Asccp Updated Guidelines - 3.21.13

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2012UpdatedConsensus
GuidelinesfortheManagementof
AbnormalCervicalCancer
ScreeningTestsandCancer
Precursors
L.StewartMassad,MD,MarkH.Einstein,MD,WarnerK.Huh,MD,
HormuzdA.Katki,PhD,WalterK.Kinney,MD,MarkSchiffman,MD,
DianeSolomon,MD,NicolasWentzensen,MD,andHerschelW.Lawson,MD,
forthe2012ASCCPConsensusGuidelinesConference
FromWashingtonUniversitySchoolofMedicine,St.Louis,Missouri;AlbertEinsteinColle
geof
Medicine,NewYork,NewYork;UniversityofAlabamaSchoolofMedicine,Birmingham,
Alabama;DivisionofCancerEpidemiologyandGeneticsandDivisionofCancerPrevention
,
NationalCancerInstitute,Bethesda,Maryland;ThePermanenteMedicalGroup,Sacrame
nto,California;andEmoryUniversitySchoolofMedicine,Atlanta,Georgia
h ABSTRACT: Agroupof47expertsrepresenting23
professionalsocieties,nationalandinternationalhealth
organizations,andfederalagenciesmetinBethesda,MD,
September1415,2012,torevisethe2006AmericanSociety
Y
forColposcopyandCervicalPathologyConsensusGuidelines.
Thegroupsgoalwastoproviderevisedevidence-based
consensusguidelinesformanagingwomenwithabnormal
cervicalcancerscreeningtests,cervicalintraepithelialneoplasia(CIN)andadenocarcinomainsitu(AIS)following
adoptionofcervicalcancerscreeningguidelinesincorporatinglongerscreeningintervalsandco-testing.Inadditionto
literaturereview,datafromalmost1.4millionwomeninthe
KaiserPermanenteNorthernCaliforniaMedicalCarePlan
providedevidenceonriskafterabnormaltests.Wheredata
wereavailable,guidelinesprescribedsimilarmanagement
forwomenwithsimilarrisksforCIN3,AIS,andcancer.Most
priorguidelineswerereaffirmed.Examplesofupdatesinclude:Humanpapillomavirus Ynegativeatypicalsquamous
cellsofundeterminedsignificanceresultsarefollowedwith
co-testingat3yearsbeforereturntoroutinescreeningand
arenotsufficientforexitingwomenfromscreeningatage
65years;womenaged21 Y24yearsneedlessinvasivemanagement,especiallyforminorabnormalities;postcolposcopy
managementstrategiesincorporateco-testing;endocervical
samplingreportedasCIN1shouldbemanagedasCIN1;
unsatisfactorycytologyshouldberepeatedinmostcircumstances,evenwhenHPVresultsfromco-testingareknown,
whilemostcasesofnegativecytologywithabsentorinsufficientendocervicalcellsortransformationzonecomponent
canbemanagedwithoutintensivefollow-up.
h
Theseguidelinesarebeingpublishedsimultaneouslyin
Obstetrics&
Gynecology andthe JournalofLowerGenitalTractDisease .Thecomplete
algorithmsarepublishedinthe JournalofLowerGenitalTractDisease
and
arealsoavailableonthewebsiteoftheAmericanSocietyforColposcopy
andCervicalPathology(http://www.asccp.org/).
Thecontentsofthisarticlearesolelytheresponsibilityoftheauthors
anddonotnecessarilyrepresenttheofficialviewsoftheNationalInstitutes
ofHealthorU.S.federalgovernment.Correspondingauthor:L.Stewart
Massad,MDDivisionofGynecologicOncology,WashingtonUniversity
y2001,revisedBethesdasystemterminologyfor
SchoolofMedicine,4911Barnes-JewishHospitalPlaza,St.Louis,MO63110;e-mail:massadl@wudosis.wustl.edu.
reportingcervicalcytologyresultsandtheavailabilityoffindingsfromarecentrandomizedtrialofstrategies
FinancialDisclosure
Dr.Massadhasservedasanexpertwitness.Dr.Huhasservedasa
formanagingminorcervicalcytologicabnormalitieshad
consultanttoRoche.Dr.SchifmanhasresearchedreagentsforQiagenandRoche.Theotherauthorsdidnotreportanypotentialconf
lictsofinterest.
createdtheneedforastandardapproachtomanaging
womenwithabnormalcervicalcytologyandcervical
cancerprecursors(13).Inresponse,theAmericanSociety
Y
! 2013,AmericanSocietyforColposcopyandCervicalPathology
JournalofLowerGenitalTractDisease,Volume17,Number5,2013,S1
YS27
forColposcopyandCervicalPathology(ASCCP)initiated
S2
&
MASSADETAL.
aprocessthatdevelopedcomprehensive,evidence-based
consensusguidelinestoaidcliniciansinmanaging
womenwithabnormalcervicalcytology,cervicalintraepithelialneoplasia(CIN),andadenocarcinomainsitu
(AIS)(4,5).Althoughthoseguidelinesbecamethestandardformanagingwomenwithabnormalcervicalcytologyandcancerprecursors,theneedforrevisionsbecame
apparent.Asecondconsensusconferencein2006aligned
managementofminorcytologicabnormalitiesandCIN1,
incorporatedfollow-upresultsoftheASCUS-LSILTriage
Study(ALTS),identifiedstrategiesformanagementof
positivehumanpapillomavirus(HPV)DNAtests,and
establishedguidelinesformanagementofadolescentsand
youngwomen(6,7).
Asupdatedin2001,theBethesdaSystemalsodefined
terminologyforcytologicspecimenadequacy,andASCCP
developedmanagementguidelinesforwomenwithunsatisfactorycytologyresultsandforthosewithnegativeresults
butlimitedendocervical/transformationzone(EC/TZ)
component(8).Theseguidelineswereupdatedin2008(9)
butwerenotvalidatedbyanationalconsensusconference.
Previousguidelinesremainvalid,butknowledge
hasadvanced.Screeninghaschanged.In2012,national
organizationspublishedguidelinesembracinglonger
screeningintervalsandalateragetostartscreening
(10,11).Co-testingwithcytologyandHPVtestingat
5-yearintervalsisnowthepreferredoracceptable
strategyforcervicalcancerscreeningforwomenaged
30Y64years(10,11).Cliniciansshouldbenefitfrom
guidanceonhowtoincorporateco-testingintomanagementofwomenwithcervicalabnormalities.
Inaddition,newevidencetoguidedecisionsabout
managementofabnormalscreeningtestsandCINand
AISemergedin2012fromanalysesofthelargeclinical
databaseattheKaiserPermanenteNorthernCalifornia
MedicalCarePlan(KPNC),conductedincollaboration
withscientistsfromtheNationalCancerInstitute(NCI)
(12).Thisnewevidencefillsgapsinthe2006guidelines.
Forexample,priormanagementguidelinesreliedheavily
ondatafromALTS,whichprovidedevidenceoninitial
managementofwomenwithminorcytologicabnormalities.Resultswereextrapolatedtoprovideguidelineson
managementofwomenwithmoreseverecytologicabnormalitiesandpost-colposcopyfollow-up.Thenewer
evidencefromKPNCanalysesallowsvalidationor
modificationofpriorguidelinesinspecificareas.The
sizeoftheKPNCdatabasealsoallowsage-based
stratificationofdataforsometypesofabnormalities.
WhiletheseobservationaldatafromasingleU.S.regionmaylimitgeneralizabilityandthelackoffollow-up
beyond8yearsmaylimitlong-termriskestimates,publicationofcomparableanalysesfromsimilarlylargedatabasessoonisunlikely.
Finally,additionaldatahaveemergedinspecificareas.
Humanpapillomavirusgenotypingtestshavebeenapproved;thesehavebeenrecommendedasanoptionfor
specificclinicalscenariostoguidetriagetocolposcopy.
Moreinformationisalsoavailabletoguidemanagement
ofwomenwithunsatisfactorycytology.
Inresponse,ASCCPconductedaconsensusprocessto
updatethemanagementofabnormalco-testingresultsand
cytologywithspecimenadequacylimitations,theinitial
managementofabnormalscreeningtestresults,optionsfor
postcolposcopymanagement,managementofwomen
aged21 Y24years,andotherissues.Thisreportdetailsthe
consensusguidelinesdevelopedthroughthisprocess.
METHODS
Theprocessforthe2012consensusguidelineswas
similartothatforthepreviousguidelines(4
Y7).Initially
theASCCPPracticeCommitteedefinedquestionsforthe
2012consensusprocess.Asteeringcommitteeofnationallyrecognizedexpertsincervicalcancerprevention
wasnominatedandcanvassedforadditionalquestions.
AttheMarch2012ASCCPBiennialScientificMeeting,
conferenceattendeespresentedsuggestionsforguidelinesreview.Organizationsthatparticipatedinthe2006
guidelinesdevelopmentprocessweresolicitedtonominaterepresentativestotherevisionprocessandalsowere
askedtoidentifyquestionsforreview.Participantsand
participatingorganizationsarelistedinAppendixA.
Amultifacetedprocesswasusedtoevaluatetheevidenceandresolveidentifiedissues.Fiveworkinggroups
werecreated,chairedbysteeringcommitteemembers
andincludingdelegatesfromparticipatingorganizations.
Forsomeworkinggroups,theMEDLINEdatabasewas
queriedusingrelevantkeywordsforEnglish-language
articlespublishedafter2005,thedateofthelastconsensusconferencereview(seeAppendix1,available
onlineathttp://links.lww.com/LGT/A9).Potentiallyrelevantabstractsfromidentifiedarticleswerereviewed.
Reportswereratedaccordingtothestrengthandquality
ofrelevantevidence.
Otherworkinggroupsfocusedonanalysesofoutcomes
riskfromadatabaseof1.4millionwomencaredforat
KPNCandfollowedfromJanuary1,2003toDecember
31,2010.Theprimaryoutcomeofinterestintheseanalyses
wasCIN3+(CIN3,AIS,andcancer).Cancerwasusedas
anoutcomewhenriskwashighandCIN2+(CIN3+and
ASCCPGuidelinesUpdate
CIN2)wasusedwhenthenumberofCIN3+eventswas
low.Applyingtheconceptsofsimilarmanagementfor
similarrisks,riskswerebenchmarkedtothoseforacceptedmanagementstrategies.Sincedelegatesconsidered
zerocancerriskunattainableandCIN3+areasonable
proxyforcancerrisk,acceptableriskswereconsidered
tobethoseapproximatingCIN3+risk3yearsafter
negativecytologyor5yearsafternegativeco-testing.In
brief,immediatecolposcopywasrecommendedwhenthe
5-yearriskofCIN3+intheKPNCcohortexceeded5%,a
6-monthto12-monthreturnforriskof2
Y5%,a3-year
returnforriskof0.1 Y2%,anda5-yearreturnintervalfor
riskcomparabletoco-testinginwomenwithoutahistory
ofabnormality,or0.1%.(12).
Draftguidelinesdevelopedbytheworkinggroupswere
postedtotheASCCPwebsite,andcommentswere
solicitedfromcollaboratingorganizationsandthepublic.
Draftguidelinesrevisedinlightofpubliccommentswere
presentedtoaconsensusconferenceconvenedSeptember
14Y15,2012,attheNatcherConferenceCenteronthe
campusoftheNationalInstitutesofHealthinBethesda,
MD.Draftguidelinesandsupportingevidencewerepresented,discussed,revisedasneeded,andadoptedbyatleast
66%ofvotingdelegatesusingelectronicvotingdevices.
Theterminologyusedintheupdatedguidelinesis
similartopriorversions,andthetwo-partratingsystem
isthesame(Table1).Ratingsaregiveninparentheses
throughouttheguidelines.Theterms
preferred,acceptable,andunacceptable recommended,
areusedinthe
guidelinestodescribevariousinterventions.Anewterm,
notrecommended ,wasaddedtodescribemanagement
strategieswithweakevidenceagainsttheirusebutonly
marginalriskforadverseconsequences.Thestrengthrating
ofarecommendationwasbasedonthequalityofevidence
supportingitbutincorporatedotherfactors,including
potentialforharmifaninterventiondidnotoccurand
potentialcomplicationsfromagivenintervention.
Forcytologicclassificationandassessmentofcytology
specimenadequacy,the2001BethesdaSystemwasused
(1).Forhistologicclassification,atwo-tieredsystemwas
employed.Low-gradelesionsweretermedCIN1andhighgradelesionsweretermedCIN2orCIN3.SomepathologistsdonotdistinguishCIN2fromCIN3,andthese
undifferentiatedhigh-gradelesionsaretermedCIN2,3.
GUIDINGPRINCIPLES
Participantsattheconsensusconferenceaffirmedthat
the2006ASCCPguidelinesforthemanagementof
abnormalcervicalcancerscreeningtests(6)andCIN
&
S3
Table1.RatingtheRecommendations
Strengthofrecommendation*
AGoodevidenceforefficacyandsubstantial
clinicalbenefitsupportrecommendationforuse.
BModerateevidenceforefficacyoronlylimited
clinicalbenefitsupportsrecommendationforuse.
CEvidenceforefficacyisinsufficienttosupportarecommendationfororagainstuse,butrecommendati
bemadeonothergrounds.DModerateevidenceforlackofefficacyorforadver
EGoodevidenceforlackofefficacyorforadverse
outcomesupportsarecommendationagainstuse.
Qualityofevidence*IEvidencefromatleastonerandomized,controlledtrial.IIEvidencefromatleaston
randomization,fromcohortorcase-controlled
analyticstudies(preferablyfrommorethan
onecenter),orfrommultipletime-seriesstudies,
ordramaticresultsfromuncontrolledexperiments.
IIIEvidencefromopinionsofrespectedauthorities
basedonclinicalexperience,descriptivestudies,
orreportsofexpertcommittees.
Terminologyusedforrecommendations
RecommendedGooddatatosupportusewhenonlyone
optionisavailable.
PreferredOptionisthebest(oroneofthebest)when
therearemultipleoptions.
AcceptableOneofmultipleoptionswhenthereiseither
dataindicatingthatanotherapproachis
superiororwhentherearenodatatofavoranysingleoption.NotrecommendedWeakevidenceagainst
UnacceptableGoodevidenceagainstuse.
*ModifiedfromGrossPA,BarrettTL,DellingerEP,etal.Purposeofqualitystandardsfor
infectiousdiseases.InfectiousDiseasesSocietyofAmerica.ClinInfectDis1994;18:421.
98.KishMA.Guidetodevelopmentofpracticeguidelines.ClinInfectDis2001;32:851
Theassignmentofthesetermsrepresentsanopinionratifiedbyvoteduringthe2012
consensusconference.
Y4.
orAIS(7)remainvalid,withtheexceptionofthespecificareasreviewed.Thoseearlierguidelineshavebeen
combinedwithcurrentrevisionsinthisdocumentto
providecomprehensiverecommendationsformanagement.ChangesaresummarizedinBox1.
Cervicalcancerpreventionisaprocesswithbenefits
andharms.Riskcannotbereducedtozerowithcurrentlyavailablestrategies,andattemptstoachievezero
riskmayresultinunbalancedharms,includingovertreatment.Asnotedina2011consensusconferenceon
cervicalcancerscreening(10),optimalpreventionstrategiesshouldidentifythoseHPV-relatedabnormalities
likelytoprogresstoinvasivecancerswhileavoidingdestructivetreatmentofabnormalitiesnotdestinedtobecomecancerous.Adoptedmanagementstrategiesprovide
whatparticipantsconsideredanacceptablelevelof
riskoffailingtodetecthigh-gradeneoplasiaorcancer
inagivenclinicalsituation.Wheredatawereavailable,
S4
&
MASSAD ET AL.
Box 1. Essential Changes From Prior Management

