Divisi Onkologi, Departemen Obstetri Ginekologi

Fakultas Kedokteran Universitas Indonesia

 HPV
(Human Papilloma Virus)

 99,7% Kanker Serviks disebabkan

oleh HPV onkogenik
(penyebab kanker).1

 HPV 16 &18 penyebab utama

70 % kanker serviks di dunia 2

1. Wallboomers JH et al. J Pathol 1999; 189: 129; 2. Bosch FX et al. J Clin Pathol 2002; 55: 244–65.
 Attributable Attributable to HPV
to HPV % all 16/18
HPV
Total cancer
Site % Cases % Cases
cancers
Cervix 492,800 100 492,800 93.5 70+ 344,900

Vulva, vagina 40,000 40* 16,000 3 80 12,800

Anus 15,900 90* 14,300 2.7 92 13,100
Oropharynx 9,600 12* 1,100 0.2 91 1,000
Mouth 98,400 3* 2,900 0.5 97 2,800
Total 527,100 374,600
Adapted from Parkin DM & Bray F. Vaccine 2006; 24(Suppl 3):S11–S25.
Walboomers JMM, et al. J Pathol 1999; 189:12–19.
 Courtesy of Dr. Andrijono SpOG (K) Onk

Most of cervical cancer cases came in

at late stage (stage IIIb)1

1. http://www.inasgo.com/webrscm/Laporan/Staging_Cervix.aspx (accessed on 3rd Aug 2010)

KANKER PENIS
 40 39 70 59
7 32
44 55 42
PCV1 18 27
13 45 61 2a
11 57
6
73 3
34 28
10
RhPV1 29
58
33 51
52 26 30
16
35 53
56
31 66

 The alpha-papillomavirus genus of the papillomavirus phylogenetic tree is

shown*
 Oncogenic types closely related to HPV 16 and 18 are highlighted
 HPV 16 is most closely related to HPV 31
 HPV 18 is most closely related to HPV 45
* Selected species and types are shown

Adapted from de Villiers E, et al. Virology 2004; 324:17–27.

• Ada 630 juta orang terinfeksi HPV di dunia
• Sebagian perempuan (80%) akan terinfeksi HPV pada usia 5)
tahun .2
• Infeksi HPV merupakan infeksi yang sering pada usia muda
18 sd 28 tahun.3
• HPV terbukti sebagai penyebab kanker serviks .4

1. WHO data. 2003. Available at: http://www.who.int/vaccines/en/hpvrd/shtml. Accessed July 12, 2004.
2. CDC Fact Sheet. May 2004.
3. Koutsky L. Epidemiology of Genital Human Papillomavirus Infection. Am J Med 1997;102:3-8. .
4. KL Wallin et al. New Engl J Med 1999;341(22)1633
CARA PENULARAN
HPV
JALUR SEKSUAL JALUR NON SEK SUAL

K ONTAK K E LAMIN DILUAR KELAMIN PENULARAN LANGSUNG

IBU HAMIL
● HUBUNGAN INTIM ● WC UMUM
● KELAMIN – KELAMIN ●PAKAIAN DALAM
● T
ANGAN – KELAMIN ●ALAT-ALA
T SAA
T PERSALINAN
KEDOKTERAN YANG ( MELAHIRKAN BA
YI )
● MULUT - KELAMIN TIDAK STERIL

TIMBUL KUTIL P
ADA
SALURAN PERNAP ASAN
BAYI
 Seroconversion
7-8 years
Infection First lesion
Immune response average time classically 15 ys
9 months

Sustained clinical
remission 8-30 M
9,8 months
75-90%
Incubation Active growth Host DNA-ve
(1–6 months) (3–6 months) containment
(3–6 months) Re-infection
10-25%

DNA-ve DNA+ve Persistent or

recurrent disease
8,9-14,8 months 4,5
2,3

4 yrs

High grade lesion

Natural history of cervical cancer
2 yrs

Invasive Cancer
Modified from Stanley M. Vaccine 2006;24S1:S1/16–22.
(2). Molden T, et al. Int J Cancer.2005:973-6. (3) Rozendaal L, etal. Int J Cancer 1996;68:766-9 (
4).Franco EL, etal. J Infect Dis 1999;180:1415-23. (5)Munoz N, etal. J Infect Dis 2004;190:234-42
 Lesi Pra Kanker Kanker

HPV Kanker 3-17

Vaksin Serviks
tahun
dapat
------------------- --------------------

DICEGAH!!

Displasia Displasia Displasia Karsinoma Kanker

Ringan Sedang Keras Insitu Serviks
Deteksi Dini
 NETWORK
Surveillanc
PENCEGAHAN PENCEGAHAN PENCEGAHAN e
PRIMAR SEKUNDER TERSIER • Cakupan
Pencegahan Skrining Terapi Skrining
Kontak Deteksi Dini & kanker, (70-80%)
karsinogen Terapi Prakanker rehabilitasi &
(HPV) at Ca invasif Dini Perawatan • Cakupan
palliative HPV Vaccine
• Pap-Smear
Promosi/ • Penurunan
• IVA
Edukasi Terapi Stadium
• Terapi
HPV Vaccine lanjut Kanker.
(al. Krioterapi)
Training: • Penurunan
• Health provider Kematian
Training Training
• PKK (Cadres)
• All women
 Mengandung kapsul protein kosong / virus-
like particle (VLP)  menggunakan teknologi
rekombinan
 Tidak mengandung produk biologis atau DNA
 tidak infeksius
 HPV
VAKSIN

