KaiserPermanenteNorthernCaliforniaMedicalCarePlanprovidedevidenceonriskafterabnormaltests.Wheredatawereavailable,guidelinesprescribedsimilarmanagementforwomenwiths imi lar r i sks forC IN3,AIS ,andcancer .Mostpriorguidelineswerereaffirmed.Examplesofupdatesin-clude:Humanpapillomavirus Ynegativeatypicalsquamouscellsofundeterminedsignificanceresultsarefollowedwithco-testingat3yearsbeforereturntoroutinescreeningandarenotsufficientforexitingwomenfromscreeningatage65years;womenaged21 Y24yearsneedlessinvasiveman-agement,especiallyforminorabnormalities;postcolposcopymanagementstrategiesincorporateco-testing;endocervicalsamplingreportedasCIN1shouldbemanagedasCIN1;unsatisfactorycytologyshouldberepeatedinmostcircum-stances,evenwhenHPVresultsfromco-testingareknown,whilemostcasesofnegativecytologywithabsentorinsuf-
and
ficientendocervicalcellsortransformationzonecomponentcanbemanagedwithoutintensivefollow-up. h
*ModifiedfromGrossPA,BarrettTL,DellingerEP,etal.Purposeofqualitystandardsforinfectiousdiseases.InfectiousDiseasesSocietyofAmerica.ClinInfectDis1994;18:421.98.KishMA.Guidetodevelopmentofpracticeguidelines.ClinInfectDis2001;32:851 Y Theassignmentofthesetermsrepresentsanopinionratifiedbyvoteduringthe2012consensusconference.
ASCCPGuidelinesUpdate & S3
Multilizer PDF Translator Free version - translation is limited to ~ 3 pages per translation.
Multilizer PDF Translator Free version - translation is limited to ~ 3 pages per translation.
similar management strategies were prescribed for sim-ilar levels of risk (12, 13). Guidelines cannot be devel-oped for all situations. Clinical judgment should alwaysbe applied when applying guidelines to individual pa-tients. This is especially true for guidelines based on lessrobust evidence.
In 2012, the Lower Anogenital Squamous Terminol- og y(LAS T)P rojec tcreatedne wtermino logyforHPV- re 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 rec- ommendatio nsareavai lab leattheAS CCPwebsite (www.asccp .org/cons ens us2012).A glossaryof terms usedintheg uidelines isi nAppendix B.
In the 2006 ASCCP guidelines,(6,7) several pathwaysconcluded by returning women to ‘‘routine screening.’’ Box 2.
This term was not defined, but in 2006, screeningguidelines prescribed cytology at shorter intervals thannow recommended. Current 2011 screening guidelinesrecommend either 3-year cytology intervals or, forwomen aged 30Y(10, 11). These multi-year intervals are safe only when
64 years, 5-year co-testing intervals
risk for the development of CIN 3+ during the yearsbetween testing is low (10, 11). For example, womenaged 30Y64 years with a negative co-test have a 5-year
risk of CIN 3+ of only 8/10,000 (12). Although this lowlevel of risk can be achieved among women with nega-tive screening histories, for those with some abnormal-ities, risk for CIN 3+ remains elevated for years, evenafter treatment and even after initial negative surveil-lance. After some abnormalities, current follow-up dataare insufficient to define a pathway to return to 5-yearroutine 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 endocervi- calsa 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 though gra 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 rade squ 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 sen- sitivity,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 eer- reviewedsc 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 de- lines‘‘HPV testing’’r efersonlyto tes tingfor high-ris k
Box 1. Essential Changes From Prior ManagementGuidelines*
& Cytology reported as negative but lacking endocervical cells can bemanaged without early repeat.
& CIN 1 on endocervical curettage should be managed as CIN 1, not as apositive ECC.
&&Cytology reported as unsatisfactory requires repeat even if HPV negative.Genotyping triages HPV-positive women with HPV type 16 or type18 to earlier colposcopy only after negative cytology; colposcopy isindicated for all women with HPV and ASC-US, regardless ofgenotyping result.
& For ASC-US cytology, immediate colposcopy is not an option. The serialcytology option for ASC-US incorporates cytology at 12 months, not6 months and 12 months, and then if negative, cytology every 3 years.
& HPV-negative and ASC-US results should be followed with co-testing at3 years rather than 5 years.
& HPV-negative and ASC-US results are insufficient to allow exit fromscreening 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-onlystrategies are now limited to women younger than 30 years, butco-testing is expanded even to women younger than 30 years in somecircumstances. Women aged 21-24 years are managed conservatively.
*Prior management guidelines were from the ‘‘2006 Consensus Guidelines for theManagement of Women With Abnormal Cervical Screening Tests’’ (6). Prior guidelinesnot changed were retained.
A recent consensus conference (the Lower Anogenital SquamousTerminology [LAST] Project convened by the College of AmericanPathologists and the American Society for Colposcopy and CervicalPathology) adopted a two-tier terminology that incorporates ancillarytests and other criteria to distinguish indeterminate lesions as high gradeor low grade. Until a comprehensive evidence review and consensusguidelines development process can be conducted, histopathologyresults reported as low-grade squamous intraepithelial lesions (LSIL)should be managed as cervical intraepithelial neoplasia (CIN) 1 andthose reported as high-grade squamous intraepithelial lesions(HSIL) should be managed as CIN 2,3 (14).
(oncogenic)HPV types. Testing for low-risk (nononcogenic)HPV types has no role in the evaluation of women withabnormal cervical cytologic results.
Both ablation and excision effectively treat CIN.Randomized trials comparing different modalities showsimilar efficacy (17Yto 95%, and most failures occur within 2 years (21),
20). Efficacy rates range from 90%
although cancers can develop up to 20 years aftertreatment (22). Margin status is a convenient predictorof recurrence and a traditional risk marker, although itdoes not appear to be an independent risk factor (23,24). Nonsurgical therapies, including topical agents andtherapeutic 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 ficthancy- t olog yinpost tr eatmentfo llow-upand itma yresultin 21Y
earlier diagnosis of persistent or recurrent disease (25).Protocols for follow-up after treatment of CIN havenot been evaluated as primary interventions in ran-domized trials.
Under the 2011 screening guidelines, women follo wed afte rpositive HPVtestsbut negativecytology werer efe rred tocolposc opyonlyifth eyhadLSILor mores eve recy tologyora positiveHPV testduring surve ill ance co-testin g(10).Howev er,only0.04%ofal l women age d30- 64yearsin theKPNCdata basehad HPV-n ega tive ASC-USaft eranHPV-pos itive,cytology negat ive resu lt(26),so referringth esewomenforcol - pos copywill bur denca res ystemsmi nimally.Thus, for simp li city,curre ntgu id elin esr ecom mendcol poscop y forany po s itiveHPV tes tora nyabnormalcytology duringfoll ow-up .
