SOGC / SCC Clinical Practice Guideline -...

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

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

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)

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)

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)

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

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.

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)

2SeeTable2fordescriptionoftheseterms.

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)

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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)

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)

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)

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)

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)

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)

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)

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)

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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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)

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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)

Recommendations

WaitTimesforColposcopy5. WomenwithHSILareideallyseeninacolposcopyclinicwithin4weeksof

referral.(III-C)

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TheColposcopyExam5. Colposcopicfindingscanbedescribedaccordingtotheterminologydefined

bytheInternationalFederationforCervicalPathologyandColposcopy.(III-C)

ManagingwomenwithASCUSorLSILonreferraltoColposcopy3. Acolposcopicallyidentifiedlesionshouldbebiopsied.(III-C)

ManagingASC-H3. AwomanwithanASC-HPaptestshouldhavecolposcopytoruleoutCIN2/3

and/orcancer.(II-2A)

ManagingHSIL3. AllwomenwithanHSILtestresultshouldhavecolposcopy.(II-2A)

ManagingAtypicalGlandularCytology(AGC-NOS,AGC-N,AIS)3. ThefindingofanAGCPaptestwarrantscolposcopy.(II-2A)

ManagingSCCandAdenocarcinoma2. Womenwithacytologicdiagnosissuggestiveofcarcinoma,withorwithouta

visiblelesion,shouldhavecolposcopy.(IIIA)

ManagingthePatientwithAbnormalHPVTestandNormalCytology2. WomenwhotestpositiveforHR-HPVandhavenegativecytologyshould

haverepeattestingat12months.PersistentpositiveHR-HPVtestswarrantcolposcopy.(IA)

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ManagingAbnormalCytologyinPregnancy4. WomenwithanASCUSorLSILtestresultduringpregnancyshouldhave

repeattestingpostpregnancy.(III-B)

ManagingAbnormalCytologyintheAdolescent4. Screeningshouldnotbeinitiatedinwomenlessthan21yearsofage.(II-2A)

ManagingHistologicalAbnormalities

ManagingCIN13. BiopsyprovenCIN1shouldbeobservedwithrepeatcolposcopyat12-month

intervals.Persistencebeyond24monthsmaybetreatedorobservedwithrepeatcytologyand/orcolposcopy.(II-1B)

ManagingCIN2/33. CIN2or3shouldbetreated;excisionalproceduresarepreferredforCIN3.

(II-1A)

4. Womenwhohavepositivemarginsshouldhaveclosefollow-upwithretreatmentwithexcisionforpersistentdisease.(II-1B)

ManagingCIN2/3intheAdolescent3. CIN2intheadolescentpatientshouldbeobservedwithcolposcopyat6-

monthintervalsforupto24monthsbeforetreatment.(II-2B)

ManagingAdenocarcinomainSitu(AIS)5. IfAISisdiagnosed,treatmentneedstobedonewithadiagnosticexcisional

procedure,ortype3TZexcision.(II-2A)

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ManagingHistologicalAbnormalitiesDuringPregnancy2. IfCIN2orCIN3isdiagnosedduringpregnancy,treatmentshouldbedelayed

untilafterdelivery.(II-2A)

Follow-upPostTreatment3. Post-treatmentforCIN2or3:womenshouldbefollowedwithcytologyand

colposcopyat6monthintervalsfortwovisits,aslongasbothcytologyandanybiopsiesarenegative.(II-2B)

ManagingHistologicalAbnormalitiesinHigh-RiskIndividuals3. Immunocompromisedwomenshouldbescreenedannuallybutnotwith

colposcopy.(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

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