Guidelines*
& Cytology reported as negative but lacking endocervical cells can be
managed without early repeat.
& CIN 1 on endocervical curettage should be managed as CIN 1, not as a
positive ECC.
& Cytology reported as unsatisfactory requires repeat even if HPV negative.
& Genotyping triages HPV-positive women with HPV type 16 or type
18 to earlier colposcopy only after negative cytology; colposcopy is
indicated for all women with HPV and ASC-US, regardless of
genotyping result.
& For ASC-US cytology, immediate colposcopy is not an option. The serial
cytology option for ASC-US incorporates cytology at 12 months, not
6 months and 12 months, and then if negative, cytology every 3 years.
& HPV-negative and ASC-US results should be followed with co-testing at
3 years rather than 5 years.
& HPV-negative and ASC-US results are insufficient to allow exit from
screening at age 65 years.
& The pathway to long-term follow-up of treated and untreated CIN 2+
is more clearly defined by incorporating co-testing.
& More strategies incorporate co-testing to reduce follow-up visits. Pap-only
strategies are now limited to women younger than 30 years, but
co-testing is expanded even to women younger than 30 years in some
circumstances. Women aged 21-24 years are managed conservatively.
CIN, cervical intraepithelial neoplasia; ECC, endocervical curettage; HPV, human papillomavirus; ASC-US, atypical squamous cells of undetermined significance.
*Prior management guidelines were from the 2006 Consensus Guidelines for the
Management of Women With Abnormal Cervical Screening Tests (6). Prior guidelines
not changed were retained.
similar management strategies were prescribed for similar levels of risk (12, 13). Guidelines cannot be developed for all situations. Clinical judgment should always
be applied when applying guidelines to individual patients. This is especially true for guidelines based on less
robust evidence.
In 2012, the Lower Anogenital Squamous Terminolog y(LAS T)P rojec tcreatedne wtermino logyforHPVre lated les ionso fthelowerg enitaltr act(14).Howev er,
de legat est othec urrentcons ensuspro cessdetermine d
th atthi scl assif icationdoe snotyeth aveasufficien tly
ro busto utc omese videncebas etoallow elucidationof
ri sk-ba sed manag ementguide lines(se eBox2).
Algorithms detailing the different management recommendatio nsareavai lab leattheAS CCPwebsite
(www.asccp .org/cons ens us2012).A glossaryof terms
usedintheg uidelines isi nAppe
ndix B.
In the 2006 ASCCP guidelines,(6,7) several pathways
concluded by returning women to routine screening.
This term was not defined, but in 2006, screening
guidelines prescribed cytology at shorter intervals than
now recommended. Current 2011 screening guidelines
recommend either 3-year cytology intervals or, for
women aged 30Y64 years, 5-year co-testing intervals
(10, 11). These multi-year intervals are safe only when
risk for the development of CIN 3+ during the years
between testing is low (10, 11). For example, women
aged 30Y64 years with a negative co-test have a 5-year
risk of CIN 3+ of only 8/10,000 (12). Although this low

level of risk can be achieved among women with negative screening histories, for those with some abnormalities, risk for CIN 3+ remains elevated for years, even
after treatment and even after initial negative surveillance. After some abnormalities, current follow-up data
are insufficient to define a pathway to return to 5-year
routine screening intervals because even with treatment,
risk does not fall to a level consistent with 5-year retesting.
When, how, and even whether to perform endocervicalsa mpli ngi scon trovers ia l.Endoc ervicalbrushin ghas
bette rsen sit ivit ythancu re ttagewi thsimilarspeci ficity,
bette rtol era nce, andfewe ri nsuffic ientsamples,al thoug
hgra ding may bemo rediffi cu ltbecau sestromaisrare ly
sampl edwi thb rush ing(15, 16 ).Eithe risacceptable
foren doce rvi cals ampling .I n2006,w orkinggroups
asses sing man agem entofcy to logyrep ortedasatypica l
squam ousc ell sofu ndeterm in edsigni ficance(ASC-US )
andlo w-gr ade squa mousint ra epithel iallesions(LSI L)
defin edin dic atio nsforen do cervica lsampling,guid ance
thats houl dbe vali dforwom en withcyt ologyresults
ofaty pica lsq uamo uscells ,c annotex cludehigh-grad e
squam ousi ntr aepi thelial le sions(A SC-H)andhigh-g rad
esqu amou sin trae pitheli al lesions (HSIL)aswell.
Management strategies incorporate HPV testing based

onstudiesu singvalida tedHPVassay s.M anageme nt
basedonres ultsofHPVt estsnotsimi lar lyvalid atedmay
notresulti nintendedo utcomesandm ayr iskpati ent
harm.These guidelines areintended for useonly with
HPVteststh athavebeen analyticall yan dclinic allyvali datedwithp rovenaccep tablereprod uci bility, clinical sensitivity,s pecificity ,andpositiv ean dnegati vepredic tive
valuesforc ervicalcan cerandverif ied precanc er(CIN2+ ),
asdocument edbyU.S.Fo odandDrugAd min istrati on
(FDA)licen singandapp rovalorpubl ica tioninp eerreviewedsc ientificli terature.Te sti ngshoul dberestr icted
tohigh-ris k(oncogeni c)HPVtypes( mai nly16,1 8,31,33,
35,39,45,5 1,52,56,58 ,and59),and int hesegui delinesHPV testingr efersonlyto tes tingfor high-ris k
Box 2.
A recent consensus conference (the Lower Anogenital Squamous
Terminology [LAST] Project convened by the College of American
Pathologists and the American Society for Colposcopy and Cervical
Pathology) adopted a two-tier terminology that incorporates ancillary
tests and other criteria to distinguish indeterminate lesions as high grade
or low grade. Until a comprehensive evidence review and consensus
guidelines development process can be conducted, histopathology
results reported as low-grade squamous intraepithelial lesions (LSIL)
should be managed as cervical intraepithelial neoplasia (CIN) 1 and
those reported as high-grade squamous intraepithelial lesions
(HSIL) should be managed as CIN 2,3 (14).
ASCCP Guidelines Update
(oncogenic) HPV types. Testing for low-risk (nononcogenic)