Studies of the effect of treatment on future pregnancy areconf li cti ng,alt ho ughmanyin di catean approxi- matelyt wo -fo ldincr ea seinprete rm delive ryrisk
(27Y29). Although not proven, this is presumed to re-sult from deficient cervical stroma, and risk appears toincrease with the volume and number of excisions (30).However, many studies were done in countries whereloop excisions are performed with larger loop sizes anddeeper excisions than most U.S. clinicians employ.Studies linking ablative treatments to preterm deliveryare even more limited and conflicting. Women withCIN may be at increased risk for preterm delivery evenwhen untreated. Nevertheless, because pregnancycomplications can be devastating, the potential benefitsof treatment should be balanced against the risk to
future pregnancies. Young women have high regressionrates for cervical disease and low cancer risk (31Y33).The term ‘‘young women’’ indicates those who aftercounseling by their clinicians consider risk to futurep r e g n a n c i e s f r o m t r e a t i n g cervical abnormalities tooutweigh risk for cancer during observation of thoseabnormalities. No specific age threshold is intended.
In 2006, guidelines recommended less aggressive ma nagem entforadol escentswith cerv icalabnormalitie s (6, 34),butthe searenowmoo tbec ausethe2011 sc reeni ngguidelin esrecommend nots creeningadoles- ce nts(1 0,11).Dele gatestothe2 012c onsensusconfer- en cecon sideredles sintensivem anag ementforother yo ungwo menwithabn ormalcytolo gy.C ervicalcancer ri skrem ainslowthr oughage25ye ars( 35),HPVis common(36), and lesionsofte nreg ress(37) .Theannual incide nceo fce rvica lca nce ramo ngU.S.w ome naged
24 years is 1.4/100,000, and almost 55,000 cytologytests must be obtained for every cervical cancer diag-nosed in this age group (35). This level of risk is 10-foldhigher than risk in adolescents and appears to be highenough to justify screening yet is low enough to allowobservation for minor cytologic abnormalities. Guide-lines for women aged 21Y24 years can be extrapolatedto adolescents inadvertently screened.
Interventions for abnormal screening tests and CIN orAIShaveothe rco nsequenc esthatare notea sil y measurable.Wo men experien ceemotion aldis tre sswhen receivingabno rma lcytolog yandHPVte stres ult s,when havingcolposc opy evenwhen findingsa renor mal ,and whenundergoin gce rvicaltr eatment.E motio nal distress isusuallyprom pte dbyuncer taintyand antic ipa tionof theunknown(38 ).M anymanag ementstra tegie sin cor- poratefollow- upw ithHPVte sting,whi chcan eli cit feelingsofsti gma andshame whenposit ivede spi tethe near-ubiquito usf requency ofHPVinfe ction (39 ,40). Theanxietyand tim erequire dforvisit stoma nag eab- normalcytolog yca nadverse lyaffectr elati ons hips, work-relateda nds choolact ivities,a ndfam ily matter s (41).Thesepot ent ialharms reinforce theco nce ptthat co lpos copya ndotherinter vent ion ssh ouldbeavoided when riskf orCIN3+isl owandwhen identifi edlesions arel ikelytor esolve.
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.
ASCCP Guidelines Update & S5
Guidelines on management apply only to women un- dergoingro ut inescreeni ngwit hade qu atevi sualizationof thecervixa nd directedsa mplin gwit ha ccept ablecollec- tioninstru me nts.Theyal soapp lyon ly towom eniden- tifiedwith ab normalitie sduri ngsc re ening .Womenwith postcoital or unexplaine dabno rmal va ginal bleeding, pelvicpain ,a bnormaldis charg e,or av isibl elesionmerit indivi dualizede valu ations.
Consensus guidelines from the ASCCP have interna- tionalinf luence.How ever ,th eyare tail oredtotheop- portunist iccervical canc ers creen ings ystemofthe UnitedSta tes,withsp ecif ict ermin olog y,diagnosticcri - teria,pat hwaystocol posc opi ctrai ning ,patientexpec-
tations and adherence, andmedicalYelsewhere must consider the guidelines in light of their
legal risks. Clinicians
own context and adapt management accordingly.
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 labnor- malities .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
other processes (44, 45). Now that most U.S. cytology isdone using liquid-based media, which can control formost obscuring factors in processing, unsatisfactory re-sults arise largely from insufficient squamous cells (46).Evidence is sparse governingmanagement of womenwithunsatisfactory cytology obtained as part of co-testing,although risk for high-grade disease in women withnegative HPV tests appears to be low (47). Unsatisfactoryresults arise largely from insufficient squamous cells (48).Some currently available HPV tests lack a control forepithelial cellularity, so a negative HPV test cannot berelied, upon as the HPV test may be falsely negative be-cause of an insufficient sample.
Specimen collection techniques to minimize unsatis- factoryc 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 Women With Unsatisfac to ryCyt ology(Fig.1) Forwomenwi th anuns atisfactorycytology resultan d no,unknown ,o raneg ativeHPVtestresult, repeatcy -
tology in 2Yusing reflex HPV testing is not recommended (BIII).
4 months is recommended (BIII). Triage
Treatment to resolve atrophy or obscuring inflammationwhen a specific infection is present is acceptable (CIII).
Figure 1.
S6 & MAS SAD ET AL .
For women aged 30 years and older who are co-testedand have unsatisfactory cytology and a positive HPVtest, repeat cytology in 2Y4 months or colposcopy isacceptable (BII). Colposcopy is recommended for womenwith two consecutive unsatisfactory cytology tests (CIII).
Cytology Reported as Negative but WithAbsent or Insufficient EC/TZ Component
Cytology reported as negative but with absent or in- sufficie ntEC/TZc om ponentha sad equa tecell ul arity forinter pretatio nb utlackse ndo cerv icalor me taplastic cells,su ggesting th atthesqu amo colu mnarju nc tionmay nothaveb eenadequ at elysampl ed. This raises co ncern formisse ddisease .R ecentlyr epo rted rateso fc ytology resultsr eporteda sn egativeb utw itha bsento ri nsuffi- cientEC/ TZcompon en thaveran ged from 10%to2 0% andarehi gherinol de rwomen(5 1,5 2).P riorgu id elines recommen dedearly re peatcyto log y(8, 9).How ev er, whilewom enwithab se ntorinsu ffi cien tEC/TZ co m- ponenthavef ewerc oncurrent cyt ologicab normalities, th eydonothaveahi ghe rrisk forCIN3+over ti methan womenwithas atisfactor yEC/ TZc omponent,aswou ld beexp ectedif true prec ancershadb eenmisse d.In stead, thelowerra teofcy tologica bnormali tyappear stooc cu r becausewomenwh osecytol og ylacksas ati sfac toryEC / TZcomponentare older ,andolder wome nhavel ower
CIN 3+ risk (53). A recent meta-analysis found thatnegative cytology had good specificity and negativepredictive value despite absent or insufficient EC/TZcomponent (54). HPV testing appears to be independentof transformation zone sampling (55) and offers anadded margin of safety for women aged 30Y64 yearsnow that co-testing is the preferred screening strategyfor that age group. An absent EC/TZ component is notassociated with an increased incidence of cervical dis-ease after treatment of CIN 2+ (56).
