Vacina contra Papilomavírus humano (HPV): Promessas e ...· Promessas e Desafios . Sumário ......

download Vacina contra Papilomavírus humano (HPV): Promessas e ...· Promessas e Desafios . Sumário ... Risco

of 33

  • date post

    08-Nov-2018
  • Category

    Documents

  • view

    213
  • download

    0

Embed Size (px)

Transcript of Vacina contra Papilomavírus humano (HPV): Promessas e ...· Promessas e Desafios . Sumário ......

  • Edson D. Moreira Jr., MD, PhDEdson D. Moreira Jr., MD, PhDCentro de Centro de PesquisasPesquisas GonGonaloalo MonizMoniz

    FIOCRUZ FIOCRUZ -- BahiaBahia

    Vacina contra Vacina contra PapilomavPapilomavrusrus humano (HPV):humano (HPV):Promessas e Desafios Promessas e Desafios

  • SumSumriorio

    BiologiaBiologia do HPVdo HPV

    EpidemiologiaEpidemiologia e e ImpactoImpacto dasdas DoenDoenasas porpor HPVHPV

    Racional de Vacina contra HPVRacional de Vacina contra HPV

    VacinasVacinas contra HPVcontra HPV

    EficEficcia e Segurancia e Seguranaa

    Promessas e DesafiosPromessas e Desafios

  • BiologiaBiologia do HPVdo HPV

    >100 >100 tipostipos identificadosidentificados22

    ~30~304040 anogenitalanogenital2,32,3

    ~15~152020 oncognicosoncognicos,,2,32,3HPV 16 e 18 (HPV 16 e 18 (cncercncer do colo)do colo)44

    NoNo--oncognicosoncognicosHPV 6 e 11 (HPV 6 e 11 (verrugasverrugas genitais)genitais)33

    1. 1. Howley PM, Lowy DR. In: Knipe DM, Howley PM, eds. Philadelphia, Howley PM, Lowy DR. In: Knipe DM, Howley PM, eds. Philadelphia, Pa: LippincottPa: Lippincott--Raven; 2001:2197Raven; 2001:21972229. 2229. 2. Schiffman M, Castle PE. 2. Schiffman M, Castle PE. Arch Pathol Lab MedArch Pathol Lab Med. 2003;127:930. 2003;127:930934. 3. Wiley DJ, Douglas J, Beutner K, et al. 934. 3. Wiley DJ, Douglas J, Beutner K, et al. Clin Infect DisClin Infect Dis. . 2002;35(suppl 2):S2102002;35(suppl 2):S210S224. 4. MuS224. 4. Muoz N, Bosch FX, Castellsaguoz N, Bosch FX, Castellsagu X, et al. X, et al. Int J CancerInt J Cancer. 2004;111:278. 2004;111:278285. 285.

    VVrusrus DNA DNA dada famfamlialiaPapillomaviridaePapillomaviridae11

  • VerrugasVerrugas CutneasCutneasHPV tipo: 1,3 e 5HPV tipo: 1,3 e 5

  • VerrugasVerrugas nana CavidadeCavidade OralOralHPV tipo: 13 e 32HPV tipo: 13 e 32

  • VerrugasVerrugas GenitaisGenitaisHPV tipo: 6 e 11HPV tipo: 6 e 11

  • Diversidade de HPVs

  • Diversidade de HPVs

  • Diversidade de HPVs

  • Diversidade de HPVs

  • MecanismosMecanismos de de TransmissoTransmisso e e AquisioAquisio do HPVdo HPV ContatoContato SexualSexual

    AtravsAtravs de de relaorelao sexualsexual11

    GenitalGenitalgenital, manualgenital, manualgenital, oralgenital, oralgenitalgenital2244

    UsoUso de de preservativopreservativo podepode reduzirreduzir o o riscorisco, , masmas nono protegeprotegetotalmente.totalmente.22

    Via Via NoNo--sexual sexual MeMe parapara RN (RN (transmissotransmisso vertical)vertical)55

    FmitesFmites (e.g., (e.g., luvasluvas, , instrumentosinstrumentos cirrgicos)cirrgicos)6,76,7

