordetectingrecurrence(87-91).Ithasbeennotedthatanadequatelypoweredprospectivetrialisneededtotrulyevaluatethisissue(91,92).SuchatrialisunderwayinseveralCanadiancenters(93).
Recommendations:
1. Post-treatmentforCIN2or3:womenshouldbefollowedwithcytologyandcolposcopyat6monthintervalsfortwovisits,aslongasbothcytologyandanybiopsiesarenegative.(II-2B)
2. Post-treatmentforCIN2or3:HPVtestingat6or12monthscombinedwithcytology.IfbothcytologyandHPVtestingarenegative,returningtoannualorbiannualcytologyisareasonableoption.(II-2B)
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ManagingHistologicalAbnormalitiesinHigh-RiskIndividualsNumerousmedicalconditionsreportedlyaffecttheabilitytolimitprogressionofHPVinfectiontodysplasia,andhenceareassociatedwithdysplasia.Theseincludetransplantationwithassociatedimmunosuppression,medicationforconditionssuchasCrohn'sDisease,rheumatoidarthritis,diabetesorHIVinfection.MostavailableinformationrelatestotransplantandHIVpatients.Inareviewfrom1995,144womenwerefollowedafterrenaltransplant.Therewasa17.5%incidenceofdysplasia(94).Similaroutcomeswerereportedafterlivertransplantaswellas13%incidenceofHSIL(95).ThelinkbetweencervicalcancerandHIViswelldocumented.Therateofcervicalcancerisupto4-6timeshigherinHIV-positivewomen(96).Inrecentyearsimprovedsurvivalhasbeenattributedtotheavailabilityofhighlyactiveantiretroviraltherapy(HAART)(96).Inareviewof400womenwhowereHIV-positiveinCapeTown,high-riskHPVwaspresentin68%ofthesewomenand55%hadabnormalPapsmears.MostPaptestresultswerelow-gradechanges,ofwhichonly4%progressed,13%wereHSIL(97).InonereviewfromNorthAmericatheratesofCIN2+withanASCUS/LSILreferralwere13.3%inHIV-negativewomenand15.3inHIV-positivewomen(98).ThereisnogoodevidencetorecommendroutinecolposcopyinthisgroupandtheycanbescreenedwithannualPaptests(99).IfatcolposcopyCIN1isdiagnosedthesewomencanbeobservedandtreatedforpersistentdisease.CIN2/3needtobetreatedandexcisionalmethodsarepreferred.Thereisahighrateofrecurrencethusawideexcisionshouldbeused(100).HAARTtherapyseemstodecreaserecurrence.Recommendations:
1. Immunocompromisedwomenshouldbescreenedannuallybutnotwithcolposcopy.(II-2B)
2. Immunocompromisedwomenshouldbetreatedwithanexcisionalproceduretakingcaretominimizepositivemargins.(II-2B)
Recommendations
WaitTimesforColposcopy5. WomenwithHSILareideallyseeninacolposcopyclinicwithin4weeksof
referral.(III-C)
6. WomenwithASC-HorAGCshouldbeseeninacolposcopyclinicwithin6weeksofreferral.(III-C)
7. WomenwithaPaptestsuggestiveofcarcinomashouldbeseenwithin2weeksofreferral.(III-C)
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8. Otherresultsshouldbeseeninacolposcopyclinicwithin8weeksofreferral.(III-C)