Management of Women With Cytology Reported asNegative but With Absent or Insufficient EC/TZ
Component (Fig. 2)
YFor women aged 21absent or insufficient EC/TZ component, routine screen-
29 years with negative cytology and
ing is recommended. HPV testing is unacceptable (BIII).For women aged 30 years and older with cytology
rep orted asne ga tivea ndw ithab sent orinsufficient EC/ TZcom pone nt andno oru nknow nHPV testre- sul t,HPV test in gispr efe rred( BIII ).Repeatcytologyi n 3ye arsis acce pt ablei fHP Vtest ingi snotperformed (BI II).I fthe HP Vtest isd onean disn egative,return to ro utinescr een ingi srecom me nded(BIII).Ifthe H PVtestisp osi ti ve ,repeat ing both testsin1y ear is acce pt able(BIII ).Genot ypingi salsoacc eptable;if HPVtype16ortype18ispresent,colposcopyis
Figure 2.
ASCCP Guidelines Update & S7
recommended (BII). If HPV type 16 and type 18are absent, repeat co-testing in 12 >months is recom-mended (BIII).
Negative Cytology With a Positive HPV Test
Although not indicated for younger women, co-testing isthe preferred screening strategy for women aged 30Y64years (10). Despite negative cytology, women with on-cogenic HPV are at higher risk for later CIN 3+ thanwomen with negative HPV tests (57). The risk of CIN 3+in HPV positive but cytology negative women is suffi-cient to justify early return for retesting. Persistent HPVpositivity increases risk still further (58, 59). However,most HPV infections are cleared, substantially reduc-ing risk of CIN 3+ (60), so observing women to allowclearance is attractive. Nevertheless, CIN 3+ does occurduring observation, requiring guidelines to balance risksarising from intervention for HPV that may yet be clearedagainst the risks of disease. This is true even for womenwith HPV infections but negative cytology. In the KPNCcohort, the CIN 3+ risk for every co-test result obtainedafter an initial HPV-positive but cytology-negative resultwas higher than risk associated with that co-test result inwomen with prior negative screening (58).
Women with HPV-16 are at particular risk for CIN 3+.Hu manp apillo mav ir us-18merit sspe cia lconsid er- ation beca useofi tsa ss ociationwi thce rvi caladen ocar- cin omas ,which are le ssefficien tlyd ete ctedbyc ytolo gy thansquamousca ncers.
Management of Women Testing HPV Positive butCytology 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).
HPV genotyping is also acceptable. If HPV-16 or HPV -18testsar ep osit ive,colposc op yisrec ommended (BI I).IfHPV-1 6a ndHP V-18testsar en egativ e,repeat co-te sti ngin1year isrecommen de d(BII).
Atypical Squamous Cells of UndeterminedSignificance (ASC-US)
ASC-US is the most common cytologic abnormality, but itcarr ie sth elow estris kofCIN3+, partlybecaus eone thirdt ot wot hird sareno tHPV-asso ciated(2,26) .In ALTS,t hr eem anag ements trategies performedsim ilarly andwer ei ncl uded insubs equentgui delines(3,4, 6). Compar ed wit hcol poscop yforallAS C-US,reflext est- ingfol lo wed byco lposco pyforHPV- positivewome n waspre fe rre dbec auseit identifie dmostCIN3les ions yetref er red many fewerw omentocol poscopy(3).A LTS wascon du cte dbef orethe 2001Bethe sdasystemupd ate, whichs ep ara tedA SC-Hcy tologyfro mtheASC-US catego ry .Fo rthi sandot herreason s,theobserve d3%
Figure 3.
S8 & MAS SAD ET AL .
5-year risk of CIN 3+ after ASC-US among women aged30 years and older in the KPNC cohort was lower thanthe 2-year risk seen in ALTS. In fact, risk was low enoughto justify annual rather than semiannual cytology assufficiently sensitive to identify women with CIN 3+ (61).
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 therisk for CIN 3+ in both groups exceeded the thresholdfor colposcopy (26). HPV-16/18 genotyping of HPV-positive women with ASC-US did not appear to lead todifferent management.
No new information that would change the 2006 gu ide lineswaside ntif iedon ASC-US inp regnantor po stm enopausalwo men.
For women with ASC-US cytology and no HPV re- sul t,rep eatc ytolog yat1year isa cc ept able(BII) .Ifthe res ultis ASC- USorwo rse,colp osc op yis recommend ed; 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 inwhom no lesions are identified (BII) and for those with an
Figure 4.
ASCCP Guidelines Update & S9
inadequate colposcopy (AII) but is acceptable for womenwith an adequate colposcopy and a lesion identified in thetransformation zone (CII).
Because of the potential for overtreatment, the rou- tineuse of dia gnosticex cis ionalprocedure ssu chasloop electro su rgi calexcisi onf orwomenwithani nit ialASC- USinthe ab sen ceofCIN2+ isu nacceptable(EI I).
ASC-US in Special Populations
Women Aged 2124 years (Fig. 5)Y
Initial Management
For women aged 2124 years with ASC-US, cytologyYalone at 12-month intervals is preferred, but reflex HPVtesting is acceptable (BII). If reflex HPV testing isperformed with ASC-US and the HPV result is positive,repeat cytology in 12 months is recommended (BII).Immediate colposcopy or repeat HPV testing is notrecommended. If reflex HPV testing is performed and isnegative, return for routine screening with cytologyalone in 3 years is recommended (BII).
