deteksi dini kanker serviks / kanker mulut rahim terkini
DESCRIPTION
fie ini merupakan materi seminar kesehatan reproduksi di STIKES Kepanjen pada 21 Juli 2009.TRANSCRIPT
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Deteksi Dini Deteksi Dini &&
Pencegahan Kanker MulutPencegahan Kanker MulutRahim TerkiniRahim Terkini
Dr. dr. Imam Rasjidi, Dr. dr. Imam Rasjidi, SpOG(K)Onk SpOG(K)Onk
Disampaikan di STIKES Kepanjen, Malang 21 Juli 2009
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Dr. dr. Imam Rasjidi, SpOG (K) Onk lahir di Surabaya tahun 1960Dr. dr. Imam Rasjidi, SpOG (K) Onk lahir di Surabaya tahun 1960Tahun 1986Tahun 1986 lulus dokter di FK Unair Surabayaulus dokter di FK Unair SurabayaTahun 1990-1995 pendidikan Spesialisasi Obstetri Ginekologi UnairTahun 1990-1995 pendidikan Spesialisasi Obstetri Ginekologi UnairTahun 2000-2004 pendidikan konsultan Onkologi Ginekologi FK-UITahun 2000-2004 pendidikan konsultan Onkologi Ginekologi FK-UITahun 2000Tahun 2000 pendidikan Displasia dan Onkologi di Royale Women pendidikan Displasia dan Onkologi di Royale Women Hospital Melbourne AustraliaHospital Melbourne AustraliaTahun 2008 Doktor FKM- UITahun 2008 Doktor FKM- UIDosen Obstetri Ginekologi di Fakultas Kedokteran Universitas Brawijaya Dosen Obstetri Ginekologi di Fakultas Kedokteran Universitas Brawijaya Malang dan Universitas Pelita Harapan, Tangerang. Malang dan Universitas Pelita Harapan, Tangerang. Direktur Pusat Studi Reproduksi dan Kesehatan WanitaDirektur Pusat Studi Reproduksi dan Kesehatan Wanita
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490,000 perempuan didiagnosa*
menderita kanker serviks
240,000 di antaranya MENINGGAL
Menurut WHO Menurut WHO TIAP TAHUN, DI SELURUH DUNIA:TIAP TAHUN, DI SELURUH DUNIA:
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Kanker Serviks di IndonesiaKanker Serviks di Indonesia
Kanker yang paling sering di Indonesia ~ (34.4% dari kanker pada wanita)1
Hampir 70% datang dengan stadium lanjut 2, sehingga angka survival rendah
15.000 kasus baru, 8.000 kematian3; Perhari ~40 kasus baru, Perhari ~20 kematian Perjam ~1 kematian
1).Dirjen Pelayanan Medik Departemen Kesehatan RI. Badan Registrasi Kanker IAPI, Yayasan Kanker Indonesia. Kanker di Indonesia Tahun1998. Data Histopatologik.2). Mochtarom M. Data registrasi Kanker Ginekologik. Bagian Obstetri dan Ginekologi.RSUPN /FKUI, Jakarta 19923). IARC, Globocan 2002 database; Summary table by Cancer 2002. http://www-dep.iarc.fr/top.htm.Accessed Feb 1, 2007
Seluruh dunia Setiap 1 menit 1 kasus baruSetiap 2 menit 1 kematian
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KANKER SERVIKS DISEBABKAN OLEH HUMAN PAPILLOMAVIRUSa,1,2
120 Tipe HPV telah diketahui120 Tipe HPV telah diketahui30-40 Tipe HPV menyerang anogenital30-40 Tipe HPV menyerang anogenital
Low risk type ( HPV 6 & 11 )Low risk type ( HPV 6 & 11 )(tidak menyebabkan kanker)(tidak menyebabkan kanker)Menyebakan anogenital wartsMenyebakan anogenital warts
High risk type ( HPV 16 & 18)High risk type ( HPV 16 & 18)Menyebabkan kanker serviksMenyebabkan kanker serviks
Infeksi dengan HPV seringkali TIDAK menimbulkan gejala Infeksi dengan HPV seringkali TIDAK menimbulkan gejala Banyak orang TIDAK tahu mereka terinfeksi HPVBanyak orang TIDAK tahu mereka terinfeksi HPVBanyak orang dapat menularkan HPV TANPA menyadarinyaBanyak orang dapat menularkan HPV TANPA menyadarinya
Anogenital : area kelamin (termasuk kulit penis, Anogenital : area kelamin (termasuk kulit penis, mulut vagina & anus)mulut vagina & anus)
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Menurut WHO ada hubungan yang erat antara Kanker serviks dan HPV (Human Papilloma Virus) 99%
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Jika Anda terinfkesi HPV
80% akan dibersihkan dengan sistem immun (kekebalan)
10- 20% berkemungkinan menjadi infeksi persisten (menetap)
Resiko menjadi kanker serviks
Kebanyakan pria dan wanita yang telah berhubungan intim, beresiko terinfeksi HPV
Lebih dari 75% wanita yg berhubungan intim, pernah terinfeksi HPV, puncak di antara umur 18-22 tahun
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Angka kejadian HPV di Amerika Serikat makin meningkat75% wanita yang secara seksual aktif terpapar HPVPrevalensi HPV usia 13-20 tahun 40%Mahasiswi 43%
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Sering kambuh Beban psikologis bagi penderitanya Tingkat kesembuhan bervariasi4
Disebabkan HPV tipe 6 & 11.
