hpv testing in national cervical ca screen when is it recomended

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  • 7/27/2019 HPV Testing in National Cervical CA Screen When is It Recomended

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    Human papillomavirus testing in the Nati onal Cervical Screening Program when is it recommended?clinical

    ntrs th gnital skin thrgh micr-abrasins in

    th pithlim. Th virs is cntaind within th

    pithlim and ds nt cas viramia. Tpicall,

    HPV ntrs th basal clls and ss th hst cll

    rplicativ nzms t assmbl and rlas nw

    virins frm th pprmst clls f th sqams

    pithlim.3

    In sm cass, assciatd with th high risk

    HPV tps, th HPV gnm bcms intgratd

    int th hst chrmsm. In this frm, th

    infctin is mr likl t bcm prsistnt and

    clllar changs ccr that ma b rcgnisd as

    high grad changs n a Pap smar.

    High grade squamousintraepithelial lesions

    Crvical ctlg (th Pap smar) xamins

    xfliatd clls frm th crvix t dtct significant

    clllar changs assciatd with prsistnt HPVinfctin. Prsistnt infctin with n f th high

    risk HPV tps ma b sn as high grad changs

    r HSILs. Ths changs incld fatrs sch

    as a dns r dbl ncls, r a high nclar-

    ctplasmic rati.

    High grad changs ar rprtd at a rat f

    arnd 8.5 pr 1000 crvical ctlg tsts.4 This

    mans that arnd 21 000 Astralian wmn

    rciv a rprt f an HSIL ach ar.

    Data frm Astralian labratris sggst that

    wmn with HSIL ctlg rprts hav a 6289%

    chanc f harbring actal high grad crvical

    intrapithlial disas and a 03% chanc f

    having an invasiv crvical cancr.2 Thrfr,

    ndr th NHMRC gidlins wmn with a

    pssibl r dfinit HSIL dtctd n crvical

    ctlg shld b rfrrd fr clpscp.1

    A rviw f th litratr n th natral histr

    f CIN has shwn that wmn with histlgical

    vidnc f CIN 2 hav a 5% chanc f prgrssin

    t crvical cancr, and wmn with histlgical CIN

    3 hav a 12% chanc f prgrssin.5 It is thrfr

    rcmmndd that ths wmn b tratd inrdr t rdc thir risk f dvlping invasiv

    sqams cll crvical cancr. Tratmnt ma b

    ablativ r xcisinal.

    Development of cervicalcancer

    Thr ar fr main stps fr th dvlpmnt f

    crvical cancr:2

    infctin f th mtaplastic pithlim at th

    crvical transfrmatin zn (th sqam-

    clmnar nctin) with a high risk r ncgnic

    tp f HPV

    prsistnt infctin with an ncgnic HPV tp

    prgrssin f prsistntl infctd pithlim t

    pr-cancrs changs (HSILs), tpicall taking

    115 ars t bcm stablishd

    invasin thrgh th basmnt mmbran f th

    pithlim. Invasiv crvical cancr dvlps

    vr man ars. Rapid nst cancrs can ccr,

    bt th ar vr rar.

    Human papillomavirus testingpost-HSIL treatment

    Wmn tratd fr a bips-cnfirmd HSIL shld

    rtrn t thir spcialist fr rpat clpscp and

    crvical ctlg 46 mnths aftr tratmnt. If

    ths tsts ar satisfactr, thr is n rasn wh

    th wman shld nt rtrn t hr sal gnralpractitinr fr sbsqnt Pap tsts and HPV

    tsting.

    Tsting fr high risk HPV tps is an imprtant

    part f th managmnt f wmn wh hav

    bn tratd fr HSIL. Svral stdis hav shwn

    that ths wmn ar at incrasd risk f frthr

    high grad disas.611 Aftr tratmnt, th vast

    marit f wmn will clar thir ncgnic HPV

    infctin within 24 mnths (Figure 1).1218 Th

    rliabl ngativ prdictiv val f HPV tsting

    allws ths wmn t rtrn t th rtin Pap

    scrning intrval.