Follow-Up
For women with ASC-US who are aged 21Yfollow-up with cytology at 12-month intervals is recom-
24 years,
mended. Colposcopy is not recommended. (BII) Forwomen with ASC-H or HSIL+ (HSIL, atypical glandularcells [AGC], or cancer) at the 12-month follow up, col-poscopy is recommended. For women with ASC-US or
worse at the 24-month follow-up, colposcopy is recom-mended. For women with two consecutive negative re-sults, return to routine screening is recommended. (BII)
Women Aged 65 Years and Older.women with ASC-US should be managed in the same
Postmenopausal
manner as women in the general population, exceptwhen considering exit from screening for women aged65 years and older. For those women, HPV-negativeASC-US results should be considered abnormal (AII).Additional surveillance is recommended with repeatscreening in 1 year; co-testing is preferred but cytology isacceptable (BII).
Pregnant Women.women with ASC-US are identical to those described
Management options for pregnant
for nonpregnant women, with the exception that defer- rin 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).
Postmenopausal women with Postmenopausal Women . ASC-USshouldbe manag edinthesamemanneraswomen in the general population (BII).
Figure 5.
S10 & MAS SAD ET AL .
The ASCUS-LSIL Triage Study showed that the naturalhistory of LSIL approximates that of HPV-positive ASC-US (64), suggesting that women with either should bemanaged similarly. Analysis of the KPNC dataset con-firmed that women with LSIL at ages 21Ya lower risk of CIN 3+ than older women (33, 65). Low-
24 years carry
grade squamous intraepithelial lesions are highly asso-ciated with HPV infection, with a pooled estimate ofHPV positivity of 77% (66). This rate appears toohigh to allow reflex HPV testing to select women forcolposcopy efficiently. However, when co-testing is per-formed in women 30 years of age and older, some womenhave HPV-negative LSIL. In the KPNC cohort, the riskof CIN 3+ in HPV-negative women with LSIL was low,similar to that of ASC-US alone (67).
Management of Women with LSIL (Fig. 6)
For women with LSIL cytology and no HPV test or a pos itive HPVt est, colposco pyi sr eco mmen de d(AI).Ifco - tes tings hows HPV- negative LSI L, rep eatc o- testingat 1ye arisp referred,b ut colposcopyi sacce pt able.Ifrepe at
aged 21co-testing at 1 year is elected, and if the cytology is ASC-US or worse or theHPV test is positive (ie, if the co-testingresult is other than HPV negative, cytology negative),colposcopy is recommended. If the co-testing resultat 1 year is HPV negative and cytology negative, repeat
co-testing after an additional 3 years is recommended.If all tests are negative at that time, routine screening isrecommended (BIII).
LSIL in Special Populations
Women Aged 2124 Years (Fig. 5).YLSIL who are aged 21-24 years, follow-up with cytology
For women with
at 12-month intervals is recommended (BII). Colposco- py 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 t-tage in pregnant women is unacceptable (EIII). Forpregnant women aged 2124 years, follow-up accordingYto the guidelines for management of LSIL in women
Y24 years is recommended (discussed in previousparagraph). Deferring colposcopy until 6 weeks postpar-tum is acceptable (CIII). For pregnant women who haveno cytologic, histologic, or colposcopically suspected CIN2+ at the initial colposcopy, postpartum follow-up isrecommended (BIII). Additional colposcopic and cytologic
Figure 6.
ASCCP Guidelines Update & S11
Low-Grade Squamous Intraepithelial Lesion
examinations during pregnancyare unacceptable for thesewomen (DIII).
Postmenopausal Women.management of postmenopausal women with LSIL and
Acceptable options for the
no HPV test include obtaining HPV testing, repeat cyto- lo gic test ingat6m onthsand1 2mo nths,and colpos copy (C III ).If theHPVt estisnega tiv eorifCIN isnoti den- ti fie datc olposco py,repeat cyt ologyin1 2month sis
recommended. If either the HPV test is positive or repeatcytology is ASC-US or greater, colposcopy is recom-mended (A I I ) . I f two cons e cu t i v e repeat cytology tests arenegative, return to routine screening is recommended. (BII)
Data from KPNC confirmed that a report of ASC-Hconfers higher risk for CIN 3+ over time than ASC-US or
Figure 8.
Figure 7.
S12 & MAS SAD ET AL .
LSIL (68, 69), although risk is lower than that followingHSIL. This is also true for women aged 21Yalthough their risk of CIN 3+ is lower than that for older
24 years,
women with ASC-H (33). The high rate of HPV detec-tion in women with ASC-H makes reflex HPV testingunsuitable (3). In addition, the 5-year cancer risk amongwomen with HPV-negative ASC-H is 2%, which is toohigh to justify observation (68).
Management of Women With ASC-H (Fig. 8). Forwomenwith ASC-H cytology, colposcopy is recommendedregardless of HPV result. Reflex HPV testing is notrecommended (DII).
ASC-H in Special Populations
YWomen Aged 2124 Years (Fig. 9)
Colposcopy is recommended (AII). Further managementshould follow guidelines for women aged 2124 yearsYwith 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 womenwith HSIL (69Ythe transformation zone for many women, especially
71). This justifies immediate excision of
those who are at risk for loss to follow-up or who havecompleted childbearing. Cervical cancer is found at
colposcopy in some 2% of women with HSIL, althoughrisk rises with age and is low among women aged 21Y24years, even with follow-up (33). Five-year cervical can-cer risk is 8% among women 30 years of age and older(72). Risks are modified by HPV test results: HPV-negative HSIL co-test results, although uncommon, stillcarry a 5-year risk for CIN 3+ of 29%, while 7% willdevelop cancer (72). This precludes reflex HPV triagefor HSIL. In the KPNC cohort, among women 30 yearsof age and older with HPV-positive HSIL, the 5-year riskof CIN 3+ was 50%, while the 5-year cancer risk was7% (72). When HPV results are known from co-testingfor women with HSIL, these risks may inform the choicebetween immediate diagnostic excision and colposcopyand between diagnostic excision and cytologic and col-poscopic surveillance when CIN 2+ is not identified. Thesensitivity of colposcopy for detecting CIN 2+ is lowerthan previously appreciated (73Y75), and multiple bi-opsies should be considered at colposcopy when largeconfluent or multiple discrete lesions are seen.
Management of Women With HSIL (Fig. 10). Forwomen with HSIL cytology, immediate loop electro-surgical excision or colposcopy is acceptable, except inspecial populations (BII). Triage using either a programof repeat cytology alone or reflex HPV testing is unac-ceptable (EII). For women not managed with immediateexcision, colposcopy is recommended regardless of HPV
Figure 9.
ASCCP Guidelines Update & S13
result obtained at co-testing (BII). Accordingly, reflexHPV 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‘ ‘Man- a 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).