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Berganti-gantiPasangan seksual
Usia hub sex <20 tahun
merokok
Sistem imun menurun
Ibu & saudara perempuan
Riwayat papsmear sblmnya abNPenyakit menular seksual
Faktor RisikoKanker Leher Rahim :
terkena kanker leher rahim
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WANITA YANG MEMPUNYAI RISIKO MENDAPAT KANKER LEHER RAHIM
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Resiko Relatif CA Cervix dari Beberapa Faktor
Faktor RisikoFaktor Risiko Risiko relatifRisiko relatif
Usia pertama hubungan seks (tahun)Usia pertama hubungan seks (tahun) < 16< 16 16 – 1916 – 19 > 19> 19
16163311
Jarak antara hubungan seks pertama dengan menarche (tahun)Jarak antara hubungan seks pertama dengan menarche (tahun) < 1< 1 1 – 51 – 5 6 – 106 – 10 > 10> 10
2626773311
Jumlah pasangan seksJumlah pasangan seks > 4 pasangan (dibandingkan 0 atau 1 pasangan)> 4 pasangan (dibandingkan 0 atau 1 pasangan) 3,63,6
Jumlah pasangan seks sebelum usia 20 tahunJumlah pasangan seks sebelum usia 20 tahun > 1 pasangan (dibandingkan tanpa pasangan)> 1 pasangan (dibandingkan tanpa pasangan) 77
Genital wartsGenital warts Ada (dibandingkan tidak ada)Ada (dibandingkan tidak ada) 3,23,2
Merokok > 5 batang perhariMerokok > 5 batang perhari Selama > 20 tahun (dibandingkan < 1 tahun)Selama > 20 tahun (dibandingkan < 1 tahun) 4404/12/23
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PERJALANAN PENYAKITPERJALANAN PENYAKIT
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Perjalanan alamiah penyakit Kanker Leher Rahim
Displasia Ringan
Displasia Sedang
Displasia Keras
Karsinoma Insitu
Kanker Serviks
Lesi Pra Kanker Kanker
SKRINING ! Deteksi Dini
------------------- 3-17 tahun -----------------------
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Serviks Normal (Leher Rahim)
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Lesi Pra Kanker
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Kanker Serviks
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Progresivitas dari CIN
RegressRegress PersistPersist Progress to CISProgress to CISProgress to Progress to
InvasionInvasion
CIN 1CIN 1 57%57% 32%32% 11%11% 1%1%
CIN 2CIN 2 43%43% 35%35% 22%22% 5%5%
CIN 3CIN 3 32%32% <56%<56% ---- >12%>12%
64 studies, 274 carcinomas, 15,473 CIN cases64 studies, 274 carcinomas, 15,473 CIN casesFollow-up <1-12 yearsFollow-up <1-12 years
Dikutip dari: Ostor, Int J Gyne Path 1993 12:186-19204/12/23
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MODALITAS DETEKSI DINI
KANKER SERVIKS
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Papsmear & IVA
Deteksi Dini
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Deteksi Dini Kanker Serviks/ Pencegahan Sekunder
• Tes skrining
• Tes pelengkap
• Tes diagnostik
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TES SKRINING
Tes Pap Konvensional
Papnet (skrining dibantu komputer)
Thinprep (liquid base, thin layer cytology)
IVA (Inspeksi Visual dengan Asam Asetat)
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TES PELENGKAP
ServikografiTes HPV-DNA
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TES DIAGNOSTIKKOLPOSKOPIKOLPOSKOPI
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Pap SmearPap Smear
Pemeriksaan sitologi eksfoliatif
dari epitel serviks untuk mendeteksi
lesi prakanker secara dini
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1. Usapan spatula Eyre pada ektoserviks dulu, Pulas di kaca benda
2. Usapan “Cytobrush” pada endoserviks, Pulas di kaca benda
3. Rendam kaca benda dalam alkohol 96%, minimal 30’
1).