    When to perform HPVtesting

    Crvical ctlg and HPV tsting shld

    cmmnc 12 mnths aftr tratmnt f a bips-

    cnfirmd HSIL and cntin annall ntil th

    wman has tstd ngativ fr bth tsts n tw

    cnsctiv ccasins. At this pint th wman

    can thn rtrn t rglar pplatin scrning,

    accrding t th rcmmndatins fr th gnral

    fmal pplatin, which is crrntl tw-arl(Table 1). Mdicar cvrs tw HPV tsts in ths

    circmstancs in an nging 2 ar prid (MBS

    Itm nmbr 69418).

    Hman papillmavirs tsting bnd ths

    rcmmndatins is nt crrntl advisd (Table 2).

    If th GP is ncrtain f a patints mdical

    histr, stat crvical ctlg rgistris can sall

    prvid frthr infrmatin t gid sbsqnt

    tsting.

    Th frqnc f psitiv HPV tsts fllwing

    tratmnt fr a high grad lsin is high in th

    first 12 mnths aftr tratmnt, bt diminishs

    significantl aftr 12 mnths, as shwn in Figure 1.

    Figure 1 als dmnstrats th imprtanc f nttsting t sn aftr tratmnt.

    If HPV tsting is prfrmd tsid th NHMRC

    gidlins, pathlg labratris will sall

    charg abt $60100.

    How to perform HPV testing

    HPV tsting is sall prfrmd b taking a swab

    r brsh sampl frm th ndcrvix aftr crvical

    ctlg has bn takn. This is thn placd in

    a transprt tb (prvidd b r labratr) fr

    tsting. Th rsrcs listd at th nd f this

    articl prvid frthr dtails n sampl cllctin.

    If a liqid basd sampl is bing cllctd fr

    thr rasns, HPV tsting can b dn n this

    sampl.

    Diffrnt mthds fr tsting fr ncgnic

    HPV tps ar availabl; chck with r labratr

    fr thir rqirmnts. It is xtrml imprtant t

    mak sr that th tst ffrd has bn clinicall

    validatd.

    Th rslt shld b availabl at th sam tim

    as th crvical ctlg rprt.

    Clinical scenarios

    Jenna, 57 years of age, had treatment for a

    biopsy-confirmed HSIL in 1989. Since then

    she has returned conscientiously every 12

    months for a Pap test as she was originally

    told to do. Her smear results have been

    negative since treatment. What will your

    practice be when you next see her for her

    annual Pap test?

    0

    10

    20

    30

    40

    50

    3 months 12 months 24 months

    Per

    centofHPVp

    ositive

    tests

    Post-HSIL treatment intervals

    Figure 1. HPV infection rates by time

    since HSIL treatment

    464Rprintd frm AuSTRALIAN FAMILy PHySICIAN VoL. 42, No. 6, juNe 2013

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    clinicaHuman papillomavirus testing in the N ational Cervical Screening Program when is it recommended?

    smears have been negative, including

    a Pap test and HPV test 12 months ago.

    Today you take another Pap smear and

    an HPV test. The HPV test is negative,

    the Pap smear is also negative but has no

    endocervical cells present.

    on rviwing r rcrds fr Sall, nt that

    hav statd that saw th crvical s clarl

    and wr abl t insrt bth th ctbrsh

    and th swab/brsh fr th HPV tst int it. If this

    is th cas, th Pap smar ds nt hav t b

    rpatd. W knw that abt 12% f wmn vr

    th ag f 60 ars hav a transfrmatin zn

    that is prsmabl highr than th lngth f th

    ctbrsh.19 It is nt rcmmndd that th brsh is

    vr insrtd sch that th lwr bristls cannt b

    sn. Sall can nw rtrn t tw-arl scrning

    ntil th ag f 70 ars, at which pint, shld hr

    intrvning smars cntin t b ngativ, shcan cas having Pap tsts.