HSIL in Special Populations
Women Aged 2124 Years (Fig. 9).Y2124 years with HSIL, colposcopy is recommended.Y
For women aged
Immediate treatment (ie, see-and-treat) is unacceptable.(AII) When CIN 2+ is not identified histologically, ob-servation for up to 24 months using both colposcopy andcytology at 6-month intervals is recommended, providedthe colposcopic examination is adequate and endocervi-cal assessment is negative or CIN 1 (BIII). If CIN2,CIN3,or CIN 2,3 is identified histologically, managementaccording to the 2012 consensus guideline for the man-agement of young women with CIN 2, CIN 3, or CIN 2,3is recommended (see ‘‘Management of WomenWith CIN
2, CIN 3, and CIN 2,3’’). (BIII) If during follow-up a high-grade colposcopic lesion is identified or HSIL cytologypersists for 1 year, biopsy is recommended. (BIII) If HSILpersists for 24 months without identification of CIN 2+, adiagnostic excisional procedure is recommended. (BIII) Adiagnostic excisional procedure is recommended forwomen aged 21Yunsatisfactory or CIN 2, CIN 3, CIN 2,3, or ungraded
24 years with HSIL when colposcopy is
CIN is identified on endocervical sampling. (BII) Aftertwo consecutive negative cytology results and no evidenceof high-grade colposcopic abnormality, return to routinescreening is recommended (BIII).
Atypical Glandular Cells, Cytologic AdenocarcinomaIn Situ, and Benign Glandular Changes
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 gad- en oca rcinomasofthee nd ometri um,cervix,ov ary, fal- lo 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
Figure 10.
S14 & MAS SAD ET AL .
appellation, AGC cytology is most commonly associ-ated with squamous lesions including CIN 1. However,glandular and squamous lesions often coexist, withCIN found in approximately half of women with AIS(79Y81), so identification of CIN does not preclude AISor adenocarcinoma. Although cervical adenocarcino-ma is HPV associated and can be detected with HPVtesting, endometrial cancer is not, so reflex HPV testingdoes not identify a subgroup of women who need lessinvasive assessment. A negative HPV test can be usefulin identifying women at greater risk for endometrialrather than cervical disease (80). Endometrial cancerrisk is low in young women without endometrial cancerrisk factors but is substantially greater in older womenand 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).
is not recommended, and triage using repeat cervicalcytology is unacceptable (DII). Endometrial sampling isrecommended in conjunction with colposcopy and en-docervical sampling in women 35 years of age and olderwith all subcategories of AGC and AIS (BII). Endome-trial sampling is also recommended for women youngerthan 35 years with clinical indications suggesting theymay be at risk for endometrial neoplasia (BII). Theseinclude unexplained vaginal bleeding or conditions sug-gesting chronic anovulation. For women with atypicalendometrial cells, initial evaluation limited to endome-trial and endocervical sampling is preferred, with col-poscopy acceptable either at the initial evaluation ordeferred until the results of endometrial and endocervicalsampling are known; if colposcopy is deferred and noendometrial pathology is identified, colposcopy is thenrecommended (AII).
Subsequent Management (Fig. 12)
For women with AGC not otherwise specified cytol-ogy in whom CIN 2+ is not identified, co-testing at12 months and 24 months is recommended. If both co-tests are negative, return for repeat co-testing in 3 yearsis recommended. If any test is abnormal, colposcopy isrecommended. (BII)
If CIN 2+ but no glandular neoplasia is identified his- to log ic all yd uringthei nitialwor ku pofawomanw ith at ypi ca len do cervical, endometri al ,orglandul arcellsnot
Figure 11.
ASCCP Guidelines Update & S15
otherwise specified, management should be according tothe 2012 consensus guidelines for the lesion found (CII).
For women with AGC ‘‘favor neoplasia’’ or endo- cer vical AISc yto logy,if invasivedis ea seisnotidentif ied dur ingth eini tia lcolpos copicworkup ,a diagnosticex- cis ionalproc ed ureisrec ommende d( AII ).
It is recommended that the type of diagnostic exci- si on alprocedure used int hiss et tingprovid eanintact sp ec imenwithint erpr eta blem ar gins(BII). Endocervica l samplingaft erex cis ioni sp referred(B II).
AGC or Cytologic AIS in Special Populations
Pregnant Women Theiniti alevaluat ionofAG Cinpregnan tw ome n shouldbe identical tothato fnonpregna nt wom en(BII), exceptth atendocer vicalcu rettageand en dom et rial bio psyareunacce pt able(EIII ).
Women Aged 2124 YearsY
It is recommended that ASCCP guidelines for manage- me nt ofAGCbefoll owed foral lwomen,inc lud ingthose ag ed 2124years(B II).Y
For asymp- Man agementofBenignGl an dularC hanges. tom aticpremenopausal wo menwit hbenignen dometrialcells, endometrial stromal cells, or histiocytes, no further evalua tionisrecommended( BII).F or postmenopaus al womenw ithbenignen dometri alcell s, endometriala s- sessme ntisrecomme nded(BI I).For po sthysterecto my pa-
tients with a cytologic report of benign glandular cells,no further evaluation is recommended (BII).
MANAGEMENT OF CIN AND HISTOLOGIC AIS
CIN 1 and No CIN Found at Colposcopy AfterAbnormal Cytology
CIN 1 is the histologic manifestation of HPV infection. Alt h ou ghm ostCIN1les ionsareassoci at edw ithonco- gen 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 CIN 1 is sim ilartothat ofHPV-positiv eA SC- USandLSIL int h ea bse nceofCIN,s uggestingsimi la rma nagement. Reg r es sio nratesareh igh,especiall yi nyo ungerwomen (32 , 64 ),a ndprogress iontoCIN2+isu nc omm on(64,84). The r is kof occultCIN3 +amongwomenwi th CIN 1at col p os cop icbiopsyis linkedtotheri sk con veyedbyprior cyt o lo gy. KPNCdatash owedsimilar,r el ati velylow5-year 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 1af t er LSI LorHPV-pos itiveASC-USha da 5-y earrisk ofC I N3 +of 3.8%,while thosewithCIN1 af ter HSIL had a 5- yea rriskofCIN 3+of15%(68).
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 sa result, wo menwit hHS IL wh odonothave im mediate di agno stic exc isio nreq u ire cl osefol low -up.Fewstudies
Figure 12.
S16 & MAS SAD ET AL .
of the natural history of HSIL managed without treat-ment have been reported, and follow-up in those islimited (68); management relies on expert opinion.
Women with minor cytologic abnormalities have simil arri skfor CIN3+whet hercolposcopy showsCIN 1orno lesi on(64 ,68).Sinc eCIN3+riskise levatedfor women with eithe rHPV-16or HPV-18orpersi stent oncog enic HPVin fectionof anytypeevenwh encytol- ogyis nega tive, guideline smustprovidef orfollow-up forwo menw ithth ese‘‘less erabnormaliti es’’evenwhen noCIN isfo und.T hese‘‘les serabnormalit ies’’include HPV-1 6orH PV-18 positivit y,persistentu ntypedonco- geni cHP V,A SC -US,and LSIL.