2).
Tes PAP
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Cara Pengambilan Pap Smear
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Padanan dari klasifikasiPadanan dari klasifikasi
Class IClass I Class IIClass II Class IIIClass III Class IVClass IV Class VClass V
NormalNormal InflamInflamMildMild ModMod SevSev
CISCISCancerCancer
D y s p l a s i aD y s p l a s i a
NormalNormal AtypiaAtypiaCIN ICIN I CIN IICIN II
CIN IIICIN III CancerCancerK o i l o c y t o s K o i l o c y t o s i si s
WNLWNL
BenignBenign
CellularCellular
ChangeChangess
ASAS
CUSCUSLGSILLGSIL HGSILHGSIL HGSILHGSIL CarcinomCarcinom
aa
NEGATIFNEGATIFASAS
CUSCUSLGSILLGSIL HGSILHGSIL HGSILHGSIL CarcinomCarcinom
aa
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Inspeksi Visual dengan Asam Asetat (IVA)
Melihat serviks untuk mendeteksi abnormalitas setelah pemakaian asam asetat
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Asam asetat 3-5% Epitel serviks abnormal
Perubahan osmotik
Ekstrasel hipertonik
Membran kolaps
DNA
Epitel acetowhiteCahaya
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Penanggulangan Kanker serviks di indonesia
Setelah dipulas Asam Asetat 3 – 5%
IVA Non –invasif Mudah— murah di Puskesmas Hasil LANGSUNG Sensitivitas, spesifisitas
Memadai untuk negara di sarana terbatas
Provider IVA:•Bidan
•Perawat terlatih
•Dokter umum
•Dokter spesialis
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Sensitivitas, Spesifisitas?Studi Skrining Temuan IVA (1)
First AuthorFirst Author CountryCountryNu. ofNu. ofwomenwomen
Senstv.Senstv.SpecificitSpecificit
yyLevel ofLevel of
ProviderProviderGrade ofGrade of
Dis Dis DetectedDetected
Ottaviano et.al Ottaviano et.al
(2001) 8(2001) 8ItalyItaly 24002400 Colposcopist Colposcopist
postgrad trainpostgrad trainCIN I-II and CIN I-II and more severemore severe
Belinson et al.Belinson et al.
JHPIEGO JHPIEGO (1999) 9(1999) 9
ChinaChina 1,9971,997 71%71% 74%74% GynecologicGynecologic
OncologistOncologistCIN II and CIN II and
more severemore severe
Univ.of Univ.of ZimbabweZimbabwe
JHPIEGO JHPIEGO
ZimbabweZimbabwe 2,2032,203 77%77% 64%64% Nurse Nurse MidwifeMidwife
HSIL and HSIL and more severemore severe
Denny et al.Denny et al.
(2000) 10(2000) 10S.AfricaS.Africa 2,9442,944 58,%58,% 83,%83,% NurseNurse HSIL and HSIL and
More severeMore severe
Denny et al. Denny et al. (2002) 11(2002) 11
S.AfricaS.Africa 2,7542,754 58,3%58,3% 83,5%83,5% NurseNurse HSIL and HSIL and More severeMore severe
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STUDI IVA di INDONESIAAuthorAuthor CityCity NumbeNumbe
r r Sn Sn (%)(%)
SpSp
(%)(%)ProviderProvider Length of Length of
TrainingTraining
SjamsuddinSjamsuddin
(1995)(1995)JakartaJakarta 1,5441,544 76,976,9 95,295,2 GynecologistGynecologist Not Not
informedinformed
A.Zainul SalehA.Zainul Saleh
(2000(2000PalembanPalemban
gg208208 100100 12.812.8 Gynecologist/Gynecologist/
GPGPNot Not
informedinformed
Sastrowardoyo Sastrowardoyo AA
(2000)(2000)
SamarindSamarindaa
152152 5757 8484 MidwifeMidwife 2 days2 days
Gandamihardja Gandamihardja SS
(2002)(2002)
BandungBandung 215215 8787 95.595.5 Gynecologist/Gynecologist/GPGP
Not Not informedinformed
Hanafi I/Hanafi I/
Ocviyanti DOcviyanti D
(2001)(2001)
JakartaJakarta 1.0121.012 (95,4) (95,4) ??