HPV types has no role in the evaluation of women with
abnormal cervical cytologic results.
Both ablation and excision effectively treat CIN.
Randomized trials comparing different modalities show
similar efficacy (17Y20). Efficacy rates range from 90%
to 95%, and most failures occur within 2 years (21),
although cancers can develop up to 20 years after
treatment (22). Margin status is a convenient predictor
of recurrence and a traditional risk marker, although it
does not appear to be an independent risk factor (23,
24). Nonsurgical therapies, including topical agents and
therapeutic vaccines, remain investigational.
A wide variety of follow-up approaches have been
d escr ibedfor wo mentreate dforCIN,in corp orating
c ytol ogy,HPV te sting,and colposcopy alon eorin
c ombi nationa ti ntervalsf rom3months toan nually.
H PVte stingis mo resensiti vebutlesss peci ficthancyt olog yinpost tr eatmentfo llow-upand itma yresultin
&
S5
future pregnancies. Young women have high regression

rates for cervical disease and low cancer risk (31Y33).
The term young women indicates those who after
counseling by their clinicians consider risk to future
p r e g n a n c i e s f r o m t r e a t i n g cervcial abnormatiels to
outweigh risk for cancer during observation of those
abnormalities. No specific age threshold is intended.
In 2006, guidelines recommended less aggressive
ma nagem entforadol escentswith cerv icalabnormalit
ie s(6, 34),butthe searenowmoo tbec ausethe2011
sc reeni ngguidelin esrecommend nots creeningadoles
ce nts(1 0,11).Dele gatestothe2 012c onsensusconferen cecon sideredles sintensivem anag ementforother
yo ungwo menwithabn ormalcytolo gy.C ervicalcanc
er
ri skrem ainslowthr oughage25ye ars( 35),HPViscommon(36), and l
21Y24 years is 1.4/100,000, and almost 55,000 cytology

tests must be obtained for every cervical cancer diagearlier diagnosis of persistent or recurrent disease (25). nosed in this age group (35). This level of risk is 10-fold
Protocols for follow-up after treatment of CIN have higher than risk in adolescents and appears to be high
not been evaluated as primary interventions in ran- enough to justify screening yet is low enough to allow
domized trials.
observation for minor cytologic abnormalities. GuideUnder the 2011 screening guidelines, women lines for women aged 21Y24 years can be extrapolated
follo wed afte rpositive HPVtestsbut negativecyto to adolescents inadvertently screened.
logy
Interventions for abnormal screening tests and CIN
werer efe rred tocolposc opyonlyifth eyhadLSILor
orAIShaveothe rco nsequenc esthatare notea sil y
mores eve recy tologyora positiveHPV testduring
measurable.Wo men experien ceemotion aldis tre sswhe
surve ill ance co-testin g(10).Howev er,only0.04
n
%ofal l
receivingabno rma lcytolog yandHPVte stres ult s,whe
women age d30- 64yearsin theKPNCdata baseha
n
d
havingcolposc opy evenwhen findingsa renor mal ,and
HPV-n ega tive ASC-USaft eranHPV-pos itive,cyt
whenundergoin gce rvicaltr eatment.E motio nal distre
ology
ss
negat ive resu lt(26),so referringth esewomenforcol -pos copywill bur denca res ystemsmi nimally.Thus, forsimp li city,cu
isusuallyprom pte dbyuncer taintyand antic ipa tionof
theunknown(38 ).M anymanag ementstra tegie sin corporatefollow- upw ithHPVte sting,whi chcan eli cit
Studies of the effect of treatment on future pregnancy feelingsofsti gma andshame whenposit ivede spi tethe
near-ubiquito usf requency ofHPVinfe ction (39 ,40).
areconf li cti ng,alt ho ughmanyin di catean approxiTheanxietyand tim erequire dforvisit stoma nag eabmatelyt wo -fo ldincr ea seinprete rm delive ryrisk
normalcytolog yca nadverse lyaffectr elati ons hips,
(27Y29). Although not proven, this is presumed to re- work-relateda nds choolact ivities,a ndfam ily matter s
sult from deficient cervical stroma, and risk appears to (41).Thesepot ent ialharms reinforce theco nce ptthat co lpos copya
increase with the volume and number of excisions (30).
However, many studies were done in countries where
loop excisions are performed with larger loop sizes and
deeper excisions than most U.S. clinicians employ.
Studies linking ablative treatments to preterm delivery
are even more limited and conflicting. Women with
CIN may be at increased risk for preterm delivery even
when untreated. Nevertheless, because pregnancy
complications can be devastating, the potential benefits
of treatment should be balanced against the risk to
In the 2001 guidelines (4), separate recommendations

fo rAS C-US management were develope dforwomen
in fec tedw ithhumanim muno deficien cyvirusandother
im mun osup pressiveco ndit ions.Dat areviewin2006
el imi nate dthesesepa rate guidelin es.Immunosuppressed
wo men with abnormalre sult sshouldb emanagedinthe
sa mem anne rasimmunoc ompe tentwome n.
S6
&
MASSAD ET AL.
Guidelines on management apply only to women un- other processes (44, 45). Now that most U.S. cytology is
dergoingro ut inescreeni ngwit hade qu atevi sualizationo done using liquid-based media, which can control for
f
most obscuring factors in processing, unsatisfactory rethecervixa nd directedsa mplin gwit ha ccept ablecollecsults arise largely from insufficient squamous cells (46).
tioninstru me nts.Theyal soapp lyon ly towom enidentifiedwith ab normalitie sduri ngsc re ening .Womenwith Evidence is sparse governing management of women with
postcoital or unexplaine dabno rmal va ginal bleeding,
unsatisfactory cytology obtained as part of co-testing,
pelvicpain ,a bnormaldis charg e,or av isibl elesionmerit indivi
dualizede
although
riskvalu
for ations.
high-grade disease in women with
Consensus guidelines from the ASCCP have internationalinf luence.How ever ,th eyare tail oredtotheopportunist iccervical canc ers creen ings ystemofthe
UnitedSta tes,withsp ecif ict ermin olog y,diagnosticcri teria,pat hwaystocol posc opi ctrai ning ,patientexpectations and adherence, and medicalYlegal risks. Clinicians
elsewhere must consider the guidelines in light of their
own context and adapt management accordingly.
negative HPV tests appears to be low (47). Unsatisfactory

results arise largely from insufficient squamous cells (48).
Some currently available HPV tests lack a control for
epithelial cellularity, so a negative HPV test cannot be
relied, upon as the HPV test may be falsely negative because of an insufficient sample.
Specimen collection techniques to minimize unsatisfactoryc ytologyhav enotchange ds incethel astguideline
(9).Exte nded-tipsp atulas,spa tu lasplusb rushes,and
broomsal lappeareff ective(49, 50 ).Whentw odevices
areused, theectocer vicaldevic es houldbeu sedfirst.
MANAGEMENT OF ABNORMAL SCREENING TESTS

Unsatisfactory Cytology
Cytology results are unsatisfactory for 1% or less across
allprepa rationt ype s(42,43).Unsat isf ac to rycy tology
specimen sareunr eli ablefordetecti nge pi th elia labnormalities .Howeve r,m oststudiesthat fou nd ah ighe rrisk
ofdiseas eamongw ome nwithunsatisfa cto ry cy tolo gy
employed convent ion alPapteststhat can be re nder ed
unsatisf actoryb yob scuringblood,i nfl am ma tion ,or
Figure 1.
Management of Women With

Unsatisfac to ryCyt ology(Fig.1)
Forwomenwi th anuns atisfactorycytology resultan d
no,unknown ,o raneg ativeHPVtestresult, repeatcy tology in 2Y4 months is recommended (BIII). Triage
using reflex HPV testing is not recommended (BIII).
Treatment to resolve atrophy or obscuring inflammation
when a specific infection is present is acceptable (CIII).
For women aged 30 years and older who are co-tested

and have unsatisfactory cytology and a positive HPV
test, repeat cytology in 2Y4 months or colposcopy is
acceptable (BII). Colposcopy is recommended for women
with two consecutive unsatisfactory cytology tests (CIII).
Cytology Reported as Negative but With

Absent or Insufficient EC/TZ Component
&
S7
CIN 3+ risk (53). A recent meta-analysis found that

negative cytology had good specificity and negative
predictive value despite absent or insufficient EC/TZ
component (54). HPV testing appears to be independent
of transformation zone sampling (55) and offers an
added margin of safety for women aged 30Y64 years
now that co-testing is the preferred screening strategy
for that age group. An absent EC/TZ component is not
associated with an increased incidence of cervical disease after treatment of CIN 2+ (56).
Cytology reported as negative but with absent or insufficie ntEC/TZc om ponentha sad equa tecell ul arit
y
Management of Women With Cytology Reported as
forinter pretatio nb utlackse ndo cerv icalor me taplast
Negative but With Absent or Insufficient EC/TZ
ic
Component (Fig. 2)
cells,su ggesting th atthesqu amo colu mnarju nc tion
may
For women aged 21Y29 years with negative cytology and
nothaveb eenadequ at elysampl ed. This raises co ncer absent or insufficient EC/TZ component, routine screenn
formisse ddisease .R ecentlyr epo rted rateso fc ytolog ing is recommended. HPV testing is unacceptable (BIII).
For women aged 30 years and older with cytology
y
resultsr eporteda sn egativeb utw itha bsento ri nsuffi- rep orted asne ga tivea ndw ithab sent orinsufficie
cientEC/ TZcompon en thaveran ged from 10%to2 0 nt
EC/ TZcom pone nt andno oru nknow nHPV testre
%
andarehi gherinol de rwomen(5 1,5 2).P riorgu id elin sul t,HPV test in gispr efe rred( BIII ).Repeatcytolo
es
recommen dedearly re peatcyto log y(8, 9).How ev er, gyi n
3ye arsis acce
pt oncurrent
ablei fHP cyt
Vtest
ingi snotperforme
whilewom enwithab se ntorinsu ffi cien tEC/TZ co m-ponenthavef
ewerc
ologicab
normalities,th eydonothave
d
(BI II).I fthe HP Vtest isd onean disn egative,return to ro utines
Figure 2.
S8
&
MASSAD ET AL.
recommended (BII). If HPV type 16 and type 18

are absent, repeat co-testing in 12 >months is recommended (BIII).
Negative Cytology With a Positive HPV Test
Management of Women Testing HPV Positive but

Cytology Negative (Fig. 3)
For women 30 years of age and older with HPV-positive
but cytol og y-neg at ive co- testi ng,r epeatco-testinga t
1ye arisa cc eptab le (BI I). Atthe 1-ye arrepeatco-test, if
the HPVte st ispos it ive orc ytolo gyis ASC-USorworse,
col posco py isrec om men ded (BII) .Ift he1-yearrepeat
co- testr es ultis HP Vne gat ivean dcyt ologynegative,
rep eatco -t estin gi n3y ear sisre comm ended(BII).
Although not indicated for younger women, co-testing is

the preferred screening strategy for women aged 30Y64
years (10). Despite negative cytology, women with oncogenic HPV are at higher risk for later CIN 3+ than
women with negative HPV tests (57). The risk of CIN 3+
HPV genotyping is also acceptable. If HPV-16 or
in HPV positive but cytology negative women is suffi- HPV -18testsar ep osit ive,colposc op yisrec ommende
cient to justify early return for retesting. Persistent HPV d
(BI I).IfHPV-1 6a ndHP V-18testsar en egativ e,repeat co-te sti n
positivity increases risk still further (58, 59). However,
most HPV infections are cleared, substantially reducing risk of CIN 3+ (60), so observing women to allow
Atypical Squamous Cells of Undetermined
clearance is attractive. Nevertheless, CIN 3+ does occur
Significance (ASC-US)
during observation, requiring guidelines to balance risks
arising from intervention for HPV that may yet be cleared ASC-US is the most common cytologic abnormality, but
against the risks of disease. This is true even for women itcarr ie sth elow estris kofCIN3+, partlybecaus eone
thirdt ot wot hird sareno tHPV-asso ciated(2,26) .In
with HPV infections but negative cytology. In the KPNC
ALTS,t hr eem anag ements trategies performedsim ilarly
cohort, the CIN 3+ risk for every co-test result obtained andwer ei ncl uded insubs equentgui delines(3,4, 6).
after an initial HPV-positive but cytology-negative result Compar ed wit hcol poscop yforallAS C-US,reflext estwas higher than risk associated with that co-test result in ingfol lo wed byco lposco pyforHPV- positivewome n
waspre fe rre dbec auseit identifie dmostCIN3les ions
women with prior negative screening (58).
yetref er red many fewerw omentocol poscopy(3).A LTS
Women with HPV-16 are at particular risk for CIN wascon du cte dbef orethe 2001Bethe sdasystemupd ate,
3+.Hu manp apillo mav ir us-18merit sspe cia lconsid er whichs ep ara tedA SC-Hcy tologyfro mtheASC-US
catego ry .Fo rthi sandot herreason s,theobserve d3%
ation beca useofi tsa ss ociationwi thce rvi caladen ocar
-cin omas ,which are le ssefficien tlyd ete ctedbyc ytolo gythansquamousca ncers.
Figure 3.
5-year risk of CIN 3+ after ASC-US among women aged