Tidak dapat
masuk
Merangsang tubuh
membentuk Antibodi Antibodi
(kekebalan tubuh) terhadap (terbentuk)
HPV
SERVIKS
( LEHER RAHIM )
www.cegahkankerserviks.org
 HPV infects target cells in the basal
 HPV vaccination focuses on layer of the cervical epithelium
preventing HPV infection
through generation of high Infection

levels of ‘neutralizing’
antibodies Basal cell layer
of cervical

Neutralizing antibodies bind to

epithelium

HPV’s outer shell (capsid) and Neutralizing antibodies prevent HPV
prevent infection of host cells1 from infecting basal epithelial cells

Neutralizing antibodies are No infection

the likely mediator of

protection
WHO 20062

1. Stanley M, et al. Vaccine 2006; 24(Suppl 3):S106–S113;

2. WHO Expert Committee on Biological Standardization, 2006.
 HPV Neutralizing antibodies

Cervical canal

Cervical
epithelium

Blood vessel

Epithelial tear

Basement membrane

1. Stanley M. Vaccine 2006; 24:S16–S22;

2. Giannini S, et al. Vaccine 2006; 24:5937–5949;
3. Nardelli-Haefliger D, et al. J Natl Cancer Inst 2003; 95:1128–1137;
4. Poncelet S, et al. IPC 2007(poster).
 Cervarix™
Antigens AS04 adjuvant

+ Aluminium
salt
(Al(OH)3)
+ MPL
Immunostimulant

HPV 16 VLPs HPV 18 VLPs

AS04-containing vaccine

QUADRIVALENT
Antigens Adjuvant

+ Aluminium salt
(amorphous aluminium
hydroxyphosphate
sulphate [AAHS])
HPV 16 VLPs HPV 18 VLPs HPV 6 VLPs HPV 11 VLPs

AAHS-containing vaccine
Quadrivalent, 0-2-6
Bivalent, 0-1-6

9 – 13 years old : TWO DOSES

Suntikan : 0-6
Usia 9 – 13 tahun

Dua dosis

0, 6
  Vaksin bivalen
 PATRICIA Study (phase III trial)
 Efikasi 93,2% terhadap CIN 3+ (95% CI 78,9 – 98,7)
 Vaksin kuadrivalen
 Phase II trial, follow-up 3 tahun
 Efikasi 99% terhadap CIN 2/3 yang berhubungan
dengan HPV 6/11/16/18 (95% CI 92 – 100)

• Harper DM, Franco EL, Wheeler CM, Moscicki AB, Romanowski B, Roteli- Martins CM, et al. Sustained efficacy up to 4.5 years of a bivalent L1
virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 2006;367:1247-55.
• http://www.fda.gov/ohrms/dockets/ac/06/slides/2006-4222s-index.htm, FDA presentation, slides 31 and 48.
 INDONESIAN HPV VACCINE GUIDELINE

PROPHYLACTIC VACCINE

IM DELTOID MUSCLE 10-55 YEARS OLD

0,1,6
0, 6
SEXUAL (-)
LACTATION
HPV VACCINE
SEXUAL (+)
NO PREGNANCY PAP SMEAR (-)

PRECANCER LESION HPV INFECTION

IN THE PAST IN THE PAST

NO HPV INFECTION NO PRECANCER LESION

VACCINATION + PAP SMEAR
POGI (HOGI)-IDAI
Quick Reduction of Genital Wart Incidence as Early Marker to
Evaluate Successfulness of HPV Vaccination Program

Experience from HPV Vaccination Program in Australia

Significant Decrease of Genital Wart Incidence in Women (1-4 years after HPV Quadrivalent
Vaccination Program)
*Vaccination for girls and women 12-26 years old

20 qHPV vaccine 34,900 females

introduced <21 Years (n=9,405)
Genital Wart Diagnosis (%)

18
21–30 Years (n=15,228)
16
>30 Years (n=10,246)
14 Prevaccine period Vaccination period
12

10

4 –72.6%
Ptrend <0.001
2
Ptrend <0.001 –92.6%
0
2004 2005 2006 2007 2008 2009 2010 2011

Year
qHPV=quadrivalent human papillomavirus.
Figure reproduced from BMJ, Ali H et al, 346, f2032, 2013, with permission from BMJ Publishing Group Ltd.
1. Ali H et al. BMJ. 2013;346:f2032.
 25%↓

51%↓

Brotherton JML et al; Human papillomavirus vaccination is changing the epidemiology of high-grade cervical lesions in Australia; Cancer causes and control. 2015:
http://download-v2.springer.com/static/pdf/838/art%253A10.1007%252Fs10552-015-0568-6.pdf?token2=exp=1429004490~acl=%2Fstatic%2Fpdf%2F838%2Fart%25253A10.1007%25252Fs10552-
015-0568-6.pdf*~hmac=14ca126e7bea23b351998da45355fadf20c2fc346893818c42e62c6f93502eaf
 PROGRAM PENANGGULANGAN KANKER SERVIKS
PROGRAM VAKSINASI NASIONAL
PR USIA 12 TH (10-13 TH)
DUA DOSIS
VAKSINASI NASIONAL/PROP
DAERAH BINAAN
PENGADAAN VAKSIN TERJANGKAU
VAKSINASI MANDIRI
VAKSINASI PR >14 TAHUN (BELUM
MENIKAH/ YG SUDAH MENIKAH)
SEKOLAH, PERGURUAN TINGGI,
PERUSAHAAN,
SEKTOR PRIVATE
PROGRAM SKRINING (IVA)
PEREMPUAN YAMG SUDAH MENIKAH
(PROGRAM IBU PRESIDEN)
PENINGKATAN CAKUPAN SKRINING IVA
MANAJEMEN IVA ABNORMAL
MANAJEMEN KANKER SERVIKS
EDUKASI
KURIKULUM DOKTER, BIDAN
KADER
SISTEM RUJUKAN
VAKSIN QUADRIVALENT