    Lesley, 38 years of age, had a high grade

    cervical lesion treated just under 2 years

    ago. She had her first Pap test and HPV

    test 12 months post-treatment: both tests

    were negative. She knows she has come in

    a little early for her repeat test (11 months

    after the last tests), but she is about to go

    overseas for 6 months and is keen to have

    the tests done before she goes. What will

    you do?

    Th first Pap tst and HPV DNA tsts mst b

    n arlir than 12 mnths aftr th high grad

    histlg rslt, bt th tim btwn frthr tsts

    and an prcding tst f ach tp (smar, HPV

    DNA) has t b at last 10 mnths.20 Thrfr

    it is qit clinicall accptabl t rpat Lsls

    tsts at this tim rathr than hav hr wait ntil h

    rtrn frm vrsas.

    Summary

    oncgnic HPV tsting is a rliabl and xtrml

    snsitiv tst that is Mdicar rbatabl whn sdin th managmnt f wmn wh hav vr had a

    histlgicall-cnfirmd HSIL tratd. Th apprpriat

    s f tsting fr th high risk, ncgnic, HPV tps

    is a valabl tl, as th vast marit f wmn in

    ths circmstancs will bcm ngativ fr ths

    ncgnic tps. This will nt nl b rassring

    fr ths wmn, bt will bring thm back int th

    rtin crvical scrning intrval.

    or challng is t ncrag its s.

    likl xplanatin fr this is that hr bd is still

    claring th virs. This prcss can tak a cpl f

    ars. Sh nds a rpat Pap tst and HPV tsting

    in 12 mnths.

    Martha, 43 years of age, presents to you for

    a Pap test. She has recently moved from

    interstate. She recalls that around 1998 she

    had a smear that showed some abnormal

    cells, and that she had treatment for these

    at that time. She has no idea what the

    biopsy actually showed. She has had two or

    three smears since then, which she believes

    were negative. What should you do?

    yr stat crvical ctlg rgistr will b abl

    t prvid th tlphn nmbr fr thr stat

    crvical ctlg rgistris. It is cnfirmd that

    in Ma 1997, Martha had a crvical bips that

    shwd a mild dsplasia (CIN 1); sh has had thr

    smars sinc thn, all f which hav bn ngativ.

    As Martha did nt hav a bips-cnfirmd

    high grad lsin sh is nt ligibl fr Mdicar

    rbatabl HPV tsting. Bfr th NHMRC

    gidlins (2005), lw grad (CIN 1; mild dsplasia)lsins wr ftn tratd. Tda st nd t

    d a Pap smar n Martha and rmind hr f th

    imprtanc f rglar rtin crvical scrning.

    Sally, 66 years of age, has a past history of

    a biopsy-confirmed high grade lesion when

    she was aged 36 years (in 1983). She has

    presented reasonably regularly over the

    years, and apart from a low grade smear

    (possible HPV) in 1993, all her other annual

    y can xplain t jnna that thr is nw a

    rliabl tst t chck fr th prsnc f th HPV

    tps that can cas crvical cancr. It is a vr

    snsitiv and accrat tst. Th vast marit f

    wmn, xplain t hr, clar this virs within a

    ar r tw f tratmnt. If, vn aftr sch a lng

    tim, this is fnd t b th cas with hr, n tw

    cnsctiv ccasins 12 mnths apart, sh will

    b abl t rtrn t 2-arl instad f annal Pap

    tsts. In ths circmstancs, th tst is ligibl fr

    th Mdicar rbat.

    Emily, 28 years of age, is seeing you 6

    months after she was reviewed by her

    gynaecologist post-treatment of a high

    grade cervical lesion (CIN 2) 12 months

    ago. The letter from the gynaecologist

    assures you that the Pap smear and

    colposcopy at 6 months were both normal.