30 years and older in the KPNC cohort was lower than
the 2-year risk seen in ALTS. In fact, risk was low enough
to justify annual rather than semiannual cytology as
sufficiently sensitive to identify women with CIN 3+ (61).
Recent 2011 screening guidelines recommended that
womenw ithH PV-negati veASC-USco -testingres ultsbe
manage dwit hroutinef ollow-up(1 0).Thiswasb asedon
anearl iera nalysisof asmallerKP NCdataset.A nalysis
ofanex pand eddataset foundthatw hiletheabso lute
riskof CIN3 +waslowaf terHPV-neg ativeASC-US ,it
wasmor ecom parableto CIN3+riska mongwomen
withne gati vecytolog yalonethan thosewithan egative
co-tes t(26 ),suggest inga3-year intervalfor follow-up.
Inaddi tion ,womenove r60yearsof agewithHPVnegati veAS C-UShadah igherriskf orcervicalc ancer
during foll ow-upthan womenwithn egativeco-t esting,
sugges ting thattheyn eedcontinu edscreening .
Triage using HPV genotyping was considered. Women

withAS C-USw hoa lsohadHPV- 16o rHPV-18dete cted
hadapp roxim ate lytwicethe ris kofCIN3+asw omen
withAS C-USa ndh igh-riskHP Vty pesothertha n16or
18 (61Y63). Nevertheless, KPNC data showed that the
risk for CIN 3+ in both groups exceeded the threshold
for colposcopy (26). HPV-16/18 genotyping of HPVpositive women with ASC-US did not appear to lead to
different management.
Figure 4.
&
S9
No new information that would change the 2006

gu ide lineswaside ntif iedon ASC-US inp regnantor
po stm enopausalwo men.
Management of Women with ASC-US (Fig. 4)
For women with ASC-US cytology, reflex HPV testing is
pre ferre d(BI ).Forw omenwithH PV-neg ati veASC-U S,
whe therf romr eflexH PVtesting orco-t est ing,rep eat
co- testi ngat 3years isrecomme nded(B II) .Forwom en
wit hHPV- posi tiveAS C-US,whet herfro mre flexHPV
tes tingo rco- testin g,colposc opyisr eco mmended (BI).
Whe ncolp osco pydoes notidenti fyCINi nwo men
wit hHPV- posi tiveAS C-US,co-t esting at1 2months is
rec ommen ded( BII).I ftheco-te stisHP Vne gativea nd
cyt ology nega tive,r eturnfora ge-app rop riatete stingin
3ye arsis reco mmende d(BII).If alltes tsa renegat iveat
tha ttime ,rou tinesc reeningis recomm end ed(BIII ).It
isr ecomm ende dthatH PVtesting infoll ow- upafter
col posco pyno tbeper formedati nterva lso flessth an
12m onths (EII I).
For women with ASC-US cytology and no HPV resul t,rep eatc ytolog yat1year isa cc ept able(BII) .Ifthe
res ultis ASC- USorwo rse,colp osc op yis recommend e
d; ifthe resu ltisne gative,r etu rn toc ytologyte stinga t
3-y earin terv alsisr ecommend ed( BI I).
Endocervical sampling is preferred for women in
whom no lesions are identified (BII) and for those with an
S10
&
MASSAD ET AL.
Figure 5.
inadequate colposcopy (AII) but is acceptable for women

with an adequate colposcopy and a lesion identified in the
transformation zone (CII).
Because of the potential for overtreatment, the routineuse of dia gnosticex cis ionalprocedure ssu chasloop
electro su rgi calexcisi onf orwomenwithani nit ialASCUSinthe ab sen ceofCIN2+ isu nacceptable(EI I).
ASC-US in Special Populations

Women Aged 2124
Y years (Fig. 5)
Initial Management
For women aged 2124
Y years with ASC-US, cytology
alone at 12-month intervals is preferred, but reflex HPV
testing is acceptable (BII). If reflex HPV testing is
performed with ASC-US and the HPV result is positive,
repeat cytology in 12 months is recommended (BII).
Immediate colposcopy or repeat HPV testing is not
recommended. If reflex HPV testing is performed and is
negative, return for routine screening with cytology
alone in 3 years is recommended (BII).
Follow-Up
worse at the 24-month follow-up, colposcopy is recommended. For women with two consecutive negative results, return to routine screening is recommended. (BII)
Women Aged 65 Years and Older. Postmenopausal

women with ASC-US should be managed in the same
manner as women in the general population, except
when considering exit from screening for women aged
65 years and older. For those women, HPV-negative
ASC-US results should be considered abnormal (AII).
Additional surveillance is recommended with repeat
screening in 1 year; co-testing is preferred but cytology is
acceptable (BII).
Pregnant Women. Management options for pregnant

women with ASC-US are identical to those described
for nonpregnant women, with the exception that deferrin gcolposcopy until6 week spo stpartumi sacc eptable
(CI II).Endocer vicalc uret tag einpregna ntwo menis
una cceptable(E III).F orpr egn antwomenw hoha veno
cyt ologic,hist ologic ,orc olp oscopical lysu spectedCIN
2+a ttheinitial colpos copy ,po stpartumf ollo w-upis
rec ommended(BI II).
For women with ASC-US who are aged 21Y24 years,

follow-up with cytology at 12-month intervals is recommended. Colposcopy is not recommended. (BII) For
women with ASC-H or HSIL+ (HSIL, atypical glandular
Postmenopausal women with
Postmenopausal
Women
.
cells [AGC], or cancer) at the 12-month follow up, colASC-USshouldbe manag edinthesamemanneras
poscopy is recommended. For women with ASC-US or women in the general population (BII).
&
S11
Figure 6.
Low-Grade Squamous Intraepithelial Lesion

The ASCUS-LSIL Triage Study showed that the natural
history of LSIL approximates that of HPV-positive ASCUS (64), suggesting that women with either should be
managed similarly. Analysis of the KPNC dataset confirmed that women with LSIL at ages 21Y24 years carry
a lower risk of CIN 3+ than older women (33, 65). Lowgrade squamous intraepithelial lesions are highly associated with HPV infection, with a pooled estimate of
HPV positivity of 77% (66). This rate appears too
high to allow reflex HPV testing to select women for
colposcopy efficiently. However, when co-testing is performed in women 30 years of age and older, some women
have HPV-negative LSIL. In the KPNC cohort, the risk
of CIN 3+ in HPV-negative women with LSIL was low,
similar to that of ASC-US alone (67).
co-testing after an additional 3 years is recommended.

If all tests are negative at that time, routine screening is
recommended (BIII).
LSIL in Special Populations
Women Aged 2124
Y Years (Fig. 5). For women with
LSIL who are aged 21-24 years, follow-up with cytology
at 12-month intervals is recommended (BII). Colposcopy isnotrec ommended( DI I).Forwomen withAS C-H
or HSIL+att he12-mont hf ollowup,col poscop yis
re commende d.Forwome nw ithASC-USor worsea tthe
24 -monthfo llowup,co lp oscopyisrec ommend ed.For
wo menwitht woconsecu ti venegativer esults ,returnto
ro utinescr eeningisr ec ommended(BI I).
For pregnant women with

Pre gnantWom en(Fi g.7).
LSI L,colpos copyi spreferred(BI I).En docer vicalcure tFor women with LSIL cytology and no HPV test or a tage in pregnant women is unacceptable (EIII). For
pos itive HPVt est, colposco pyi sr eco mmen de d(AI).I pregnant women aged 2124
Y years, follow-up according
fco to the guidelines for management of LSIL in women
tes tings hows HPV- negative LSI L, rep eatc o- testingat 1ye arisp referred,b ut colposcopyi sacce pt able.Ifrepe at
aged 21Y24 years is recommended (discussed in previous
co-testing at 1 year is elected, and if the cytology is ASC- paragraph). Deferring colposcopy until 6 weeks postparUS or worse or the HPV test is positive (ie, if the co-testing tum is acceptable (CIII). For pregnant women who have
result is other than HPV negative, cytology negative), no cytologic, histologic, or colposcopically suspected CIN
colposcopy is recommended. If the co-testing result 2+ at the initial colposcopy, postpartum follow-up is
at 1 year is HPV negative and cytology negative, repeat recommended (BIII). Additional colposcopic and cytologic
Management of Women with LSIL (Fig. 6)
S12
&
MASSAD ET AL.
Figure 7.
examinations during pregnancyare unacceptable for these

women (DIII).
Postmenopausal Women. Acceptable options for the
management of postmenopausal women with LSIL and
no HPV test include obtaining HPV testing, repeat cytolo gic test ingat6m onthsand1 2mo nths,and colpos copy
(C III ).If theHPVt estisnega tiv eorifCIN isnoti denti fie datc olposco py,repeat cyt ologyin1 2month sis
Figure 8.
recommended. If either the HPV test is positive or repeat

cytology is ASC-US or greater, colposcopy is recomm e n d e d ( A I I ) . I f t w o c o n s e c u t i v e repeat cytology tests are
negative, return to routine screening is recommended. (BII)
Atypical Squamous Cells, Cannot Exclude High-Grade
Squamous Intraepithelial Lesion (ASC-H)
Data from KPNC confirmed that a report of ASC-H
confers higher risk for CIN 3+ over time than ASC-US or
&
S13
Figure 9.
LSIL (68, 69), although risk is lower than that following

HSIL. This is also true for women aged 21Y24 years,
although their risk of CIN 3+ is lower than that for older
women with ASC-H (33). The high rate of HPV detection in women with ASC-H makes reflex HPV testing
unsuitable (3). In addition, the 5-year cancer risk among
women with HPV-negative ASC-H is 2%, which is too
high to justify observation (68).
Management of Women With ASC-H (Fig. 8). For
women with ASC-H cytology, colposcopy is recommended
regardless of HPV result. Reflex HPV testing is not
recommended (DII).
ASC-H in Special Populations
Women Aged 2124
Y Years (Fig. 9)
Colposcopy is recommended (AII). Further management
should follow guidelines for women aged 2124
Y years
with HSIL.
High-Grade Squamous Intraepithelial Lesion (HSIL)
HSIL cytology results identify women at substantial risk.
CIN 2+ is found at colposcopy in some 60% of women
with HSIL (69Y71). This justifies immediate excision of
the transformation zone for many women, especially
those who are at risk for loss to follow-up or who have
completed childbearing. Cervical cancer is found at
colposcopy in some 2% of women with HSIL, although

risk rises with age and is low among women aged 21Y24
years, even with follow-up (33). Five-year cervical cancer risk is 8% among women 30 years of age and older
(72). Risks are modified by HPV test results: HPVnegative HSIL co-test results, although uncommon, still
carry a 5-year risk for CIN 3+ of 29%, while 7% will
develop cancer (72). This precludes reflex HPV triage
for HSIL. In the KPNC cohort, among women 30 years
of age and older with HPV-positive HSIL, the 5-year risk
of CIN 3+ was 50%, while the 5-year cancer risk was
7% (72). When HPV results are known from co-testing
for women with HSIL, these risks may inform the choice
between immediate diagnostic excision and colposcopy
and between diagnostic excision and cytologic and colposcopic surveillance when CIN 2+ is not identified. The
sensitivity of colposcopy for detecting CIN 2+ is lower
than previously appreciated (73Y75), and multiple biopsies should be considered at colposcopy when large
confluent or multiple discrete lesions are seen.
Management of Women With HSIL (Fig. 10). For
women with HSIL cytology, immediate loop electrosurgical excision or colposcopy is acceptable, except in
special populations (BII). Triage using either a program
of repeat cytology alone or reflex HPV testing is unacceptable (EII). For women not managed with immediate
excision, colposcopy is recommended regardless of HPV
S14
&
MASSAD ET AL.
Figure 10.
result obtained at co-testing (BII). Accordingly, reflex

