KANKER SERVIKS

(KANKER MULUT RAHIM-

LEHER RAHIM)
KANKER SERVIKS
 Anatomi Serviks
TAMPILAN LEHER RAHIM

NormalNormal Kanker Serviks

 KANKER ?

TUMOR
TUMOR JINAK TUMOR GANAS
KANKER

Misal : Mioma uteri

Misal : Kanker Leher rahim (serviks)
kanker indung telur (ovarium)
Kanker Badan Rahim ( endometrium)
The Enemy
Stadium Kanker Serviks
 Kanker Serviks di Dunia
No 2 di antara kanker pada perempuan,
Setiap 2 menit 1 meninggal akibat Kanker Serviks

75,000
36,000
266,000
143,000

72,000 79,000
33,000 62,000

Ferlay J et al. Globocan 2002, IARC 2004.

Incidence / year ≈ 500,000 Deaths / year ≈ 270,000

 Ten Most Common Cancers in Indonesia
(Pathological Anatomy Based Registry, 2008)
4000

3500

3000

2500

2000

1500 Series1

1000

500

0
 Epidemiology
10 Most Common Cancers in 10 Most Common Cancers in
Women in Jakarta Men in Jakarta

Skin 3.78% Soft Tissue 1.94%

Thyroid Gland 4.18% Liver 3.24%

Leukemia 4.42% Leukemia 4.55%

Corpus Uteri 7.19%

Types of Cancer

Lymph Nodes 4.85%

Types of Cancer
Nasopharyngeal 7.29% Skin 5.02%

Ovary 7.56% Renal Pelvic-Bladder 5.05%

Bronchus and Lung 7.65% Nasopharynx 7.93%

Colorectal 11.68% Colorectum 12.49%

Cervix Uteri 17.60% Prostate Gland 13.47%

Breast 31.10% Bronchus and Lung 19.63%

Hospital Based Data,

Ministry of Health Republic of Indonesia, 2007
Data
2004 - 2013
Dari Jakarta

2,47%

1.3/1000
Dari 342
Puskesmas
 Estimated 58 new cases of
Cervical cancer every day

30.400 cases per-year

2 years survival rate 80%

24.000 deaths in 2 year

12.000 deaths every year

33 cervical cancer patients

death
every day

Kusuma F, Jovian R, Pratiwi R, Purwoto G. Characteristic and survival rate of patient with advanced stage cervical cancer that
given adjuvant therapy in cipto mangunkusumo hospital, Jakarta. Poster session presented at: the 4 th Biennial meeting of
Asian society of gynecologic oncology; 2015 Nov 12-14; South Korea.
 RISIKO KANKER SERVIKS

Insidens infeksi HPV 3,5%

Insidens infeksi HPV risiko tinggi 77,3%
Risiko menderita kanker serviks pada HPV risk tinggi
positif 5-25 %

120 juta, 72 juta, 2 520 000, 1 947960

97 398 penderita kanker serviks
68 178 penderita stadium lanjut
63 penderita meninggal setiap hari
GEJALA

• Pendarahan pervaginam
• Keputihan bercampur darah, berbau
• Nyeri panggul
• Tidak dapat
buang air kecil
 PENYEBAB
KANKER SERVIKS
Human Papillomavirus (HPV)
Virus DNA , Ø 52-55 nm 100 tipe , ~30–40 menyerang anus dan kelamin2
HPV merupakan penyebab utama kanker serviks ~ 100%

Tipe penyebab kanker Tipe jinak

High risk group-16,18, Low risk group- 6,11.
31,33,45,52,58

HPV 6
HPV 16

HPV 18 HPV 11

• >75% kasus kanker serviks 5,6 90% kasus kutil kelamin5

• >50% kasus kanker Vaginal & Vulva5
1.Schiffman M, Castle PE. Arch Pathol Lab Med. 2003;127:930–934. 2. Wiley DJ, Douglas J, Beutner K, et al. Clin Infect Dis. 2002;35(suppl 2):S210–S224. 3. Muñoz N, Bosch FX, Castellsagué X, et al. Int J
Cancer. 2004;111:278–285. Reprinted from J Virol. 1994;68:4503–4505 with permission from the American Society for Microbiology Journals Department. 4. Walboomers JM, Jacobs MV, Manos MM, et al.
J Pathol. 1999;189:12–19. 5. X. Castellsagué, S. de Sanjose, T. Aguado, K. S. Louie, L. Bruni, J.Muñoz, M. Diaz, K. Irwin, M. Gacic, O. Beauvais, G. Albero, E. Ferrer, S. Byrne,F. X. Bosch. HPV and Cervical
Cancer in the World. 2007 Report. WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre). Available at: www.who.int/hpvcentre6. Bhatla N et al.Vaccine (2008;26; 2811-17
 Penyebab Kanker Serviks
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.
INFEKSI VIRUS HPV TIDAK DIIKUTI GEJALA
Sexual
Genital-genital
Manual genital
Oral genital
Kondom tdk
melindungi
Penularan ibu-bayi
JUMLAH SAMPLE : 20 000
INSIDEN INFEKSI HPV :