    Emily is new to your practice and has a

    few questions about HPV that she feels

    have not been adequately answered.

    y xplain t emil that th crrntrcmmndatin is that sh hav a Pap tst and

    an HPV tst (t chck fr viral claranc) vr

    12 mnths ntil sh has a ngativ Pap tst

    and a ngativ HPV tst n ar, fllwd b

    a ngativ Pap tst and a ngativ HPV tst th

    fllwing ar. Aftr that sh can rtrn t th

    tw-arl intrval.

    Th rslts shw a ngativ Pap smar and a

    psitiv HPV tst. y can tll emil that th mst

    Table 1. HPV testing recommendations post-HSIL treatment

    Time since treatment Cervical cytology Coloposcopy HPV testing

    46 months

    12 months

    24 months

    Continue cervical cytology and HPV testing every 12 months until these tests areboth negative on two consecutive occasions

    The Medicare rebate for HPV testing in these circumstances covers two HPV tests inan ongoing 24 month period (item number 69418)

    Table 2. Current NHMRC guidelines for when HPV testing is not

    recommended1

    Less than 12 months after treatment of a high grade cervical lesion

    As a screening test

    As a triage tool for women with low grade squamous intra-epithelial cervical lesions(unless this is part of the follow up post-treatment of an HSIL)

    Rprintd frm AuSTRALIAN FAMILy PHySICIAN VoL. 42, No. 6, juNe 2013 465

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    Human papillomavirus testing in the Nati onal Cervical Screening Program when is it recommended?clinical

    Resources TakingaPaptest:instructionalDVD.Producedby

    Victrian Ctlg Srvic and Mlbrn Sxal

    Halth Cntr, and spprtd b PapScrn

    Victria. This DVD dmnstrats hw t tak an

    HPV tst (as wll as hw t tak a Pap smar).

    It is availabl fr f charg frm VCS Pathlg

    b calling 03 9250 0300. It can als b watchd

    nlin at www.mshc.rg.a. G t halth pr-fssinals thn vids

    Cervixsamplingcard.ThisA4-sizedlaminated

    card shws pictrs f diffrnt crvics, and

    dscribs th rcmmndd tchniqs and

    instrmnts that shld b sd whn taking a

    Pap tst. It als dscribs tsting fr HPV sing

    th Hbrid Captr brsh. Th card is fr f

    charg and is availabl frm PapScrn Victria

    at www.papscrn.rg.a

    HPV:Aguideforpractitioners.ThisA4-sized

    laminatd sht has a chck-list fr xplaining

    HPV t patints, as wll as th answrs t man

    cmmn qstins patints ask. It als givssm backgrnd n HPV fr mdical practitin-

    rs, xplains th prps f HPV tsting, tlins

    HPV tsting pst-HSIL tratmnt, and prvids

    cmmn scnaris with diffring rslts fr

    patints wh hav bn tratd fr an HSIL

    lsin. It is fr f charg frm PapScrn

    Victria at www.papscrn.rg.a.

    AuthorStlla Hl BA(Hns), MBBS, FAChSHM, is Snir

    Liaisn Phsician, Victrian Ctlg Srvic,

    Mlbrn, Victria. [email protected].

    Cmpting intrsts: Nn.

    Prvnanc and pr rviw: Nt cmmissind;

    xtrnall pr rviwd.

    References1. Natinal Halth and Mdical Rsarch Cncil.

    Scrning t prvnt crvical cancr. Gidlinsfr th managmnt f asmptmatic wmnwith scrn dtctd abnrmalitis. Canbrra:NHMRC, 2005.

    2. Schiffman M, Castl Pe, jrnima j, Rdrgz AC,Wachldr S. Hman papillmavirs and crvicalcancr. Lanct 2007;370:890907.

    3. Strn PL, Kitchnr HC, ditrs. Vaccins fr thprvntin f crvical cancr. oxfrd onclg Librar.oxfrd univrsit Prss, 2008.

    4. Astralian Institt f Halth and Wlfar. Crvicalscrning in Astralia 20092010. Cancr sris n67. Cat n. CAT 63. Canbrra: AIHW, 2012.