(86,7) (86,7) ??
MidwifeMidwife 2 days +2 days +
guidingguiding
Nuranna LNuranna L
(2005)(2005)PademangPademang
an -an -JakartaJakarta
3,1963,196 98,298,2 98,998,9 MidfiweMidfiwe 2 days +2 days +
guidingguiding
Female CaFemale Ca
Program(2005)Program(2005)JakartaJakarta 4,3044,304
On going On going researchresearch
GP, MidwifeGP, Midwife 2 weeks2 weeks
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LAPORAN KEGIATAN BAKTI SOSIAL DALAM RANGKA HUT RI KE 60PEMERIKSAAN IVA DAN USG
TANGGAL TANGGAL 1/8/20051/8/2005 2/8/20052/8/2005 3/8/20053/8/2005 4/8/20054/8/2005 5/8/20055/8/2005 6/8/20056/8/2005 TOTALTOTAL
Total KunjTotal Kunj 1717 1717 1515 3131 1010 2727 117117
IV positifIV positif 33 22 11 22 22 11 1111
Pap’testPap’test 00 22 00 00 00 11 33
Radang/Radang/infksiinfksi
44 44 44 55 55 66 2828
KolposkopiKolposkopi 33 22 11 33 22 11 1212
USGUSG 1010 1010 66 1010 33 33 4242
Positif kanker 1.Ny. N( bagian gizi ) → Displasia sedang dengan Metaplasia Epitil yang Atypia (stadium 0)2.Ny. H ( bagian kebidanan) → Well Differentiatit Epidermoid Carcinoma Cervixs Uteri 3.Ny. S ( bagian OK ) → Carcinoma Endometrium ( stadium II) 04/12/23
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S afety
aa cceptability cceptability
FF easibility easibility
EE ffectiveness ffectiveness
IVA?
Metode skrining di IndonesiaMetode skrining di Indonesia
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Inspeksi visualisasi dengan aplikasi Inspeksi visualisasi dengan aplikasi asam asetat (IVA)asam asetat (IVA)
Meja ginekologi / tempat tidur
Lampu sorot
Spekulum
Asam asetat 3-5%
Kapas lidi 04/12/23
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• Langkah langkah pemeriksaan IVA
Pasien berbaring dalam posisi litotomiDi pasang spekulum cocor bebek yang kering tanpa pelumasSumber cahaya dari belakang lampu sorot 100 watt, diarahkan kedalam lubang vagina sehingga serviks tampak jelas terlihatPemeriksaan harus dapat menampakkan sambungan skuamokolumnar lama dan baru dimana daerah di antaranya disebut daerah transformasiJika hasil inspekulo dicurigai terdapat infeksi pada serviks, maka pasien harus terapi terlebih dahulu dan diperiksa ulang satu minggu kemudianDiambil sedian sitologi dengan prosedur standar, yaitu Mengusap permukaan tumpul spatula ayre, dan kanalis
servikalis dengan cytobrush Keduanya dihapuskan diatas kaca obyek yang telah di beri
nomor sitologi Kemudian di fiksasi dalam botol alkohol 95% selama 30
menit Dikeringkan dalam udara terbuka dan diberi nama serta
nomor urut
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Setelah selesai mengambil sediaan sitologi, dilakukan pemeriksaan IVA dengan cara membasahi permukaan serviks dengan asam asetat 3%, selanjutnya sengan mata telanjang dilihat perubahan yang terjadi pada serviks :
Normal : jika tidak terdapat bercak putih pada daerah transformasi (tes IVA negatif)
Atifik : jika terdapat bercak putih pada daerah transformasi (tes IVA positif)
Pengambilan sediaan sitologi dan pemeriksaan IVA harus dilakukan oleh orang yang samaHasil temuan IVA dicatat pada status pasienSediaan sitologi dikirim ke laboratorium sitologiPada kasus dimana pemeriksaan IVA positif, pasien dirujuk untuk kolposkopiPada kasus dimana hasil sediaan sitologi abnormal, pasien dirujuk untuk kolposkopi
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NORMAL
OVULA NABOTI
EKTOPI SERVIKS
I
II
TAMPILAN I V A
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III.LESI PRA KANKER
Lesi intra epitel serviks derajat rendah ~ NIS I
TAMPILAN I V A
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IV.KANKER SERVIKSInvasif
TAMPILAN I V A
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Skrining kanker serviksSkrining kanker serviks
KolposkopiKolposkopi
Visualisasi epitel dan perubahan vaskuler vagina dan serviks.