HPV testing is not recommended (BII).
A diagnostic excisional procedure is recommended for
w omenwithHS ILwhenthec olposcopi ce xaminationi s
i nadequate, exceptduri ngpregnan cy (BII).Women with
C IN2,CIN3,a ndCIN2,3sh ouldbeman ag edaccording
t otheapprop riate2012c onsensusg ui deline(see Mana gementofWo menWithCIN 2,CIN3,an dC IN2,3).
A blationisu nacceptabl einthefol lo wingcircums tances:
w hencolposc opyhasnotb eenperfor me d,whenCIN2, 3
i snotidenti fiedhistol ogically, an dwhentheend ocervical
a ssessmenti dentifiesC IN2,CIN3, CI N2,3orungra ded
C IN(EII).
2, CIN 3, and CIN 2,3). (BIII) If during follow-up a highgrade colposcopic lesion is identified or HSIL cytology
persists for 1 year, biopsy is recommended. (BIII) If HSIL
persists for 24 months without identification of CIN 2+, a
diagnostic excisional procedure is recommended. (BIII) A
diagnostic excisional procedure is recommended for
women aged 21Y24 years with HSIL when colposcopy is
unsatisfactory or CIN 2, CIN 3, CIN 2,3, or ungraded
CIN is identified on endocervical sampling. (BII) After
two consecutive negative cytology results and no evidence
of high-grade colposcopic abnormality, return to routine
screening is recommended (BIII).
HSIL in Special Populations
Atypical Glandular Cells, Cytologic Adenocarcinoma

In Situ, and Benign Glandular Changes
Women Aged 2124

Y Years (Fig. 9). For women aged
2124
Y years with HSIL, colposcopy is recommended.
Immediate treatment (ie, see-and-treat) is unacceptable.
(AII) When CIN 2+ is not identified histologically, observation for up to 24 months using both colposcopy and
cytology at 6-month intervals is recommended, provided
the colposcopic examination is adequate and endocervical assessment is negative or CIN 1 (BIII). If CIN 2, CIN 3,
or CIN 2,3 is identified histologically, management
according to the 2012 consensus guideline for the management of young women with CIN 2, CIN 3, or CIN 2,3
is recommended (see Management of Women With CIN
An AGC interpretation is poorly reproducible (76) and

un com mon(77).AGChas be enasso ciatedwithpo lyps
an dme taplasiabutals ow ithneo plasias,incl udin gaden oca rcinomasofthee nd ometri um,cervix,ov ary, fallo pia ntube,andother si tes(78 ).Neoplasiar iski shigher
wh enr eportedasAGCfa vo rneopl asiaorfrankA IS.
Al tho ughthecancerri sk islowe rinwomenyoun ger
th an3 5yearsofagewit hA GC,the riskofCIN2+i s
hi ghe r,andintensive as sessme ntiswarrante data ll
ag es( 78).IntheKPNCc oh ort,CI N3+wasfoundi n
9% ofw omenaged30year sa ndolde rwithAGC
cy tol ogy,withcancer in 3%(72, 77).Despitei ts
&
S15
Figure 11.
appellation, AGC cytology is most commonly associated with squamous lesions including CIN 1. However,
glandular and squamous lesions often coexist, with
CIN found in approximately half of women with AIS
(79Y81), so identification of CIN does not preclude AIS
or adenocarcinoma. Although cervical adenocarcinoma is HPV associated and can be detected with HPV
testing, endometrial cancer is not, so reflex HPV testing
does not identify a subgroup of women who need less
invasive assessment. A negative HPV test can be useful
in identifying women at greater risk for endometrial
rather than cervical disease (80). Endometrial cancer
risk is low in young women without endometrial cancer
risk factors but is substantially greater in older women
and young women with risk factors.
Benign-appearing endometrial cells and stromal cells
orhistiocytesare rarelyassoc iated wit hpremal ignant
lesionsorcanceri nyoungwomen .Howe ver ,inpost menopausalwomen, thesechange scanb eas sociate d
withanapproximat ely5%riskof clini cal lyimpor tant
pathologyincludi ngendometri alade noc arcinom a(81).
Management of Women With AGC or Cytologic AIS

Initial Workup (Fig. 11)
Forwome nwitha llsub categor iesof AGCa ndA ISexceptaty picale ndome trialce lls,c olpo sco pywithendocervica lsampl ingis recomme ndedr egar dle ssofHPV
result( AII).A ccord ingly,t riage byre fle xHPVtesting
is not recommended, and triage using repeat cervical

cytology is unacceptable (DII). Endometrial sampling is
recommended in conjunction with colposcopy and endocervical sampling in women 35 years of age and older
with all subcategories of AGC and AIS (BII). Endometrial sampling is also recommended for women younger
than 35 years with clinical indications suggesting they
may be at risk for endometrial neoplasia (BII). These
include unexplained vaginal bleeding or conditions suggesting chronic anovulation. For women with atypical
endometrial cells, initial evaluation limited to endometrial and endocervical sampling is preferred, with colposcopy acceptable either at the initial evaluation or
deferred until the results of endometrial and endocervical
sampling are known; if colposcopy is deferred and no
endometrial pathology is identified, colposcopy is then
recommended (AII).
Subsequent Management (Fig. 12)
For women with AGC not otherwise specified cytology in whom CIN 2+ is not identified, co-testing at
12 months and 24 months is recommended. If both cotests are negative, return for repeat co-testing in 3 years
is recommended. If any test is abnormal, colposcopy is
recommended. (BII)
If CIN 2+ but no glandular neoplasia is identified histo log ic all yd uringthei nitialwor ku pofawomanw ith
at ypi ca len do cervical, endometri al ,orglandul arcellsnot
S16
&
MASSAD ET AL.
Figure 12.
otherwise specified, management should be according to tients with a cytologic report of benign glandular cells,
the 2012 consensus guidelines for the lesion found (CII). no further evaluation is recommended (BII).
For women with AGC favor neoplasia or endocer vical AISc yto logy,if invasivedis ea seisnotidentif ie
d
MANAGEMENT OF CIN AND HISTOLOGIC AIS
dur ingth eini tia lcolpos copicworkup ,a diagnosticex- cis ionalproc ed ureisrec ommende d( AII ).
CIN 1 and No CIN Found at Colposcopy After
It is recommended that the type of diagnostic exciAbnormal Cytology
si on alprocedure used int hiss et tingprovid eanintact
sp ec imenwithint erpr eta blem ar gins(BII). Endocervi CIN 1 is the histologic manifestation of HPV infection.
ca l samplingaft erex cis ioni sp referred(B II).
Alt h ou ghm ostCIN1les ionsareassoci at edw ithoncogen i cH PV, HPV-16isle sscommoninCIN 1t han in
CIN 3 ,a ndn ononcogeni cHPVtypesarea ls oco mmonly
fou n di nCI N1lesions( 82,83).Thenat ur alh istoryof
AGC or Cytologic AIS in Special Populations
CIN 1 is sim ilartothat ofHPV-positiv eA SC- USandLSIL
int h ea bse nceofCIN,s uggestingsimi la rma nagement.
Pregnant Women
Reg r es sio nratesareh igh,especiall yi nyo ungerwomen
Theiniti alevaluat ionofAG Cinpregnan tw ome n
(32 , 64 ),a ndprogress iontoCIN2+isu nc omm on(64,84).
shouldbe identical tothato fnonpregna nt wom en
The r is kof occultCIN3 +amongwomenwi th CIN 1at
(BII),
col psyareunacce
p os cop icbiopsyis
linkedtotheri
sk con veyedbyprior
exceptth atendocer vicalcu rettageand en dom et rialbio
pt able(EIII
).
cyt o lo gy. KPNCdatash owedsimilar,r el ati velylow5-yea
r r i sk ofC IN3+whenCI N1ornolesionw as dia gnosed
aft e rA SC- USorLSIL,b utasubstantia ll yhi gherriskafter
HSI L ,A SC- H,andAGC.F orexample,wom en wit hCIN
Women Aged 2124
Y Years
It is recommended that ASCCP guidelines for manage- 1af t er LSI LorHPV-pos itiveASC-USha da 5-y earrisk
me nt ofAGCbefoll owed foral lwomen,inc lud ingthose ofC I N3 +of 3.8%,while thosewithCIN1 af ter HSIL
had a 5- yea rriskofCIN 3+of15%(68).
ag ed 2124years(B II).
Y
For asympMan agementofBenignGl an dularC hanges.
tom aticpremenopausal wo menwit hbenignen dometrial
cells, endometrial stromal cells, or histiocytes, no further
evalua tionisrecom mended( BII).F or postmenopaus al
womenw ithbenignen dometri alcell s, endometriala ssessme ntisrecomme nded(BI I).For po sthysterecto my pa-
Failure to detect CIN 2+ at colposcopy in women

withHSI Ld oesnot mea nt ha taCIN2+les io nhasbeen
exclude d, althou gho cc ul tcarcinoma is unlikely.A s
a
result, wo menwit hHS IL wh odonothave im mediatedi agno stic
&
S17
of the natural history of HSIL managed without treat- lesion seen cannot be graded, as an associated invasive
ment have been reported, and follow-up in those is cancer cannot be excluded without a diagnostic excilimited (68); management relies on expert opinion.
sion procedure.
Women with minor cytologic abnormalities have
simil arri skfor CIN3+whet hercolposcopy showsCIN Management of Women With CIN 1 or No Lesion
1orno lesi on(64 ,68).Sinc eCIN3+riskise levatedfor
Preceded by Lesser Abnormalities (Fig. 13). Co-testing
women with eithe rHPV-16or HPV-18orpersi stent
oncog enic HPVin fectionof anytypeevenwh encytol- at 1 year is recommended (BII). If both the HPV
ogyis nega tive, guideline smustprovidef orfollow-up test and cytology are negative, then age-appropriate
forwo menw ithth eseless erabnormaliti esevenwhe retesting 3 years later is recommended (cytology if age
n
is younger than 30 years, co-testing if 30 years of age
noCIN isfo und.T heseles serabnormalit iesinclude
older).
all tests
are negative,
HPV-1 6orH PV-18 positivit y,persistentu ntypedonco-orgeni
cHPIfV,A
SC -US,and
LSIL. then return to routine
screening is recommended (BII). If any test is abnormal,
then colposcopy is recommended (CIII).
The management of CIN 1 in endocervical samples
If CIN 1 persists for at least 2 years, either continued
mer itsspecial at ten t io n.Traditiona lmanagementstr at fo llo w -uportre atm en tisac c eptabl e(CII) .Iftreate- giesprescr ib ede x ci sionaltherap yforwomenwith
me nti s selected and th ecolp o scopic examin ationis
CIN onendocerv ic als a mp ling.However ,thesestrateg ad equ a te,eithe rex ci siono r ablati onisac ceptable
ies
(A I). A diagnost ice xc ision a lproce dureis recompre cededfullu nd ers t an dingofthehig hspontaneous
me nde d ifthecol pos co picex a minati onisin adequate;
reg ressionrat es ofC I N1 .Endocervica lsamplesare
th een d ocervica lsa mp lingc o ntains CIN2,C IN3,CIN
oft encontamin at edb y ec tocervicalle sions.Womenwi 2, 3or u ngradedC IN; or thepa t ientha sbeenp reviously
th CIN1onendo ce rvi c al samplinghave alowriskfor
tr eat e d(AIII). Tre at mentm o dality should bedeterCIN 2+(85,86)( Fu kuc h iE ,FettermanB, PoitrasN,
mi ned b ythejudg men to fthec l inicia nandsh ouldbe
Kin neyW,Lorey T, Lit t le RD.Riskofcer vicalprecan- gu ide d byexperi enc e, resou r ces,an dclini calvaluefor
cer andcanceri nw ome n wi thcervicalin traepithelial
th esp e cificpat ien t( A1II) . Inpati entswi thCIN1and
neo plasiagrad e1 one n do cervicalcure ttage.JLowGen an ina d equateco lpo sc opice x aminat ion,ab lativeproce
it
Tra ctDis[inpr es s]) . Cu rrentguideli nesonmanagemen tdu
ofCIN
vicalsampli
ngdonotapp
CIN2, CIN3,orCIN
res a1onendocer
reunacce pta
bl e(EI) . Podoph
yllinolywhen
rpodophyllinrelat ed pro
Figure 13.
S18
&
MASSAD ET AL.
Figure 14.
or on the cervix (EII). Hysterectomy as the primary and