TheColposcopyExam5. Colposcopicfindingscanbedescribedaccordingtotheterminologydefined
bytheInternationalFederationforCervicalPathologyandColposcopy.(III-C)
6. Atcolposcopy,twoormorebiopsiesshouldbetaken.(I-A)
7. AnECCshouldbeperformedwhencolposcopyisunsatisfactory,withanAGCpapandinolderwomenwithhigh-gradecytology.(II-2B)
8. RoutineHR-HPVtestingforallcolposcopyreferralsisdiscouraged.(III-C)
ManagingwomenwithASCUSorLSILonreferraltoColposcopy3. Acolposcopicallyidentifiedlesionshouldbebiopsied.(III-C)
4. Ifnolesionisidentified,arandombiopsyofthetransformationzonecouldbeconsidered.(III-C)
ManagingASC-H3. AwomanwithanASC-HPaptestshouldhavecolposcopytoruleoutCIN2/3
and/orcancer.(II-2A)
4. WithanASC-HPaptest,thefindingofnegativecolposcopydoesnotautomaticallywarrantadiagnosticexcisionalprocedure.(III-B)
ManagingHSIL3. AllwomenwithanHSILtestresultshouldhavecolposcopy.(II-2A)
4. Intheabsenceofanidentifiablelesionatcolposcopyandunsatisfactorycolposcopy,adiagnosticexcisionalprocedureshouldbeperformed.(III-B)
ManagingAtypicalGlandularCytology(AGC-NOS,AGC-N,AIS)3. ThefindingofanAGCPaptestwarrantscolposcopy.(II-2A)
4. AnAGC-NPaptestwithoutanidentifiablelesionatcolposcopyshouldbefollowedwithadiagnosticexcisionalprocedure.(II-2A)
ManagingSCCandAdenocarcinoma2. Womenwithacytologicdiagnosissuggestiveofcarcinoma,withorwithouta
visiblelesion,shouldhavecolposcopy.(IIIA)
ManagingthePatientwithAbnormalHPVTestandNormalCytology2. WomenwhotestpositiveforHR-HPVandhavenegativecytologyshould
haverepeattestingat12months.PersistentpositiveHR-HPVtestswarrantcolposcopy.(IA)
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ManagingAbnormalCytologyinPregnancy4. WomenwithanASCUSorLSILtestresultduringpregnancyshouldhave
repeattestingpostpregnancy.(III-B)
5. WomenwithHSIL,ASC-HorAGCshouldbereferredpromptlyforcolposcopyinpregnancy.(III-B)
6. ECCisnotrecommendedduringpregnancy.(III-B)
ManagingAbnormalCytologyintheAdolescent4. Screeningshouldnotbeinitiatedinwomenlessthan21yearsofage.(II-2A)
5. Ifscreeningisdone,andanASC-USorLSILresultisreported,cytologyshouldberepeatedinoneyear,withreferraltocolposcopyifalow-gradetestresultcontinuesfor24months.(III-B)
6. CytologyresultsofASC-H,HSIL,andAGCintheadolescentshouldbereferredtocolposcopy.(III-B)
ManagingHistologicalAbnormalities
ManagingCIN13. BiopsyprovenCIN1shouldbeobservedwithrepeatcolposcopyat12-month
intervals.Persistencebeyond24monthsmaybetreatedorobservedwithrepeatcytologyand/orcolposcopy.(II-1B)
4. Biopsy-provenCIN1afterHSILorAGCcytology,anexcisionalprocedureshouldbeconsidered.(III-B)
ManagingCIN2/33. CIN2or3shouldbetreated;excisionalproceduresarepreferredforCIN3.