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KOLPOSKOPI
KOLPOSKOPIKOLPOSKOPI
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Visualisasi daerah transformasiVisualisasi daerah transformasi Visualisasi lesiVisualisasi lesi Biopsi lebih terarahBiopsi lebih terarah
Keuntungan :Keuntungan :
Kerugian :Kerugian : Peralatan mahalPeralatan mahal Membutuhkan pendidikanMembutuhkan pendidikan Kurang spesifikKurang spesifik
Skrining kanker serviksSkrining kanker serviks
KolposkopiKolposkopi
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Kolposkopi (4/9/06) : Lesi derajat tinggi. Dilakukan LEEP
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Skrining Kanker ServiksTes DNA HPV
Metode molekuler untuk menentukan tipe Metode molekuler untuk menentukan tipe HPV risiko tinggi. HPV risiko tinggi.
Spesifikasi lebih rendah dari tes Pap .Spesifikasi lebih rendah dari tes Pap .Manfaat pada wanita usia > 35 tahun.Manfaat pada wanita usia > 35 tahun.
Biaya mahal.Biaya mahal.
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Tes HPV
HPV sulit dikultur
Tes deteksi dan tipe HPV
3 tes
Hybrid Capture 2 ( HC2)
Polymerase Chain Reaction (PCR)
In Situ Hybridization (ISH)
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Tipe HPVTipe HPV
Ada 2 tipe HPV Risiko rendah, Risiko Tinggi
• Risiko Rendah– 6, 11, 42, 43, 44
• Risiko Tinggi– 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68
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AutoCYTEPAP NET
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Hasil Skrining PAP NET dengan AutoCyte
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PAP NET
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Hasil PAP NET setelah di baca oleh Ahli Sitologi
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PAP NET
• Pap Net meningkatkan akurasi skrining apusan serviks dengan mengurangi angka negatif palsu.
• Reskrining Pap Net dari hasil negatif skrining manual didapatkan 4,8 % abnormal. (Ferenczy,dkk. 1996)
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Kelebihan Pap Net Menurunkan angka negatif palsu dan positif palsu. Meningkatkan akurasi pemeriksaan Tes Pap. Menurunkan angka kesalahan skrining. Menurunkan waktu pemeriksaan skrining Tes Pap. Mengurangi angka kelelahan skrining. Jumlah sampel yang diperiksa dapat dalam jumlah besar.
Kekurangan Pap Net Harga mahal dan tidak ekonomis. Masih memerlukan tenaga ahli sitologi untuk menegakkan
diagnosis.
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THIN PREP LIQUID BASED CERVICAL CYTOLOGY
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Thin Prep
Preparasi sediaan Tes Pap dengan teknik Thin-Layer dimana hasil smear dapatberupa satu lapisan sel-sel tidak bertumpukdan tidak tertutup oleh darah, mukus, atau debris lainnya dengan.
Tujuan Thin Prep
Untuk meningkatkan akurasi hasil Tes Pap.
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Pap konvensional Thin prep
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A S C U S
Thin prepPap konvensional
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Kelebihan Thin Prep
• Menurunkan angka negati palsu dan positif palsu• Menurunkan angka Kesalahan interpretasi• Meningkatkan akurasi Tes Pap• Mengurangi kelelahan skriner
Kekurangan Thin Prep• Harga mahal
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Lesi Prakanker
• Disebut: Lesi Intraepitel (Cervical Intraepithelial Neoplasia)
• Awal perubahan menuju karsinoma serviks uteri
• Diawali NIS I NIS II NIS III
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Claficatio of Histopatological Findings
Di kutip dari:Frappart, et al. Histopathology and Cytopathology of the Uterine Cervix. Digital Atlas, Lyon, France: IARC Press, 2004.
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CIN as Seen In Colposcopy
Di kutip dari:Wright TC Jr, Cox JT, Massad LS, et al, for the ASCCP-Sponsored Consensus Congress.JAMA. 2002;287:2120–2129.