principal treatment for histologically diagnosed CIN 1 is
unacceptable (EII).
that the colposcopic examination is adequate and the

endocervical sampling is negative. (BIII). In this circums t a n c e , i t i s a c c e p t a b l e t o r e v i e w the cytologic, histologic,
and colposcopic findings; if the review yields a revised
Management of Women With CIN 1 or No Lesion interpretation, managementshould follow guidelines for
Preceded by ASC-H or HSIL (Fig. 14). When CIN 2+ the revised interpretation (BII). If observation with coi s n o t i d e n t i f i e d h i s t o l o g i c a l l y , either a diagnostic excisional testing is elected and both co-tests are negative, return for
procedure or observation with co-testing at 12 months and retesting in 3 years is recommended. If any test is abnor24 months is recommended, provided in the latter case mal, repeat colposcopy is recommended. A diagnostic
Figure 15.
excisional procedure is recommended for women with

repeat HSIL cytologic results at either the 1-year or 2-year
visit (CIII).
&
S19
Follow-up with HPV testing is unacceptable (EII). For

women with ASC-H or HSIL+ at the 12-month follow
up, colposcopy is recommended. For women with ASCUS or worse at the 24 month follow up, colposcopy is
Management of Women With CIN 1 on Endocervical recommended. After two consecutive negative tests,
routine screening is recommended. (BII)
Sampling. When CIN 1 is detected on endocervical
samp lin g af terlesse ra bnormalitiesbutnoCIN2 +is
For women aged 21Y24 years with CIN 1 after ASC-H
dete cte d in colposco pi cbiopsies,managements houl or HSIL cytology, observation for up to 24 months using
d
foll owA S CC Pmanagem en tguidelinesforCIN1,wi t both colposcopy and cytology at 6-month intervals is
recommended, provided the colposcopic examination is
hth ead d it ionofrep ea tendocervicalsampling in12
mont hs( B II ).Forwom en withCIN1onendocervica l adequate and endocervical assessment is negative (BIII). If
samp lin g an dcytolog yr eportedasASC-H,HSIL,o r CIN 2, CIN 3, or CIN 2,3 is identified histologically,
AGC, orw i th acolposc op icbiopsyreportedasCIN 2+,
management should follow the guideline for the manmana gem e nt accordin gt otheASCCPmanagement
guid eli n es forthesp ec ificabnormalityisreco mmend agement of young women with CIN 2, CIN 3, or CIN 2,3
ed
(BIII, see Management of Women With CIN 2, CIN 3,
(BII ).F o rw omennott re ated,repeatendocervic alsam pling
atthetimeofev
at ionfollow-up
fo rtheotherab
no rmalityisr ecommend
and CIN
2,3). Ifalu
during
a high-grade
colposcopic lesion is identified or HSIL cytology persists
for 1 year, biopsy is recommended (BIII). If HSIL persists
for 24 months without identification of CIN 2+, a diagnostic excisional procedure is recommended (BIII). When
CIN 1 in Special Populations
colposcopy is inadequate or CIN 2, CIN 3, CIN 2,3 or
ungraded CIN is identifiedon endocervical sampling,
Women Aged 2124
Y Years (Fig. 15). For women aged adaignoscti excsionprocedure is recommended (BII).
2124
Regardless of antecedent cytology, treatment of CIN 1
Y years with CIN 1 after ASC-US or LSIL cytology,
repeat cytology at 12-month intervals is recommended. in women aged 21Y24 years is not recommended (BII).
Figure 16.
S20
&
MASSAD ET AL.
Pregnant Women. For pregnant women with a histo- does not pose a risk to the pregnancy and poses no imlog icdiagno sisof CIN1 , follow-upwit houttreat me nt mediate risk to the mother. Treatment during pregnancy
isr ecommend ed(BI I).T r eatmentofpre gnantwome n
carries substantial risk for hemorrhage and pregnancy loss.
for CIN1isun accep tabl e .
Management of Women With CIN 2, CIN 3,
and CIN 2,3 (Fig. 16)
CIN 2, CIN 3, and CIN 2,3
Initial Management. For women with a histologic diWhile distinction between CIN 2 and CIN 3 is difficult
agnosis of CIN 2, CIN 3, or CIN 2,3 and adequate
inind ividualcase s,regre ssi o nra tes a re lowerandprogress iontocancer morecom mon f orw ome n wi thCIN3 colposcopy, both excision and ablation are acceptable
thanf orthosewith CIN2(87 ,88 ) .Ce rvi c al intraepithel ial treatmentmo dali ties,exc ept inpregna ntw omenand
neopl asia2remain sthecon sen s ust hre s ho ldfortreatme n youngwomen( AI). Adiagnos tic excision alp rocedure
tint heUnitedSta tes,exc ept i nsp eci a lc ircumstances .
isrecommend edfo rwomenwi thr ecurrent CIN 2,CIN
Women withunambig uousCIN 3ha v eth eim m ed iate
3,orCIN2,3( AII) .Ablatio nis unaccept abl eandadiprecu rsortoinvas ivecanc era n dsh oul d no tbeobserved, agnosticexc isio nalproce dur eisrecom men dedfor
regar dlessofageo rconcer nab o utf utu r ef ertility.
womenwithah isto logicdia gno sisofCIN 2,C IN3,or
CIN2,3andin adeq uatecolp osc opyorend oce rvical
samplingsho wing CIN2,CIN 3,C IN2,3,or CIN not
After treatment for CIN 2+, recurrence risk remains graded(AII) .Obs ervation ofC IN2,CIN3 ,or CIN2,3
withsequent ialc ytologya ndc olposcop yis unacceptwella bovethato fwo men wit hnegativec o-te stresults
throu ghoutobse rva tio npe riodsthath aveb eenreported able,except inpr egnantwo men andyoung wom en(EII).
Hysterectom yisu naccepta ble asprimar yth erapyfor
todat e(89).Aft ert won ega tiveco-tes tsin thefirst
CIN2,CIN3,o rCIN 2,3(EII) .
2year saftertre atm ent ,ri skissimila rtot hatofwomen
witha negativeP apt est ,su ggestinga3 -yea rinterval
betwe ensurveil lan cee xam inations(8 9).W hetherroutines creeningm ayb eap pro priateafte rthr eeormore
negat iveco-tes tsi sun cle ar.
The objective of screening during pregnancy is to identify cervical cancer. Cervical intraepithelial neoplasia 3
Figure 17.
For women treated for

Fol low-U pAfterT reatment.
CIN 2,CIN 3,orCIN 2,3,co-testin gat12 monthsand
24 months is recommended (BII). If both co-tests are
negative, retesting in 3 years is recommended (BII). If

any test is abnormal, colposcopy with endocervical
sampling is recommended (BII). If all tests are negative,
routine screening is recommended for at least 20 years,
even if this extends screening beyond 65 years of age
(CIII). Repeat treatment or hysterectomy based on a
positive HPV test is unacceptable (EII).
If CIN 2, CIN 3, or CIN 2,3 is identified at the margi nso fa dia gn os tic exc is ionalproce du reo rinanendo
ce rvi ca lsa mp le obt ain ed immediatel ya fte rtheproce
4Y6monthsaftertreatmentispreferred (BII). Performing a
repeat diagnostic excisional procedure is acceptable (CIII).
H y s t e r e c t o m y i s a c c e p t a b l e i f a repeat diagnostic procedure is not feasible (CIII).
A repeat diagnostic excisional procedure or hysterect omyisa cceptablef orwomenwit hahistolo gi cdiagnosis
o frecur rentorpers istentCIN2 ,CIN3,orC IN 2,3(BII).
CIN 2, CIN 3, or CIN 2,3 in Special Populations
&
S21
with a histologic diagnosis of CIN 2, CIN 3, or CIN 2,3

at intervals no more frequent than every 12 weeks (BII).
Repeat biopsy is recommended only if the appearance of
the lesion worsens or if cytology suggests invasive cancer (BII). Deferring reevaluation until at least 6 weeks
postpartum is acceptable (BII). A diagnostic excisional
procedure is recommended only if invasion is suspected
(BII). Unless invasive cancer is identified, treatment
is unacceptable (EII). Reevaluation with cytology and
colposcopy is recommended no sooner than 6 weeks
du r e,reasses smentusing cytologyw it he nd ocervicalsampl ingat
postpartum (CIII).
ADENOCARCINOMA IN SITU (AIS)