    HipteseHiptese nono muitomuito bembem documentadadocumentada; ; raroraro

    1. Kjaer SK, Chackerian B, van den Brule AJ, et al. Cancer Epidemiol Biomarkers Prev. 2001;10:101106. 2. Winer RL, Lee S-K, Hughes JP, Adam DE, Kiviat NB, Koutsky LA. Am J Epidemiol. 2003;157:218226. 3. Fairley CK, Gay NJ, Forbes A, Abramson M, Garland SM. Epidemiol Infect. 1995;115:169176. 4. Herrero R, Castellsagu X, Pawlita M, et al. J Natl Cancer Inst. 2003;95:17721783. 5. Smith EM, Ritchie JM, Yankowitz J, et al. Sex Transm Dis. 2004;31:5762. 6. Ferenczy A, Bergeron C, Richart RM. Obstet Gynecol. 1989;74:950954. 7. Roden RB, Lowy DR, Schiller JT. J Infect Dis. 1997;176:10761079.

  • InfecoInfeco pelopelo HPV e HPV e AlteraesAlteraes no no EpitlioEpitlioCervical Cervical CausadasCausadas porpor estesestes VrusVrus

    *NIC = *NIC = neoplasianeoplasia intraepitelialintraepitelial cervical cervical

    AdaptadoAdaptado de Goodman A, Wilbur DC. de Goodman A, Wilbur DC. N Engl J MedN Engl J Med. 2003;349:1555. 2003;349:1555151564. 64.

    ColoColoNormal Normal

    InfecoInfeco porpor HPV/HPV/NIC* 1NIC* 1

    NIC 2 / NIC 3 /NIC 2 / NIC 3 /CncerCncer CervicalCervical

  • RiscoRisco de de InfecoInfeco porpor HPV HPV apsapsIncioIncio dada AtividadeAtividade SexualSexual

    1. Collins S, Mazloomzadeh S, Winter H, et al. 1. Collins S, Mazloomzadeh S, Winter H, et al. BJOGBJOG. 2002;109:96. 2002;109:9698. 2. 98. 2. Adapted from Winer RL, Lee SAdapted from Winer RL, Lee S--K, Hughes JP, Adam DE, K, Hughes JP, Adam DE, Kiviat NB, Koutsky LA. Genital human papillomavirus infection: IKiviat NB, Koutsky LA. Genital human papillomavirus infection: Incidence and risk factors in a cohort of female university studencidence and risk factors in a cohort of female university students. nts. Am J Epidemiol.Am J Epidemiol. 2003;157:2182003;157:218226, by permission of Oxford University Press.226, by permission of Oxford University Press.

    Adolescentes do sexo feminino(UK, 1988-1992)1

    Estudantes universitrias do sexofemino (US, 1990-2000) 2

    N=242N=242

    00

    1010

    4040

    5050

    7070

    6060

    3030

    2020

    Cum

    ulat

    ive

    Ris

    k of

    HP

    V In

    fect

    ion

    (%)

    Cum

    ulat

    ive

    Ris

    k of

    HP

    V In

    fect

    ion

    (%)

    Months Since First IntercourseMonths Since First Intercourse

    3636 4545 60602424121200

    Adapted from Collins, et al.Adapted from Collins, et al.

    N=603N=603

    00

    2020

    4040

    6060

    7070

    00Cum

    ulat

    ive

    Ris

    k of

    HP

    V In

    fect

    ion

    (%)

    Cum

    ulat

    ive

    Ris

    k of

    HP

    V In

    fect

    ion

    (%)

    Months Since First IntercourseMonths Since First Intercourse

    44 88 1212 1616 2020 2424 2828 3232 3636 4040 4444 4848 5252 5656

    Adapted from Adapted from WinerWiner, et al., et al.

  • EstimativaEstimativa AnualAnual dada IncidnciaIncidncia de de DoenDoenasas e e DiagnDiagnsticossticos relacionadosrelacionados aoao HPVHPV

    1. World Health Organization. Geneva, Switzerland: World Health 1. World Health Organization. Geneva, Switzerland: World Health Organization; 2003:1Organization; 2003:174. 2. World Health Organization. 74. 2. World Health Organization. Geneva, Switzerland: World Health Organization; 1999:1Geneva, Switzerland: World Health Organization; 1999:122. 322. 3. World Health Organization. Feature. 1990;152:1. World Health Organization. Feature. 1990;152:16 .6 .