INSIDENS INFEKSI HPV ONKOGENIK :

 Kanker yang dapat disebabkan HPV
Kanker ~100%
Serviks1,
3
Kanker
45% penis3 Kanker ~40%
Vulva1

Kanker
mulut
12-70% tenggorok Kanker 60-90%
an3 Vagina1

~100%
Genital Kanker Female
Warts
3
1,
anus1-3 80+% Both sex
Male

Percentages represent cases atrributable to HPV infection

Braaten KP et al. Rev Obstet Gynecol. 2008;1:2–10.
• Hoots BE et al. Int J Cancer. 2009;124:2375–2383.
• IARC. IARC monographs on the evaluation of carcinogenic risks to humans. Human papillomaviruses. Vol 90. Lyon, France: IARC, 2007.
PERJALANAN PENYAKIT
KANKER SERVIKS
Cervical carcinogenesis
 PERJALANAN KANKER SERVIKS

INFEKSI HPV-RT SEROKONVERSI

7-8 TAHUN
INFEKSI
RATA-RATA KLASIK 15 TH
9 BULAN
AWAL
RESPON IMUN

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-infeksi
10-25%

DNA-ve DNA+ve PERSISTEN

INFEKSI BERULANG
8,9-14,8 months 4,5
2,3
VAKSINASI 4 TH

High grade lesion

SKRINING
2 TH

KANKER SERVIKS
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
 Pracancer Lesion Cancer

HPV ------------------- 3-17 year --------------------

Mild Carcinoma Cervical

Moderate Severe
Dysplasia Insitu Cancer
Dysplasia Dysplasia
(=Stage 0)

Screening !
 PECEGAHAN
KANKER SERVIKS
PENCEGAHAN PRIMER
PENCEGAHAN SEKUNDER
PENCEGAHAN TERSIER
 SCREENING
PAP IVA DNA-HPV

Disadvantage :
Sampling error
Fixation error
Processing error
Interpretation error
Kriteria adekuasi:
• Preparat utuh, tidak pecah LIMITATION
• Dilengkapi dengan label yang jelas LSIL, ASCUS,
• Informasi klinis yang informatif INCONCLUSIVE
• Jumlah sel yang adekuat, sekitar 8000-12.000 sel Sensitivity < 60%
• Mengandung sel skuamosa dan sel endoserviks
Pap’s Smear

Laboratorium
 SCREENING
PAP IVA DNA-HPV

National Screening Program 2015

Routine Gynecology Examination 2014 VIA
Easy, cheaper, effective
Available for rural and
urban

Disadvantage
Management abnormal VIA

Cryotherapy
LETZ, LEEP
 SCREENING
PAP IVA DNA-HPV
 SCREENING
PAP IVA DNA-HPV

GENOTYPING HC-2

HPV-16 Recommended by WHO as primary screening

HPV-18 cervical cancer

HPV-DNA
POSITIVE
Recently, the FDA approved the HPV-DNA test that can be
used as a stand-alone test without a Pap smear
 Tantangan Kesehatan Perempuan Indonesia
adalah KANKER SERVIKS

Kanker Serviks dapat Dicegah

1. Penyebab jelas – HPV

2. Perjalanan Penyakit –
ada tahap pra kanker serviks
3. Metode deteksi dini “Cost Effective”
4. ada Vaksin HPV
Kanker Serviks
INFEKSI HPV
 VLP

VAKSIN TIDAK MENGANDUNG VIRUS

VAKSIN BERISI BAGIAN KULIT VIRUS YG DIBUAT

ATAU SINTESISNYA
 Active protection via vaccination is mediated by neutralizing
antibodies at the cervix

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).
 Composition of HPV Vaccine
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
 Impact of 4vHPV Vaccine in Public
Vaccination Programs: Select Reportsa Genital Warts
Baandrup Ali Wilson Smith
Sex Transm Dis13 BMC Infect Dis16 Sex Transm J Infect Dis24
Infect20
Read
Sex Transm Leval
Infect8 J Infect *Blomberg Ali Chow *Droletc
Dis11 Clin Infect BMJ17 BMJ21 Lancet Infect
Dis14 Dis25
Fairley Donovan
Sex Transm Lancet
Flagg Harrison
Introduction of 4vHPV vaccine1–6 Infect7 Infect Dis9 Bauer
*Leval
Am J Public
*Petráš
JNCI3 PLoS One22 Vaccine26
Am J Health18
Public
Health12
Oliphant
Mikolajczyk Nsouli-Maktabi Liu *Dominiak-Felden
NZMJ10
Czech Republic Sex Transm MSMR19 Sex Transm PLoS One6
Dis15 Infect23