The incidence of AIS is low but rising (90). Management
ofA ISiscontr ov ers ia l,a sma nyassu mptio nsusedto
jus tifyconse rv ati ve man age mentfo rwome nwithCIN2
and CIN3donot ap ply .F ore xam ple,co lposc opicchanges
ass ociatedwi th AIS ca nbe min imal,s odete rminingthe
lim itsofales io nca nb edi ffi cult.A ISfre quentlyextend s
int otheendoc er vic al can al, compli catin gdeterminatio n
ofthedesire dd ept ho fex cis ion.AI Scanb emultifocalan d
dis continuou s, son eg ati vem argins onane xcisionspecimen donotprov id eas su ran cet hatthe disea sehasbeen
com pletelyex ci sed .I nva siv ecance rcann otbeexcluded
wit houtadiag no sti ce xci sio nalpro cedur e.
Young Women (Fig. 17). For young women with a histologic diagnosis of CIN 2,3 not otherwise specified,
either treatment or observation for up to 12 months
usingb othcolpos co pyandcytolo gya t6 -m on thinterval sisaccept ab le,provided col po sc op yisadequat
e.
For these reasons, total hysterectomy remains the
(BIII) Whenahist ol ogicdiagnos iso fC IN 2i sspecifie
tre atmen tofchoic einwo menwhohaveco mpleted
d
chi ldbea ring.For women whowishtomai ntainfe rtilit
forayo ungwoman, ob servationis pre fe rr ed buttreat
y,
obs ervat ionisano ption ,althoughitc arriesa lessthan10%r is kofpe
mentis acceptabl e. Ifthecolpos cop ic ap pe aranceofthe lesi onworsenso rif HSILcyto lo gyorahi gh-gradeco lp oscopiclesi
when excision margins are negative (91Y3). Like margin
After two consecutive negative cytology results, an ad- status, endocervical sampling at the time of an excisional
ditio nal co-test1yea rlateris recommen ded(BIII ). Ifthe
procedure also predicts residual disease (94). Moreover,
addit ion alco-testis negative ,thenrep eatco-te st ingin
a negative HPV test after treatment identifies women at
3year sis recommended (BIII).C olposcop yisrecom me nde
low risk for persistent or recurrent AIS (94). In 2001,
dife ith erthe2-year or5-year co-testi sabnorma l( BIII).
knife conization was favored over loop excision because
Treatment is recommended if colposcopy is inade- margin status and the interpretability of margins are
quate, if CIN 3 is specified, or if CIN 2 or CIN 2,3 critical to future treatment planning. In 2006, wording
persists for 24 months (BII). For women aged 21Y24 was changed to allow diagnostic excision using any moyears who are treated, follow-up according to ASCCP dality, but care must be taken to keep the specimen intact
guidelines for treated CIN 2, CIN 3, or CIN 2,3 is and margins interpretable, avoiding fragmentation of the
specimen, including top-hat serial endocervical excirecommended (BIII).
Treatment is recommended if CIN 3 is subsequently sions. This may require use of larger loops than those
identifie do rifCIN2,CIN 3, orC I N2 ,3persistsfor
employed to excise visible squamous lesions.
24months( BI I).
Management of Women With AIS (Fig. 18)
In the absence of invasive disease or Hysterectomy is preferred for women who have comPr egn antWome n.
pletedchildb ea ringandha vea histo log icdi agnosisofA
ad van cedpreg na ncy,addi tionalc olposcopica ndcyto- ISonaspecim en fromadiag nos ticex cis iona lprocedure
logic examinations are acceptable in pregnant women
S22
&
MASSAD ET AL.
Figure 18.
(BIII). Conservative management is acceptable if future

fertility is desired (AII). If conservative management is
planned and the margins of the specimen are involved or
endocervical sampling obtained at the time of excision
contains CIN or AIS, reexcision to increase the likelihood
of complete excision is preferred. Reevaluation at 6
months using a combination of co-testing and colposcopy
with endocervical sampling is acceptable in this circumstance. Long-term follow-up is recommended for
women who do not undergo hysterectomy (CIII).
The effect of HPV vaccination on large cohorts over

long periods of follow-up remains to be studied, and
whether prior HPV vaccination alters natural history or
management of cytologic or histologic abnormalities
remains unknown. Prospective study of the negative
consequences of screening, diagnosis, and treatment are
needed to allow balancing of risks and benefits.
Outcomes analyses using the LAST Projects two-tier
squamous intraepi theli all esio ns(SIL)te rminologyare
neededto directho wtran sla tion ofthree-t ierCINterminology tothetwo -tier ter mino logycanbe madeand
todefine howspeci ficma nag emen trecommen dations
forhisto logicdia gnose sin thet wo-tiersy stemcanbe
RECOMMENDATIONS FOR FUTURE RESEARCH
created( SeeBox2) .Inpa rti cula r,studies ofthesafety
ofobserv ationfor young wom enwi thhistolo gicHSIL
Literature review for the 2012 ASCCP Consensus Guideareneede d,asrepo rtsto dat ehav eincluded diagnostic
lines Conference identified several issues important to excision asastudy endpo int .Est imatesofr egression
patient management that lack high-level evidence.
andprogr essionra tesan dth epro portionof women
Follow-up is insufficient to determine posttreatment whoevent uallyreq uiree xci sion areneeded .Long-term
outcomes afterapp arent reg ress ionwithou ttreatment
outcomeso ro ptimallong-t er mfollow-u pintervals
areunkno wn.
forwomenw it htreatedCIN2 an dCIN3mana ged
withseria lc o-testing.Ev id encetogui demanagement
ofwomenwi th negativecolp os copyafter abnormal
cytologyo rw ithCIN1isals os canty.The pathto
routinesc re eningforthes ew omenisbas edonconsensus
As the number and sophistication of tools applied
expertopi ni onandshouldb em odifiedas evidencebeto cer vicalc anc erpreventionco nt inuet oincrease, the
comesavai la ble.
co mpl exityo fma nagementpromis es togro w.Electro
ni c
me dic alreco rds andbedsideandp oc ketco mputersho
Follow-up studies of women managed using HPV ld
genotypin g,p16an do theri mmunost ains, cytogenetic gr eat promis efo rassistingclin ic iansa ndpatients inne
s,andoth ermarke rs arene ededtog uidet heirincor- got iating thi scomplexity.De ve lopme ntofrisksc oringth atinco
porationi ntomana ge mento fcervic alabn ormalities.
benefits on a more individualized level than consensus

guidelines. Future consensus conferences will be needed
to integrate new approaches.
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S23
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30. Khalid S, Dimitriou E, Conroy R, Paraskevaidis E, logic cytology. Arch Pathol Lab Med. 2009;133:1912Y6.
Kyr giouM, Ha rrityC,et al .Theth ic knessandvolum eof
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LLE TZspec im enscanpre di ctther el ativeriskofpr egnancy- cyt olog yon conventi on alandliquid -ba sedpreparations:Acom pre hens ive reviewof si milaritiesa ndd ifferences.DiagnCyto pa t
related morbidity. BJOG 2012;119;685Y91.
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for high- gr adece rv ica ld ysplasi a. AustN ZJOb stetGynaec
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66. Arbyn M, Sasieni P, Meijer CJ, Clavel C, Koliopoulos
54. Elumir-Tanner L, Doraty M. Management of Papa- G, Dillner J. Chapter 9: clinical applications of HPV testing : a
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55. Zhao C, Austin RM. Human papillomavirus DNA Poi trasN E,L oreyT,eta l. Five-Y ear RisksofCI N2+andC
det ecti on inThin Pre pPapt estvialsisinde pendentofcyto lo IN 3+Amo ngW omenWithH PV -Posit ive andHPV-Ne gativeLSIL
gic sam pl ingoft het ransf ormationzone.G ynecolOncol20 07 ;
Pap Results. J Low Genit Tract Dis 2013;17:S43YS49.
107:231Y5.
68. Katki HA, Gage JC, Schiffman M, Castle PE,
56. Huang A, Quinn M, Tan J. Outcome in women with no Fet terma nB, Poit ras NE,etal.F ol low-up TestingAfte
end ocerv ic alcom po nen to ncervic al cytol ogya ftertreatment rCo l-po sco py:F ive -YearRisk of CIN2+A fteraColposco pi cDiagfor high- gr adece rv ica ld ysplasi a. AustN ZJOb stetGynaecol
nosis of CIN 1 or Less. J Low Genit Tract Dis 2013;5:S69YS77.
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69. Massad LS, Collins YC, Meyer PM. Biopsy correlates
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NE, Cheun gL, etal.C erv icalcance rr iskfo rw omenundersystem. Gynecol Oncol 2001;82:516Y22.
goi ngcon cur rentte sti ngforhuma np apill om avirusandce r70. Alvarez RD, Wright TC. Effective cervical neoplasia
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71. Dunn TS, Burke M, Shwayder J. A see and treat
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Pap smears. J Lower Gen Tract Dis 2003;7:104Y6.
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59. Castle PE, Rodrguez AC, Burk RD, Herrero R, Wacholder Poi trasN E,L oreyT,eta l. Five-y ear riskofcer vicalcance r
and CIN3 for HPV-posit iv eandHP V-n egativehi gh-gradePa pre S,A lfaroM ,et alforthePr oye ctoE pid emiolo gi coGuanacaste
(PE G)Grou p.S horttermpe rsi sten ceo fhumanp ap illomavirusa nd
sults. J Low Genit Tract Dis 2013;17:S50YS55.
ris kofcer vic alprecance ran dcan cer :popula ti onbasedcohor t
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stu dy.BMJ .20 09;339:b25 69. doi: 10. 1136/bm j. b2569.
WuL Y,ZhangeX ,et al.Col pos copicall ydi recte dbiops y,
ran domcervic alb iopsy, and endocerv ica lcure ttagei nth edi
60. Rodriguez AC, Schiffman M, Herrero R, Wacholder S, -a gnosisofC erv icalin tra epitheli aln eopla siaIIo rwo rse.Am J
Hil desheimA, Cas tlePE,eta lf orthePr oy ectoEpide miologico
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Obstet Gynecol 2004;191:430Y4.
and implicati ons forclinic al focuson pe rsistenti nfections.J
74. Gage JC, Hanson VW, Abbey K, Dipery S, Gardner S,
Natl Cancer Inst 2008;100:513Y7.
Kubota J, et al. Number of cervical biopsies and sensitivity of
61. Stoler MH, Wright TC, Sharma A, Apple R, Gutekunst colposcopy. Obstet Gynecol 2006;108:264Y72.
K,W rightT L.H igh-ri skh umanpa pi lloma vi rustestingin
75. Guido R, Schiffman M, Solomon D, Burke L for the
wom enwith ASC -UScyt olo gy:res ul tsfro mt heATHENA
ASC US/LS IL TriageStu dy (ALTS)G ro up.Po s t-c olposcop
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HPV study. Am J Clin Pathol 2011;135:466Y75.
man ageme nt strategie sf orwomen re ferre d wit hlow-grade
62. Einstein MH, Martens MG, Garcia FA, Ferris DG, squ amous in traepithe li allesio ns ofhum a npa pillomavirus
Mit chellAL, Day SP,etal .Cl inical val idatio noftheCervis t DNA -posi ti veatypica ls quamous ce llsof u nde terminedsig-n ifican ce:at
aH PVHRand1 6/1 8genoty pin gtests for useinw omenwith
ASC-US cytology. Gynecol Oncol 2010;118:116Y22.
63. Gage JC, Schiffman M, Solomon D, Wheeler CM,
Cas tleP E.C omparison of measure me ntsofhu manpapill
omav irus per sistencef or postcol po scopics urveillanc efo
2010;19:1668Y74.
2003;188:1401Y5.
76. Lee KR, Darragh TM, Joste NE, Krane JF, Sherman
ME, Hur ley LB,etal .At ypica lgl andul arc ellsofundet ermin
ed
rcersig vica
nif ica
lp recancerousl
nce(AGU S): es
inter
ions.
obsCancerEpidemiolB
erver rep roducibilit
iomarkersPr
yincer vic al
ev.sm earsandc
Pathol 2002;117:96Y102.
S26
&
MASSAD ET AL.
77. Davey DD, Neal MH, Wilbur DC, Colgan TJ, Styer United States. Relation to incidence and survival. Cancer.
PE, ModyD R.B ethe sda 2001im ple mentat ion andreport i 2005;103:1258Y64.
ng
91. Bull-Phelps SL, Garner EI, Walsh CS, Gehrig PA, Miller
rat es:20 03p ract ice sofpar tic ipants int heCollege ofAm er
SchorgeJO.F
ert ility- spa rings
urg eryin1 01w omenwith
-i canPa tho logi sts Interl abo ratory Com parisonPr ogra minDS,
Cervico
vagi nalCytology.Ar
chP atholLabMed2004;
128:
ade nocarcinoma ins ituoft hec ervix .Gy necolO nco l2007;
1224Y9.
107:316Y9.
78. Zhao C, Florea A, Onisko A, Austin RM. Histologic
92. Costa S, Venturoli S, Negri G, Sideri M, Preti M,
fol low- up result si n662pa ti entswi thP aptestfindingsof
Pes aresi M, etal.Fact or spred ic tingth eo utcom eofconse
aty pica lg landul ar cells: re sultsf rom alargeacademicwome r- vativ el ytreateda de nocar ci nomain si tuoft heuterinece rv ix :
ns hosp it allabo ra toryem pl oyings ens itivescreeningmethod s.
an analysis of 166 cases. Gynecol Oncol 2012;124:490Y5.
Gynecol Oncol 2009;114:383Y9.
93. van Hanegem N, Barroilhet LM, Nucci MR, Bernstein
79. Sharpless KE, Schnatz PF, Mandavilli S, Greene JF, M,F eld manS.Fe rt ility-spar ing treat men tinyoungerwo men
wit had enocarc in omainsituo fth ecerv ix. GynecolOncol
Sorosky JI. Dysplasia associated with atypical glandular cells
on cervical cytology. Obstet Gynecol 2005;105:494Y500.
2012;124:72Y7.
80. Castle PE, Fetterman M, Poitras N, Lorey T, Shaber
94. Lea JS, Shin CH, Sheets EE, Coleman RL, Gehrig PA,
R,K inneyW .Re lationshi po fatypic al gland ul arcellcyt olo Dus kaL R,e tal. End ocervi cal curetta gea tconiz ationtopr egy, agean dhu manpapill om avirusd et ectio nt ocervical andend
- sid ualc erv icalad eno carcino mai nsitu. GynecolOn col
dic otre
metrial cancer risks. Obstet Gynecol 2010;115:243Y8.
81. Simsir A, Carter W, Elgert P, Cangiarella J. Reporting
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cli nicalu se fulnes so fBethe sd a2001.AmJCl in Pathol2005;
123:571Y5.
82. Schlecht NF, Platt RW, Duarte-Franco E, Costa MC,
Sob rinhoJP, Pra doJC, eta l.Humanpapill om aviru sinfectio nandtime top rogre ssi onandregressi on ofcer vicalintraepithelial neoplasia. J Natl Cancer Inst 2003;95:1336Y43.
83. Sideri M, Iqidbashian S, Boveri S, Radice D, Casadio C,
Spolti N, et al. Age distribution of HPV genotypes in cervical
intraepithelial neoplasia. Gynecol Oncol 2011;212:510Y3.
84. Trimble CL, Piantadosi S, Gravitt P, Ronnett B, Pizer E,
Elk oA,etal .Sp ontaneousr eg ression of high-gr ad ecerv ical
dys plasia: eff ectsofhuma np apillom av irustyp ea ndHLA
2002;87:129Y32.
APPENDIX A: ADDITIONAL COAUTHOR