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Terapi Pengobatan Infeksi HPV
Dikutip dari : Prendiville W, Davies P, eds. The Health Professional’s HPV Handbook. 1: Human Papillomavirus and Cervical Cancer. London, UK: Taylor & Francis; 2004.
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INOVASIPILOT PROJEK PENAPISAN KANKER
LEHER RAHIM & PAYUDARA
• Tujuan : menemukan lesi pra kanker leher rahim & benjolan pd payudara• Sasaran : perempuan usia 30 – 50 thn• Cakupan: 80% dari sasaran pd lokasi pilot projek dlm 5 thn• Lokasi : - 2007: 6 Kab (Deli serdang, Gowa, Karawang, G. Kidul, Kebumen, Gresik). Masing-masing 4 PKM kecamatan.
- 2008: 6 Kab (Deli serdang, Gowa, Karawang, G. Kidul, Kebumen, Gresik,) Replikasi Kabupaten (Malang, Pekalongan).
Masing-masing 4 PKM kecamatan pengembangan.
• Metode : Kunjungan tunggal (single visit approach) dg IVA + Krioterapi & CBE + rujuk• Pelaksana: dokter, bidan pkm (terlatih)• Supervisor: 1. Klinis (dokter Obsgyn & Bedah) 2. Dinkes Kab dan Prop04/12/23
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Mengapa “Single Visit Approach?”
• Aman, mudah dilakukan dan tidak mahalAman, mudah dilakukan dan tidak mahal• Bisa dipelajari oleh semua ahli Bisa dipelajari oleh semua ahli
medis/tenaga kesehatanmedis/tenaga kesehatan• Semua perlengkapan dan peralatan Semua perlengkapan dan peralatan
tersedia di tempattersedia di tempat• Hasil deteksi dapat segera tersedia & dpt Hasil deteksi dapat segera tersedia & dpt
segera memberi pengobatan rawat jalan segera memberi pengobatan rawat jalan sehingga mengurangi opportunity losssehingga mengurangi opportunity loss
• Cocok untuk tempat dengan sarana yang Cocok untuk tempat dengan sarana yang paling minimpaling minim
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11 Langkah SINGLE VISIT APPROACH
Langkah 1 – KonselingLangkah 2 – Pemeriksan payudara klinisLangkah 3 – Pemeriksaan leher rahim dengan SpekulumLangkah 4 – Oleskan Asam Asetat 3-5 % pada ServiksLangkah 5 – Setelah 1 menit, periksa adanya lesi putihLangkah 6 – Diskusikan hasilnya dengan ibu.
Tawarkan pilihan pengobatan bila hasil positif
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Langkah 7 – Pemeriksaan spekulum untuk melihat ulang serviksLangkah 8 – Pasang Cryoprobe dan bekukan (freeze) selama 3 mntLangkah 9 – Defrost selama 5 menitLangkah 10 - Bekukan kembali (Re-freeze) selama 3 menitLangkah 11 – Pasca pengobatan dan petunjuk tindak lanjut
11 Langkah SINGLE VISIT APPROACH (lanjutan)
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VAKSINASI HPV PENCEGAHAN PRIMER PADA
KANKER MULUT RAHIM
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Pneumococcal Disease
HIV
Influenza
HibHPV
Rotavirus
Hepatitis A
Hepatitis B
Polio
Tuberculosis
Cholera
Malaria
Smallpox
Rabies
DiphtheriaPertussis
Tetanus
Yellow FeverMeaslesMumps
RubellaVaricella Zoster
Virus
ANCAMAN
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Variola (Cacar)
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Edward Jenner
Bapak Vaksinasi modern Pertama kali berhasil melakukan vaksinasi small pox
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Vaccine Milestones
• 1796 Edward Jenner mengembangkan vaksin smallpox
• 1885 Pasteur mengembangkan vaksin rabies
• 1955 Vaksin polio (injeksi) diperkenalkan • 1962 Vaksin polio (Oral/ tetes)
diperkenalkan• 1979 Smallpox sudah tereradikasi
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Vaccines through time…Vaccine-preventable disease by year of vaccine development or licensure—United States, 1798–1995
Note: The list is not exhaustive
World Health Organization: http://www.who.int/vaccines-diseases/history/ history.shtml [Accessed September 16, 2002].