    5. ostr AG. Natral histr f crvical intrapithlialnplasia: a critical rviw. Intrnatinal jrnal fGnaclgical Pathlg 1993b;12:18692.

    6. Pttrssn F, Malkr B. Invasiv carcinma f thtrin crvix fllwing diagnsis and tratmnt f insit carcinma. Rcrd linkag std with a natinalcancr rgistr. Radithr oncl 1989;16:11520.

    7. Lvi F, Randimbisn L, La Vcchia and Francschi S.Incidnc f invasiv cancrs fllwing carcinma insit f th crvix. Br j Cancr 1996;74:13213.

    8. Sttr WP, d Barrs Lps A, Fltchr A, t al.Invasiv crvical cancr aftr cnsrvativ thrap frcrvical intrapithlial nplasia. Lanct 1997;349:97880.

    9. Nagai y, Mahama T, Asat T, Kanazawa K.Prsistnc f hman papillmavirs infctin aftrthraptic cnizatin fr CIN 3: is it an alarm frdisas rcrrnc? Gnacl oncl 2000;79:2949.

    10. Vikki M, Pkkala e, Hakama M. Risk f crvical cancr

    sbsqnt t a psitiv scrning ctlg; fllw-p std in Finland. Acta obstt Gncl Scand2000;79:5769.

    11. Mitchll H, Hcking j. Inflncs n risk f rcr-rnt high grad crvical abnrmalit. Int j GnaclCancr 2002;12:72834.

    12. Kcra e, Slitz G, Czrwnka K, BritnckrG, Ldltr S, Rinthallr A. Is high-risk hmanpapillmavirs infctin assciatd with crvicalintrapithlial nplasia liminatd aftr cnisatinb larg-lp xcisin f th transfrmatin zn? erj obstt Gncl Rprd Bil 2001;100:726.

    13. Nbbnhis MA, Mir Cj, van dn Brl Aj, tal. Additin f high-risk HPV tsting imprvs thcrrnt gidlins n fllw-p aftr tratmntfr crvical intrapithlial nplasia. Br j Cancr

    2001b;84:796801.14. Paraskvaidis e, Klipls G, Alamans y,

    Malam-Mitsi V, Llis eD, Kitchnr HC. Hmanpapillmavirs tsting and th tcm tratmntfr crvical intrapithlial nplasia. obstt Gncl2001;98(5 Pt 1):8336.

    15. Bar-Am A, Gamz R, Lvin I, Fainar o, Niv j, AlmgB. Fllw-p cmbind ctlg and hman papil-lmavirs tsting fr patints pst-cn bips:rslts f lng-trm fllw-p. Gnacl oncl2003;91:14953.

    16. Dbarg VH, Cllint P, Vinatir D, t al. Valf hman papillmavirs tsting aftr cnisatinb lp lctrsrgical xcisin fr high gradsqams intrapithlial lsins. Gnacl oncl2003;90:58792.

    17. Zilinski GD, Rzndaal L, Vrhrst Fj, t al. HPVtsting can rdc th nmbr f fllw-p visits inwmn tratd fr crvical intrapithlial nplasiagrad 3. Gnacl oncl 2003;9:6773.

    18. Cha Angl, Lin Chn-Ta, Hsh Swi, t al.usflnss f hman papillmavirs tsting inth fllw-p f patints with high grad crvicalintrapithlial nplasia aftr cnizatin. Am j obsttGncl 2004;190:104651.

    19. Mitchll H. Th ndcrvical cmpnnt f Papsmars. Lttr. Md j Ast 1994;161:396.

    20. Natinal Crvical Scrning Prgram. Minimmnatinal standards fr fllw-p and rmindr; prt-cls fr ctlg rgistrs. Dcmbr 2010. Availablat www.cancrscrning.gv.a/intrnt/scrning/

    pblishing.nsf/Cntnt/ctlg-rgistrs [Accssd7 jn 2013].

    466Rprintd frm AuSTRALIAN FAMILy PHySICIAN VoL. 42, No. 6, juNe 2013