The management of CIN 1 in endocervical samples mer itsspecial at ten t io n.Traditiona lmanagementstr ate- giesprescr ib ede x ci sionaltherap yforwomenwith CIN onendocerv ic als a mp ling.However ,thesestrategies pre cededfullu nd ers t an dingofthehig hspontaneous reg ressionrat es ofC I N1 .Endocervica lsamplesare oft encontamin at edb y ec tocervicalle sions.Womenwith CIN1onendo ce rvi c al samplinghave alowriskfor CIN 2+(85,86)( Fu kuc h iE ,FettermanB, PoitrasN, Kin neyW,Lorey T, Lit t le RD.Riskofcer vicalprecan- cer andcanceri nw ome n wi thcervicalin traepithelial neo plasiagrad e1 one n do cervicalcure ttage.JLowGenit Tra ctDis[inpr es s]) . Cu rrentguideli nesonmanagemen t ofCIN 1onendocer vicalsampli ngdonotapp lywhen CIN2, CIN3,orCIN 2,3isspeci fiedorw hen the
lesion seen cannot be graded, as an associated invasivecancer cannot be excluded without a diagnostic exci-sion procedure.
Management of Women With CIN 1 or No LesionPreceded by ‘‘Lesser Abnormalities’’ (Fig. 13). Co-testingat 1 year is recommended (BII). If both the HPVtest and cytology are negative, then age-appropriateretesting 3 years later is recommended (cytology if ageis younger than 30 years, co-testing if 30 years of ageor older). If all tests are negative, then return to routinescreening is recommended (BII). If any test is abnormal,then colposcopy is recommended (CIII).
If CIN 1 persists for at least 2 years, either continued fo llo w -uportre atm en tisac c eptabl e(CII) .Iftreat- me nti s selected and th ecolp o scopic examin ationis ad equ a te,eithe rex ci siono r ablati onisac ceptable (A I). A diagnost ice xc ision a lproce dureis recom- me nde d ifthecol pos co picex a minati onisin adequate; th een d ocervica lsa mp lingc o ntains CIN2,C IN3,CIN 2, 3or u ngradedC IN; or thepa t ientha sbeenp reviously tr eat e d(AIII). Tre at mentm o dality should bedeter- mi ned b ythejudg men to fthec l inicia nandsh ouldbe gu ide d byexperi enc e, resou r ces,an dclini calvaluefor th esp e cificpat ien t( A1II) . Inpati entswi thCIN1and an ina d equateco lpo sc opice x aminat ion,ab lativeproce- du res a reunacce pta bl e(EI) . Podoph yllino rpodophyllin- relat ed productsa re unacceptab leforu se inthevagina
Figure 13.
ASCCP Guidelines Update & S17
or on the cervix (EII). Hysterectomy as the primary andprincipal treatment for histologically diagnosed CIN 1 isunacceptable (EII).
Management of Women With CIN 1 or No LesionPreceded by ASC-H or HSIL (Fig. 14). When CIN 2+is not ident i f i ed hi s to logica l ly ,eitheradiagnosticexcisionalprocedure or observation with co-testing at 12 months and24 months is recommended, provided in the latter case
that the colposcopic examination is adequate and theendocervical sampling is negative. (BIII). In this circum-s t an c e , i t i s a c c ep t ab l e t o r e v i ew the cytologic, histologic,and colposcopic findings; if the review yields a revisedinterpretation, managementshould follow guidelines forthe revised interpretation (BII). If observation with co-testing is elected and both co-tests are negative, return forretesting in 3 years is recommended. If any test is abnor-mal, repeat colposcopy is recommended. A diagnostic
Figure 14.
Figure 15.
S18 & MAS SAD ET AL .
excisional procedure is recommended for women withrepeat HSIL cytologic results at either the 1-year or 2-yearvisit (CIII).
Management of Women With CIN 1 on EndocervicalSampling. When CIN 1 is detected on endocervical samp lin g af terlesse ra bnormalitiesbutnoCIN2 +is dete cte d in colposco pi cbiopsies,managements hould foll owA S CC Pmanagem en tguidelinesforCIN1,wi th th ead d it ionofrep ea tendocervicalsampling in12 mont hs( B II ).Forwom en withCIN1onendocervica l samp lin g an dcytolog yr eportedasASC-H,HSIL,o r AGC, orw i th acolposc op icbiopsyreportedasCIN 2+, mana gem e nt accordin gt otheASCCPmanagement guid eli n es forthesp ec ificabnormalityisreco mmended (BII ).F o rw omennott re ated,repeatendocervic alsam pling atthetimeofev alu at ion fo rtheotherab no rmalityis r ecommende d(BII).
CIN 1 in Special Populations
Women Aged 2124 Years (Fig. 15).Y2124 years with CIN 1 after ASC-US or LSIL cytology,Y
For women aged
repeat cytology at 12-month intervals is recommended.
Follow-up with HPV testing is unacceptable (EII). Forwomen with ASC-H or HSIL+ at the 12-month followup, colposcopy is recommended. For women with ASC-US or worse at the 24 month follow up, colposcopy isrecommended. After two consecutive negative tests,routine screening is recommended. (BII)
For women aged 21Yor HSIL cytology, observation for up to 24 months using
24 years with CIN 1 after ASC-H
both colposcopy and cytology at 6-month intervals isrecommended, provided the colposcopic examination isadequate and endocervical assessment is negative (BIII). IfCIN 2, CIN 3, or CIN 2,3 is identified histologically,management should follow the guideline for the man-agement of young women with CIN 2, CIN 3, or CIN 2,3(BIII, see ‘‘Management of Women With CIN 2, CIN 3,and CIN 2,3’’). If during follow-up a high-gradecolposcopic lesion is identified or HSIL cytology persistsfor 1 year, biopsy is recommended (BIII). If HSIL persistsfor 24 months without identification of CIN 2+, a diag-nostic excisional procedure is recommended (BIII). Whencolposcopy is inadequate or CIN 2, CIN 3, CIN 2,3 orungraded CIN is identifiedon endocervical sampling,adiagnosticexcisionprocedure is recommended (BII).
Regardless of antecedent cytology, treatment of CIN 1in women aged 21Y24 years is not recommended (BII).
Figure 16.
ASCCP Guidelines Update & S19
For pregnant women with a histo- log icdiagno sisof CIN1 , follow-upwit houttreat me nt isr ecommend ed(BI I).T r eatmentofpre gnantwome n for CIN1isun accep tabl e .