Centers for Disease Control and Prevention: MMWR 48(12):243248, April 2, 1999.
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Vaksin Bivalent (Human Papiloma Virus tipe 16 &
18) &
Quadrivalent HPV (Human Papiloma Virus tipe 6, 11,
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Quadrivalent and Bivalent Vaccine Components
QuadrivalentQuadrivalent Bivalent VaccineBivalent Vaccine22
HPV typesHPV types
Doses in Doses in μμgg 20/40/40/2020/40/40/20 20/2020/20
Technology used Technology used to produce L1 to produce L1 VLPsVLPs
YeastYeastProprietary Proprietary
assembly/reassembly process assembly/reassembly process increasing stabilityincreasing stability
Insect cell Insect cell substratesubstrate
AdjuvantAdjuvantAmorphous aluminium Amorphous aluminium
hydroxyphosphate sulfatehydroxyphosphate sulfate
(Merck and Co., Inc.)(Merck and Co., Inc.)
AS04:AS04:
Aluminium hydroxide Aluminium hydroxide + 3-deacylated + 3-deacylated
monophosphoryl lipid Amonophosphoryl lipid A
(MPL, Corixa/GSK)(MPL, Corixa/GSK)
Adjuvant doseAdjuvant dose 225 225 μμgg 500 500 μμg/50 g/50 μμgg
1. Villa LL, Costa RLR, Petta CA, et al. Lancet Oncol. 2005;6:671–678.2. Harper DM, Franco EL, Wheeler C, et al. Lancet. 2004;364:1757–1765.
6 11 16 18 16 18
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Perkembangan vaksin HPV dimulai dengan… kurang lebih 15 tahun yang lalu
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Vaksin HPVVaksin HPV
• 4 HPV tipe 6, 11, 16, 18 (Quadrivalent)4 HPV tipe 6, 11, 16, 18 (Quadrivalent)• Vaksin recombinan (tidak mengandung virus Vaksin recombinan (tidak mengandung virus
hidup)hidup)• Dibuat melalui ragi (Dibuat melalui ragi (SaccharomycesSaccharomyces cerevisiae) cerevisiae)• Pemberian injeksi intra muscular Pemberian injeksi intra muscular • Dosis 0.5 cc Dosis 0.5 cc • Jadwal pemberian 0-, 2-, 6- bulan Jadwal pemberian 0-, 2-, 6- bulan
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89L1 VLPs Mimic the HPV VirionL1 VLPs Mimic the HPV Virion11––44
Viral DNA
Infectious HPVNoninfectious HPV VLP
Capsid proteins:L1
L2
Lacks viral DNA
LacksL2 protein
1. Stanley M. Vaccine. 2006;24(Suppl 1):S16–S22.2. Berzofsky JA, et al. J Clin Invest. 2004;114:450–462.3. Baker TS, et al. Biophys J. 1991;60:1445–1456. 4. Chen XS, et al. Mol Cell. 2000;5:557–567.
Structure of Human Papiloma Virus and Structure of Human Papiloma Virus and HPV vaksin HPV vaksin
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Cara Kerja VaksinCara Kerja Vaksin
Vaksin Vaksin
Merangsang Antibodi Merangsang Antibodi respon kekebalan tubuh respon kekebalan tubuh
terhadap HPVterhadap HPV
HPVHPV
ServiksServiks(Leher Rahim(Leher Rahim))
Antibodi Antibodi
AB menempel pada virus
Mas
uk
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Immune Response to HPV Vaccine:Immune Response to HPV Vaccine:A Proposed MechanismA Proposed Mechanism11––44
1. Stanley M. Vaccine. 2006;24(Suppl 1):S16–S22.2. Batista FD, et al. EMBO J. 2000;19:513–520.3. Tyring SK. Curr Ther Res Clin Exp. 2000;61:584–596.4. Chen XS, et al. Mol Cell. 2000;5:557–567.
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Ilustrasi Cara Kerja VaksinIlustrasi Cara Kerja Vaksin
HPV HPV HPV ditangkap HPV ditangkap
AntibodyAntibody
HPV tidak dapat masukHPV tidak dapat masuk Ke dalam sel serviks Ke dalam sel serviks
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Neutralizing Antibodies Correlate With Neutralizing Antibodies Correlate With Prevention of HPV InfectionPrevention of HPV Infection
Neutralizing antibodies prevent HPV infection
Nonneutralizing antibodies do not prevent infection
No antibodies— viral infection
Chen XS, et al. Molecular Cell. 2000;5:557–567.