    VerrugasVerrugas GenitaisGenitais: : 30 milhes30 milhes33

    InfecInfeceses porpor HPV HPV semsemanormalidadesanormalidades citolcitolgicasgicas

    detectdetectveisveis: : 300 milhes300 milhes22

    CncerCncer cervical: 0,5 milhocervical: 0,5 milho11

    LesesLeses cervicaiscervicais de alto de alto graugrau: : 10 milhes10 milhes22

    LesesLeses cervicaiscervicais de de baixobaixo graugrau: : 30 milhes30 milhes22

    AtribuAtribuveisveis a a tipostipos de de HPV de altoHPV de alto--riscorisco

    AtribuAtribuveisveis a a tipostipos de de HPV de HPV de baixobaixo--riscorisco

  • VerrugasVerrugas genitaisgenitais: : tratamentotratamento difdifcilcil e doloroso (e doloroso (recorrnciasrecorrncias soso comunscomuns) ) IncidnciaIncidncia crescentecrescente

    Verrugas Genitais Externas:Verrugas Genitais Externas:EpidemiologiaEpidemiologia

    1. Maw RD, et al. Int J STD AIDS. 1998;9:571578. 2. Kodner CM, Nasraty S. Am Fam Physician. 2004;70:23352342. 3. Franco EL et al. In: Franco E, Monsonego J. New Developments in Cervical Screening and Prevention. Oxford: Blackwell Science, 1997:1422. 4. Tortolero-Luna G. Hematol Oncol ClinNorth Am. 1999;13 :245257. 5. CDR Weekly. 2001;11(35).

    1972

    1974

    1976

    1978

    1980

    1982

    1984

    1986

    1988

    1990

    1992

    1994

    1996

    1998

    2000R

    ates

    of G

    enita

    l War

    ts D

    iagn

    oses

    (E

    ngla

    nd a

    nd W

    ales

    )5

    0

    50

    100

    150

    200

    250

    300

    Rat

    e pe

    r 10

    0,00

    0Males

    Females

  • IncidnciaIncidncia e e DistribuioDistribuio dasdas NeoplasiasNeoplasiasAssociadasAssociadas aoao HPVHPV

    HPV cases

    Total cases

    Cervix

    Oropharnyx

    Anus

    Oral cavity

    Larynx

    Vulva

    Penis

    Annual number of cases

    0 100,000 200,000 300,000 400,000 500,000

    * 11% * 11% cancercancer nas mulheres so causados p/ HPVnas mulheres so causados p/ HPV

  • RiscoRisco de de infecinfecoo pelopelo HPV HPV emem adultosadultos sexualmentesexualmente ativosativos 50% 50%

    HPV HPV umauma causacausa essencialessencial do cancer cervical do cancer cervical

    ProporProporoo atribuatribudada ~99.7%*~99.7%*

    ExameExame citolcitolgicogico preventivopreventivo tem tem restrirestrieses significativassignificativas

    TesteTeste necessnecessriorio durantedurante todatoda vidavida ((adernciaaderncia podepode ser ser difdifcilcil))

    SensibilidadeSensibilidade e e especificidadeespecificidade limitadaslimitadas

    NoNo previneprevine infecinfecoo pelopelo HPV (e as HPV (e as alteraalteraeses histolhistolgicasgicas relacionadasrelacionadas))

    Alto Alto custocusto

    VacinaVacina contra HPVcontra HPVRacionalRacional

    * * WalboomersWalboomers JM, et al.JM, et al. J J PatholPathol. 1999. 1999. .

  • CandidatoCandidato a a VacinaVacina contra HPVcontra HPVVLPsVLPs ((VirusVirus--like Particleslike Particles))

    ProteProtenana L1 do L1 do capscapsdeodeo do HPV do HPV um um antantgenogenoimportanteimportante no no mecanismomecanismo de de infecinfecoo

    CapsmeroCapsmero L1L1(~280 (~280 kDkD))

    5 x L15 x L1

    ProtenaProtena L1L1(55(5557 57 kDkD))

    VLPsVLPs(~20,000 (~20,000 kDkD))

    72 x Cap. L172 x Cap. L1

    EstaEsta proteprotenana capazcapaz de se autode se auto--arrumararrumar formandoformandopartpartculasculas semel