CIN 2, CIN 3, and CIN 2,3
While distinction between CIN 2 and CIN 3 is difficult inind ividualcase s,regre ssi o nra tes a re lowerandpro- gress iontocancer morecom mon f orw ome n wi thCIN3 thanf orthosewith CIN2(87 ,88 ) .Ce rvi c al intraepithel ial neopl asia2remain sthecon sen s ust hre s ho ldfortreatme nt int heUnitedSta tes,exc ept i nsp eci a lc ircumstances . Women withunambig uousCIN 3ha v eth eim m ed iate precu rsortoinvas ivecanc era n dsh oul d no tbeobserved, regar dlessofageo rconcer nab o utf utu r ef ertility.
After treatment for CIN 2+, recurrence risk remains wella bovethato fwo men wit hnegativec o-te stresults throu ghoutobse rva tio npe riodsthath aveb eenreported todat e(89).Aft ert won ega tiveco-tes tsin thefirst 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 hetherrou- tines creeningm ayb eap pro priateafte rthr eeormore negat iveco-tes tsi sun cle ar.
The objective of screening during pregnancy is to iden-tify cervical cancer. Cervical intraepithelial neoplasia 3
does not pose a risk to the pregnancy and poses no im-mediate risk to the mother. Treatment during pregnancycarries substantial risk for hemorrhage and pregnancy loss.
Management of Women With CIN 2, CIN 3,and CIN 2,3 (Fig. 16)Initial Management.agnosis of CIN 2, CIN 3, or CIN 2,3 and adequate
For women with a histologic di-
colposcopy, both excision and ablation are acceptable treatmentmo dali ties,exc ept inpregna ntw omenand youngwomen( AI). Adiagnos tic excision alp rocedure isrecommend edfo rwomenwi thr ecurrent CIN 2,CIN 3,orCIN2,3( AII) .Ablatio nis unaccept abl eandadi- agnosticexc isio nalproce dur eisrecom men dedfor 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 graded(AII) .Obs ervation ofC IN2,CIN3 ,or CIN2,3 withsequent ialc ytologya ndc olposcop yis unaccept- able,except inpr egnantwo men andyoung wom en(EII). Hysterectom yisu naccepta ble asprimar yth erapyfor CIN2,CIN3,o rCIN 2,3(EII) .
For women treated for Fol low-U pAfterT reatment. CIN 2,CIN 3,orCIN 2,3,co-testin gat12 monthsand24 months is recommended (BII). If both co-tests are
Figure 17.
S20 & MAS SAD ET AL .
Pregnant Women.
negative, retesting in 3 years is recommended (BII). Ifany test is abnormal, colposcopy with endocervicalsampling 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 apositive HPV test is unacceptable (EII).
If CIN 2, CIN 3, or CIN 2,3 is identified at the mar- gi 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 du r e, reasses smentusing cytologyw it he nd ocervicalsampl ingat
4repeat diagnostic excisional procedure is acceptable (CIII).Y6monthsaftertreatmentispreferred (BII). Performing a
H y s t e r e c t om y i s a c c e p t a b l e i f a repeat diagnostic proce-dure is not feasible (CIII).
A repeat diagnostic excisional procedure or hysterec- t 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
Young Women (Fig. 17).tologic diagnosis of CIN 2,3 not otherwise specified,
For young women with a his-
either treatment or observation for up to 12 months usingb othcolpos co pyandcytolo gya t6 -m on thin- terval sisaccept ab le,provided col po sc op yisadequate. (BIII) Whenahist ol ogicdiagnos iso fC IN 2i sspecified forayo ungwoman, ob servationis pre fe rr ed buttreat- mentis acceptabl e. Ifthecolpos cop ic ap pe aranceofthe lesi onworsenso rif HSILcyto lo gyorahi gh-grade co lp oscopiclesi onpersis tsfor1year ,r epeatbiopsyis re comm e nded(BIII) .
After two consecutive negative cytology results, an ad- ditio nal co-test1yea rlateris recommen ded(BIII ). Ifthe addit ion alco-testis negative ,thenrep eatco-te st ingin 3year sis recommended (BIII).C olposcop yisrecom me nded ife ith erthe2-year or5-year co-testi sabnorma l( BIII).
Treatment is recommended if colposcopy is inade-quate, if CIN 3 is specified, or if CIN 2 or CIN 2,3persists for 24 months (BII). For women aged 21Y24years who are treated, follow-up according to ASCCPguidelines for treated CIN 2, CIN 3, or CIN 2,3 isrecommended (BIII).
Treatment is recommended if CIN 3 is subsequently identifie do rifCIN2,CIN 3, orC I N2 ,3persistsfor 24months( BI I).
In the absence of invasive disease or Pr egn antWome n. ad van cedpreg na ncy,addi tionalc olposcopica ndcyto-logic examinations are acceptable in pregnant women
with a histologic diagnosis of CIN 2, CIN 3, or CIN 2,3at intervals no more frequent than every 12 weeks (BII).Repeat biopsy is recommended only if the appearance ofthe lesion worsens or if cytology suggests invasive can-cer (BII). Deferring reevaluation until at least 6 weekspostpartum is acceptable (BII). A diagnostic excisionalprocedure is recommended only if invasion is suspected(BII). Unless invasive cancer is identified, treatmentis unacceptable (EII). Reevaluation with cytology andcolposcopy is recommended no sooner than 6 weekspostpartum (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 nof thedesire dd ept ho fex cis ion.AI Scanb emultifocalan d dis continuou s, son eg ati vem argins onane xcisionspeci- men 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.
For these reasons, total hysterectomy remains the tre atmen tofchoic einwo menwhohaveco mpleted chi ldbea ring.For women whowishtomai ntainfe rtility, obs ervat ionisano ption ,althoughitc arriesa lessthan 10%r is kofper si stent AIS anda smallriskofcancereven
when excision margins are negative (91Y3). Like marginstatus, endocervical sampling at the time of an excisionalprocedure also predicts residual disease (94). Moreover,a negative HPV test after treatment identifies women atlow risk for persistent or recurrent AIS (94). In 2001,knife conization was favored over loop excision becausemargin status and the interpretability of margins arecritical to future treatment planning. In 2006, wordingwas changed to allow diagnostic excision using any mo-dality, but care must be taken to keep the specimen intactand margins interpretable, avoiding fragmentation of thespecimen, including ‘‘top-hat’’ serial endocervical exci-sions. This may require use of larger loops than thoseemployed to excise visible squamous lesions.