PARTICIP AN TS,ACKNOWL EDGEDNONAUTHOR
DELEGATE S, ANDPARTICI PATING
ORGANIZA TI ONS
SeeApen di x2,avilb leon
ineath p: /links.w w.com/
LGT/A10, fo rfinacl disclourenfmat romthecau hordelgats.
Deborah Arrindell; James R.

Coautho rDelegates :
Bentley ,MD;Moniqu eA.Be rtrand,MD;L oriA.
Boardman, MD; Philip E. Castle, PhD, MPH; David
Chelmow,M D;J anieDa dd ario,MS N,WH NP-B C;
DianeD.Da vey ,MD;Li nd aDoming uez, CNP, RN;
LeviS.Dow ns, Jr.,MD ;P atricia Font aine ,MD,MS;
phenotype. Clin Cancer Res. 2005;11:4717Y23.
JuliaC.Ga ge, PhD,MP H; Francis coA. R.Ga rcia,M
85. Petersen S, Belnap C, Larsen WI, Farley J. Grading of
D,
squ amousdys pl asiain en docerv ica lcuret ta gespeci mens:Th
ec aseforco ns ervati ve manage men tofmil de ndocerv icaldys- MPH;Mohie dea nGhofr an i,MD,MB A;Ri char dS.
Guido,MD; Eri cC.Hua ng ,MD,PhD ;Ver sieJ ohnso
plasia. J Reprod Med. 2007;52:917Y21.
n86. Gage JC, Duggan MA, Nation JG, Gao S, Castle PE.
Mallard,P hD, ARNP;E li zabethA .Kos tas- Polston,
Com para tiv erisko fhi gh-gra deh ist op atholo gydiagnosisf
PhD,
ollow ing aCIN1f ind ingine ndo cer vi calcur ettagevs.cervic APRN,WHNP
al
-BC ;Rober tK urman,M D;Su sanM .
McFaul,MD ;De borahL .N ucatola ,MD; R.Pa tricia
biopsy. J Lower Genit Tract Dis 2012;17:137Y41.
P.
87. Ostor AG. Natural history of cervical intraepithelial
Power,MD; Wal terPre nd iville, MD;D ebbi eSaslow
neoplasia: A critical review. Intern J Gynecol Pathol 1993; ,PhD;Kar enS hea,MS N, WHNP-BC ;Mar yK.S idawy,MD;Ma
12:186Y92.
88. Holowaty P, Miller AB, Rohan T, To T. Natural history
of dysplasia of the uterine cervix. J Natl Cancer Inst 1999;
91:252Y8.
knowledged:VickiB.Benard,PhD;NataliaComela,PhD;
MariBethGagnon,MSCT(ASCP)HTL;AnnLaros,
Poi trasN E,L oreyT,eta l. Five-Y ear RiskofRec urrenceAf
MD;MonaSaraiya,MD,MPH;ElizabethR.Unger,PhD, MD; andRose H. Xu,Pharm
ter
mericCot
anAcaestin
demyofPgiarticnP
ipatinost
gOrgtreatment
anizationsMana
F amilyPh
ys icians;A
meri can
Tre atmen tof CIN2,CIN3 ,o rAIS:P erf ormanceof HPVand:A
Pap
ge ment.JLowG
enit
Tract Dis 2013;17:S78YS84.
90. Sherman ME, Wang SS, Carreon J, Devesa SS. Mortality trends for cervical squamous and adenocarcinoma in the
American Cancer Society; American College Health
Association; American College of Obstetricians and

Gynecologists; American Social Health Association;
American Society for Colposcopy and Cervical Pathology; American Society for Cytopathology; Association
of Reproductive Health Professionals; CDC - Division of
Cancer Prevention and Control; CDC - Division of
High-Consequence Pathogens and Pathology; CDC Division of Laboratory Science & Standards; College of
American Pathologists; Food & Drug Administration;
International Federation for Cervical Pathology and
Colposcopy; International Gynecologic Cancer Society;
National Cancer Institute; Nurse Practitioners in
Womens Health; Planned Parenthood Federation of
America; Society of Canadian Colposcopists; Society of
Gynecologic Oncologists; Society of Obstetricians and
Gynaecologists of Canada; and Women Veterans Health
Strategic Healthcare Group.
APPENDIX B: DEFINITION OF TERMS

Colposcopy is the examination of the cervix, vagina, and,
in som einstancest he vul va,with acolpos copeaft erth e
ap pli cationofa3% to 5%a ceticac idsolut ioncoup led
wi tho btainingcol po sco pically directe dbiopsi esof all
le sio nssuspected of rep resenti ngneopl asia.
in dic atesthatthe en tir eAdequ atecolp oscopy
sq uam ocolumnarju nc tio nandthe margins ofanyvi sible lesion can be visualized with the colposcope.
&
S27
is assessment for cervical disease using a

Co -testing
co mbinationo fcy tologyan dHPVtes tinga tthesame
time, regardless of the cytology result.
Reflex HPV testing is the performance of HPV testing
on lyi nresponseto an abn ormalitytost ra tifyrisk an d
gu ide furthermana ge men t.
Endometrial sampling includes obtaining a specimen
forhisto logiceval u ationusingan endometria lbiopsy,
dilation andcurett a ge,orhystero scopy.
Endocerv icalsampl i ng
includes obtaining a specimen
foreithe rhistolog i cevaluationu singan endocervic al
curetteo racytobru s horforcytolo giceva luationusi ng
acytobru sh.
is the process of evaluating

En doc ervical as sessment
th een docervi ca lcanalforthepresenceofn eoplasia
using either a colposcope or endocervical sampling.
Diagnostic excisional procedure is the process of obtaining a specimen from the transformation zone and
endocervical canal for histologic evaluation and includes
laser conization, cold-knifeconization, loop or needle electrosurgical excision, and loop electrosurgical conization.
are those that carry lower risk
Les serab norm aliti es
ofC IN3+t hano therr esult s.Theseincl udenegative
cytology with either HPV-16 or HPV-18 or persistent
untyped oncogenic HPV, ASC-US, and LSIL.
HPV, human papillomavirus; CIN, cervical intraepit helia lneoplasia;ASC- US,a typicals quamouscells
of
unde termi nedsignificance ;LSI L,low-gr adesquamousintra epithelia

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Box 1. Essential Changes From Prior Management

risk of CIN 3+ of only 8/10,000 (12). Although this low

Management strategies incorporate HPV testing based

ASCCP Guidelines Update

(oncogenic) HPV types. Testing for low-risk (nononcogenic)

future pregnancies. Young women have high regression

21Y24 years is 1.4/100,000, and almost 55,000 cytology

In the 2001 guidelines (4), separate recommendations

negative HPV tests appears to be low (47). Unsatisfactory

MANAGEMENT OF ABNORMAL SCREENING TESTS

Management of Women With

ASCCP Guidelines Update

For women aged 30 years and older who are co-tested

Cytology Reported as Negative but With

CIN 3+ risk (53). A recent meta-analysis found that

recommended (BII). If HPV type 16 and type 18

Management of Women Testing HPV Positive but

Although not indicated for younger women, co-testing is

ASCCP Guidelines Update

5-year risk of CIN 3+ after ASC-US among women aged

Triage using HPV genotyping was considered. Women

No new information that would change the 2006

inadequate colposcopy (AII) but is acceptable for women

ASC-US in Special Populations

Women Aged 65 Years and Older. Postmenopausal

Pregnant Women. Management options for pregnant

For women with ASC-US who are aged 21Y24 years,

ASCCP Guidelines Update

Low-Grade Squamous Intraepithelial Lesion

co-testing after an additional 3 years is recommended.

For pregnant women with

examinations during pregnancyare unacceptable for these

recommended. If either the HPV test is positive or repeat

ASCCP Guidelines Update

LSIL (68, 69), although risk is lower than that following

colposcopy in some 2% of women with HSIL, although

result obtained at co-testing (BII). Accordingly, reflex

HSIL in Special Populations

Atypical Glandular Cells, Cytologic Adenocarcinoma

Women Aged 2124

An AGC interpretation is poorly reproducible (76) and

ASCCP Guidelines Update

Management of Women With AGC or Cytologic AIS

is not recommended, and triage using repeat cervical

Failure to detect CIN 2+ at colposcopy in women

ASCCP Guidelines Update

or on the cervix (EII). Hysterectomy as the primary and

that the colposcopic examination is adequate and the

ASCCP Guidelines Update

excisional procedure is recommended for women with

Follow-up with HPV testing is unacceptable (EII). For

For women treated for

ASCCP Guidelines Update

negative, retesting in 3 years is recommended (BII). If

with a histologic diagnosis of CIN 2, CIN 3, or CIN 2,3

ADENOCARCINOMA IN SITU (AIS)

(BIII). Conservative management is acceptable if future

The effect of HPV vaccination on large cohorts over

ASCCP Guidelines Update

benefits on a more individualized level than consensus

Force. Screening for cervical cancer: U.S. Preventive Services

1. Solomon D, Davey D, Kurman R, Moriarty A,

hysterectomy after loop conization: increasing age and severity