Cervical
Australia Abnormalities *Baldur-Felskov *Crowe *Smith
Cancer Causes BMJ31 Pediatrics33
*Gertig Control30
Brotherton *Powell BMC Med29
New
Canada Lancet27 Vaccine28
Zealand *Baldur-Felskov *Mahmud *Hariri *Herweijer
Sweden
JNCI4 J Clin Oncol32 Vaccine34 Int J
Cancer35
Belgium
United Denmarkb HPV Prevalence
States *Tabrizi Markowitz *Tabrizi Deleré *Dunne *Markowitz
J Infect J Infect Dis37 Lancet BMC Infect J Infect Pediatrics41
Germany Dis40
Dis36 Infect Dis38 Dis39

2006 2007 2008 2009 2011 2012 2013 2014 2015 2016
*Study links effectiveness data to vaccination statusaIncludes reports published in the peer-reviewed scientific literature, and does not encompass reports at scientific conferences. bBeginning on February 1,
2016 the childhood vaccination program includes the 2vHPV vaccine.42 cMeta-analysis of data from 20 studies in 9 countries (United States, Australia, England, Scotland, New Zealand, Sweden, Denmark,
Canada, and Germany), including both 4vHPV vaccine and 2vHPV vaccine.25
Please see corresponding slide note for references.
 Australia: Cervical Abnormalities
reduction

Australia: Population-based analysis of % reduction in cervical Australia: Population-based analysis of percentage reduction in
abnormalities among vaccinated (at least 1 dose) vs contemporaneous cervical abnormalities among vaccinated vs contemporaneous
unvaccinated screened females in Victoria unvaccinated screened females in Queensland
Garland et al; Impact and Effectiveness of the Quadrivalent Human Papillomavirus Vaccine: A Systematic Review of 10 Years of
Real-world Experience: CID, 2016
Canada & Denmark: Cervical Abnormalities
reduction

Canada: % reduction in cervical abnormalities in Denmark: %reduction in cervical abnormalities in females

vaccinated/vaccine era vs contemporaneous unvaccinated/ vaccinated with 4vHPV vaccine (≥1 dose) vs unvaccinated
prevaccine era in 3 provinces women by birth cohort
Garland et al; Impact and Effectiveness of the Quadrivalent Human Papillomavirus Vaccine: A Systematic Review of 10 Years of
Real-world Experience: CID, 2016
 Sweden & USA: Cervical Abnormalities
reduction

Sweden: % reduction in CIN2+ and CIN3+ among females fully United States: % reduction in HPV 16/18-related cervical
vaccinated with 4vHPV vaccine (3 doses) vs unvaccinated abnormalities among females vaccinated with 4vHPV vaccine (at
/partially vaccinated females, by age at first dose least 1 dose) vs contemporaneous unvaccinated females
Garland et al; Impact and Effectiveness of the Quadrivalent Human Papillomavirus Vaccine: A Systematic Review of 10 Years of
Real-world Experience: CID, 2016
HALAL
 Age at first marriage1 Pre-marital sex and aged of sexual
activity2
•Survey taken from 63.428 respondent aged 10-24
years. 86.7% of them haven’t been married2
•Among those who haven’t been married, 3% man
and 1.1% women said they already sexually active2

Proportion of
respondent aged
10-24 years who
haven’t been married
based on first age
sexually active 2

Percentage of women aged 10-59 years

based on age at first marriage1

1,2. Riskesdas 2010. Badan Penelitian dan Pengembangan Kesehatan,

Kemenkes RI
 Wanita usia 10 - 55 tahun
• Laki-laki usia 10 - 26 tahun
 Kanker Serviks
di Indonesia
 Kanker tersering di Indonesia
~ (34.4% dari kanker pada perempuan)1
 Hampir 70% sudah pd stadium
lanjut ( > stage IIB) 2,

 15.000 kasus baru, 8.000 kematian 3;

40 – 45 kasus baru,
20 – 25 meninggal dunia/hari,
1 orang meninggal/jam

 Cakupan Skrining < 5%

(ideal ~ 80%)

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 1992
3). IARC, Globocan 2002 database; Summary table by Cancer 2002. http://www-dep.iarc.fr/top.htm.Accessed Feb 1, 2007
PREVALENSI RESPONDEN YG PERNAH
DINYATAKAN KANKER SERVIKS 1,1%

PERNAH IVA

PREVALENSI IVA POSITIF

PERNAH PAP SMEAR

ALASAN TDK SKRINING (BELUM PERLU

43,4% ,TAKUT 8,7% , MALU 6%)
PENCEGAHAN KANKER SERVIKS