Management of Women With AIS (Fig. 18)
Hysterectomy is preferred for women who have com- pletedchildb ea ringandha vea histo log icdi agnosisofAIS onaspecim en fromadiag nos ticex cis iona lprocedure
ASCCP Guidelines Update & S21
(BIII). Conservative management is acceptable if futurefertility is desired (AII). If conservative management isplanned and the margins of the specimen are involved orendocervical sampling obtained at the time of excisioncontains CIN or AIS, reexcision to increase the likelihoodof complete excision is preferred. Reevaluation at 6months using a combination of co-testing and colposcopywith endocervical sampling is acceptable in this cir-cumstance. Long-term follow-up is recommended forwomen who do not undergo hysterectomy (CIII).
RECOMMENDATIONS FOR FUTURE RESEARCH
Literature review for the 2012 ASCCP Consensus Guide-lines Conference identified several issues important topatient management that lack high-level evidence.
Follow-up is insufficient to determine posttreatment outcomeso ro ptimallong-t er mfollow-u pintervals 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 expertopi ni onandshouldb em odifiedas evidencebe- comesavai la ble.
Follow-up studies of women managed using HPV genotypin g,p16an do theri mmunost ains, cytogenetics, andoth ermarke rs arene ededtog uidet heirincor- porationi ntomana ge mento fcervic alabn ormalities.
The effect of HPV vaccination on large cohorts overlong periods of follow-up remains to be studied, andwhether prior HPV vaccination alters natural history ormanagement of cytologic or histologic abnormalitiesremains unknown. Prospective study of the negativeconsequences of screening, diagnosis, and treatment areneeded to allow balancing of risks and benefits.
Outcomes analyses using the LAST Project’s two-tier squamous intraepi theli all esio ns(SIL)te rminologyare neededto directho wtran sla tion ofthree-t ierCINter- minology tothetwo -tier ter mino logycanbe madeand todefine howspeci ficma nag emen trecommen dations forhisto logicdia gnose sin thet wo-tiersy stemcanbe created( SeeBox2) .Inpa rti cula r,studies ofthesafety ofobserv ationfor young wom enwi thhistolo gicHSIL areneede d,asrepo rtsto dat ehav eincluded diagnostic excision asastudy endpo int .Est imatesofr egression andprogr essionra tesan dth epro portionof women whoevent uallyreq uiree xci sion areneeded .Long-term outcomes afterapp arent reg ress ionwithou ttreatment areunkno wn.
As the number and sophistication of tools applied to cer vicalc anc erpreventionco nt inuet oincrease, the co mpl exityo fma nagementpromis es togro w.Electroni c me dic alreco rds andbedsideandp oc ketco mputershold gr eat promis efo rassistingclin ic iansa ndpatients inne- got iating thi scomplexity.De ve lopme ntofrisksc oring th atinco rporatespa stscreen in gandtreat menthistory in to management decision sm ayhel ptobalancerisksand
Figure 18.
S22 & MAS SAD ET AL .
9.
9.
5.
9.
benefits on a more individualized level than consensusguidelines. Future consensus conferences will be neededto integrate new approaches.
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APPENDIX A: ADDITIONAL COAUTHOR PARTICIP AN TS,ACKNOWL EDGEDNONAUTHOR DELEGATE S, ANDPARTICI PATING ORGANIZA TI ONS SeeAppe n di x2,avai lab leon lineatht t p: //links .lw w.co m/ LGT/A10, fo rfinanc ial disc losurein formatio nf rom the c oaut hord elegates.
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; JuliaC.Ga ge, PhD,MP H; Francis coA. R.Ga rcia,M
D, MPH;Mohie dea nGhofr an i,MD,MB A;Ri char dS. Guido,MD; Eri cC.Hua ng ,MD,PhD ;Ver sieJ ohnso
n- Mallard,P hD, ARNP;E li zabethA .Kos tas- Polston,
P. Power,MD; Wal terPre nd iville, MD;D ebbi eSaslow, PhD;Kar enS hea,MS N, WHNP-BC ;Mar yK.S idawy, MD;Mari oSi deri, MD;KateSi mon, PhD;Silvio Tat ti ,MD;Je ffr eyWal dman,MD;Ja sonD .Wright, MD ; Fred Wyan d;a ndLaurie C.Zephyri n,M D,MPH,MBA N onaut horD eleg atesWhose Cont ributio nisAc-
knowledged:VickiB.Benard,PhD;NataliaComella,PhD; MariBethGagnon,MSCT(ASCP)HTL;AnnLaros, MD;MonaSaraiya,MD,MPH;ElizabethR.Unger,PhD, MD; andRose H. Xu,Pharm D,MS c. :AmericanAcademyof ParticipatingOrganizations F amilyPh ys icians;A meri can BoardofPat holo gy;
American Cancer Society; American College Health
S26 & MAS SAD ET AL .
Association; American College of Obstetricians andGynecologists; American Social Health Association;American Society for Colposcopy and Cervical Pathol-ogy; American Society for Cytopathology; Associationof Reproductive Health Professionals; CDC - Division ofCancer Prevention and Control; CDC - Division ofHigh-Consequence Pathogens and Pathology; CDC -Division of Laboratory Science & Standards; College ofAmerican Pathologists; Food & Drug Administration;International Federation for Cervical Pathology andColposcopy; International Gynecologic Cancer Society;National Cancer Institute; Nurse Practitioners inWomen’s Health; Planned Parenthood Federation ofAmerica; Society of Canadian Colposcopists; Society ofGynecologic Oncologists; Society of Obstetricians andGynaecologists of Canada; and Women Veterans HealthStrategic Healthcare Group.
APPENDIX B: DEFINITION OF TERMSColposcopy 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 e Adequ atecolp oscopy sq uam ocolumnarju nc tio nandthe margins ofanyvi s-
ible lesion can be visualized with the colposcope.
is assessment for cervical disease using a Co -testing co mbinationo fcy tologyan dHPVtes tinga tthesametime, 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 eoplasiausing either a colposcope or endocervical sampling.
Diagnostic excisional procedure is the process of ob-taining a specimen from the transformation zone andendocervical canal for histologic evaluation and includeslaser conization, cold-knifeconization, loop or needle elec-trosurgical excision, and loop electrosurgical conization.
are those that carry lower risk Les serab norm aliti es ofC IN3+t hano therr esult s.Theseincl udenegativecytology with either HPV-16 or HPV-18 or persistentuntyped oncogenic HPV, ASC-US, and LSIL.
HPV, human papillomavirus; CIN, cervical intra- epit helia lneoplasia;ASC- US,a typicals quamouscellsof unde termi nedsignificance ;LSI L,low-gr adesquamous intra epithelial lesions .
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