Cell surface receptors
Antibody color legend:Blue = Neutralizing antibodiesYellow = Nonneutralizing antibodies
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Antibody Response to Antibody Response to QuadrivalentQuadrivalent is is DurableDurable11
Ph II–P007 Dose-Ranging 16- to 23-year-old womenPh II–P007 Dose-Ranging 16- to 23-year-old women
Long-term Persistence of Anti-HPV 16 cLIA Responses*
10,00010,000
10001000
100100
1010
00 2 32 3 6 76 7 1212 1818 2424 3030 3636 5454 6060 6161
60+160+1weekweek
QuadrivalentQuadrivalent n=78n=78
Placebo (Sero (-) and PCR (-))Placebo (Sero (-) and PCR (-))n=70 n=70
Anti-
HPV
resp
onse
Anti-
HPV
resp
onse
(GM
T le
vels
with
95%
CI
(GM
T le
vels
with
95%
CI
[log
[log 1010
sca
le])
sca
le])
Vaccination on day 0, at 2 and 6 months, and at 60 monthsVaccination on day 0, at 2 and 6 months, and at 60 months
Anti-human papillomavirus (HPV) 16 responses in 16- to 23-year-old females through 5 years of follow-up
MonthsMonths
*In subjects naïve to the relevant HPV type from day 1 through month 60.1. Data on file, MSD.04/12/23
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Guideline and Recommendation
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HPV Vote – Routine Vaccination
• ACIP recommends routine vaccination for females 11-12 years of age with three doses of Quadrivalent
• The vaccination series can be started as young as 9 years of age at the discretion of the provider
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HPV Vote – Vaccination of Females 13-26
• Vaccination is recommended for females 13-26 years of age who have not been previously vaccinated
• Ideally vaccine should be administered before sexual activity, but females who are sexually active should still be vaccinated
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– Cervical cancer screening – no change• Vaccinated females could subsequently be infected
with non-vaccines HPV types• Sexually active females could have been infected prior
to vaccination
– Decision to vaccinate should not be based on Pap testing, HPV DNA or HPV serologic testing
HPV Other Recommendations and Wording
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HPV Special Situations
• Equivocal or Abnormal Pap Test• Vaccination recommended; however
– Could already have been infected with a vaccine HPV type– Data do not indicate vaccine will have therapeutic effect on
existing cervical lesions or HPV infection
• Positive HPV test• Vaccination recommended; however
– Could already have been infected with a vaccine HPV type– Data do not indicate vaccine will have therapeutic effect on
existing cervical lesions or HPV infection
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HPV Special Situations• Genital Warts• Vaccination recommended; however
– Data do not indicate vaccine will have therapeutic effect on existing genital warts or HPV infection
• Immunosuppression• Can be vaccinated
– Not a live vaccine– Immune response and vaccine efficacy might be less than in
immunocompetent persons
• Lactating women• Lactating women can receive vaccines
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HPV Vaccination During Pregnancy Moved to Special Situations from Precautions and
Contraindications • Pregnancy*• Initiation of the vaccine series should be delayed until after
completion of the pregnancy• If a woman is found to be pregnant after initiating the
vaccination series, completion should be delayed until after the pregnancy
• If a vaccine dose has been administered during pregnancy, there is no indication for intervention
• * ACIP is creating working group to address vaccination during pregnancy specifically for all new vaccines
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Penting untuk di-INGAT!!!
• Kanker serviks adalah kanker yang banyak menyebabkan kematian pada perempuan
• Kanker serviks dapat dicegah :
– Deteksi sedini mungkin dengan PAP SMEAR
– Edukasi mengenai kanker serviks
– Vaksinasi HPV VAKSIN
American Cancer Detailed Guide. American Cancer Society Online Publication. http://www.cancer.org
KONSULTASIKAN KEPADA DOKTER ANDA KONSULTASIKAN KEPADA DOKTER ANDA TENTANG KANKER SERVIKS & CARA PENCEGAHANNYATENTANG KANKER SERVIKS & CARA PENCEGAHANNYA
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Small pox (cacar) sudah tereliminasi
Mungkin langkah selanjutnya Mungkin langkah selanjutnya
Kanker Serviks…?????Kanker Serviks…?????
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Mulailah Hari IniLangkah Pertama Membantu Cegah
Kanker Serviks!!!04/12/23