(II-1A)
4. Womenwhohavepositivemarginsshouldhaveclosefollow-upwithretreatmentwithexcisionforpersistentdisease.(II-1B)
ManagingCIN2/3intheAdolescent3. CIN2intheadolescentpatientshouldbeobservedwithcolposcopyat6-
monthintervalsforupto24monthsbeforetreatment.(II-2B)
4. CIN3shouldbetreatedintheadolescentpatient.(III-B)
ManagingAdenocarcinomainSitu(AIS)5. IfAISisdiagnosed,treatmentneedstobedonewithadiagnosticexcisional
procedure,ortype3TZexcision.(II-2A)
6. Ifmarginsarepositiveafterdiagnosticexcisionalprocedure,asecondexcisionalprocedureshouldbeperformed.(II-2A)
7. IfaftertreatmentforAISawomanhasfinishedchildbearing,ahysterectomyshouldbeconsidered.(III-B)
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8. IfAISisdiagnosedafterLEEPisperformedforCINinawomanwhohasnotcompletedherfamilyandmarginsarenegative,itisunnecessarytoperformafurtherdiagnosticexcisionalprocedure.(II-2A)
ManagingHistologicalAbnormalitiesDuringPregnancy2. IfCIN2orCIN3isdiagnosedduringpregnancy,treatmentshouldbedelayed
untilafterdelivery.(II-2A)
Follow-upPostTreatment3. Post-treatmentforCIN2or3:womenshouldbefollowedwithcytologyand
colposcopyat6monthintervalsfortwovisits,aslongasbothcytologyandanybiopsiesarenegative.(II-2B)
4. Post-treatmentforCIN2or3:HPVtestingat6or12monthscombinedwithcytology.IfbothcytologyandHPVtestingarenegative,returningtoannualorbiannualcytologyisareasonableoption.(II-2B)
ManagingHistologicalAbnormalitiesinHigh-RiskIndividuals3. Immunocompromisedwomenshouldbescreenedannuallybutnotwith
colposcopy.(II-2B)
4. Immunocompromisedwomenshouldbetreatedwithanexcisionalproceduretakingcaretominimizepositivemargins.(II-2B)
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Table2:The2001BethesdaSystemTerminologyforCytology(permissionrequested)
AdaptedfromSolomonDetal.(15)
SquamousCell
¨ Atypicalsquamouscells
o Ofundeterminedsignificance
o Cannotexcludehigh-gradesquamousintraepitheliallesions
¨ Low-gradesquamousintraepitheliallesions-encompassinghumanpapillomavirus,milddysplasiaandCIN1
¨ High-gradesquamousintraepitheliallesions-encompassingmoderateandseveredysplasia,carcinomainsitu,CIN2andCIN3
¨ Squamouscellcarcinoma
GlandularCell
¨ Atypicalglandularcells(specifyendocervical,endometrial,ornototherwisespecified)
¨ Atypicalglandularcells,favorneoplasia(specifyendocervicalornototherwisespecified)
¨ Adenocarcinoma
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Table3:EvolutionofCervicalCancerPrecursors(58)
CINgrade Regression Persistence ProgressiontoCIN3
Progressiontowardsinvasivecancer
CIN1 57% 32% 11% 1%
CIN2 43% 35% 22% 5%
CIN3 32% <56% - >12%
Table4.CriteriaforAblativeMethodsofCINTreatment
ModifiedfromPrendiville2009(61)(permissionrequested)
Ø Thetransformationzone(TZ)mustbefullyvisible
Ø AcolposcopicallydirecteddiagnosticbiopsymustbetakenfromthemostdysplasticareaintheTZ
Ø Theremustbenosuspicionofinvasivedisease
Ø Theremustbenosuspicionofglandulardisease
Ø Thereshouldnotbecytological/histologicaldisparity
Ø Thepatientshouldnothavehadprevioustreatment
CryotherapyisnotrecommendedfortreatmentofCIN3
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Figure1.TransformationZoneCategories
Type I Type II Type III
completely ectocervical
fully visible
small or large ectocervical component
has an endocervical component
fully visible
may have ectocervical component which may
be small or large
has an endocervical component
is not fully visible
may have ectocervical component which may
be small or large
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Glossary
AC AdenocarcinomaAGC-N Atypicalglandularcells-favorneoplasiaAGC-NOS Atypicalglandularcells-nototherwisespecifiedAGUS AtypicalglandularcellsofundeterminedsignificanceAIS AdenocarcinomainsituASC-H Atypicalsquamouscells-cannotexcludehigh-grade
squamousintraepitheliallesionASCUS AtypicalsquamouscellsofundeterminedsignificanceCIN(1,2,3) Cervicalintraepithelialneoplasia(1,2,3)ECC EndocervicalcurettageHPV HumanpapillomavirusHSIL High-gradesquamousintraepitheliallesionLEEP/LLETZ Loopelectrosurgicalexcisionprocedure/largeloop
excisionofthetransformationzoneLSIL LowgradesquamousintraepitheliallesionSCC Squamouscellcarcinoma