KANKER LEHER RAHIM

Indra Yuliati, dr, SpOG (K)

Divisi Onkologi Ginekologi
Dept/SMF. Obstetri dan Ginekologi
RSUD Dr.Soetomo/ FK UNAIR
Gambaran Visual Serviks Normal dan
Kanker Serviks

Serviks Normal Kanker Serviks

Apa Penyebab Kanker Leher Rahim ?
 Penyebab Kanker Serviks
HPV
• 99,7% Kanker Serviks disebabkan oleh
HPV onkogenik (penyebab kanker).1

• HPV 16 &18 merupakan penyebab utama

pada 70 % kasus 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.
 Human Papilloma Virus
Nonenveloped double-
stranded DNA virus1
• >100 types identified2
• ~30–40 anogenital2,3
– Oncogenic*,2,3 ~15–20
• HPV 16 and HPV 18 types
account for the majority of
worldwide cervical
cancers.4
– Nononcogenic** types
• HPV 6 and 11 are most
often associated with
dysplasia and external
anogenital warts.3
*High risk; ** Low
risk
1. Howley PM, Lowy DR. In: Knipe DM, Howley PM, eds. Philadelphia, Pa: Lippincott-Raven; 2001:2197–2229.
2. Schiffman M, Castle PE. Arch Pathol Lab Med. 2003;127:930–934. 3. Wiley DJ, Douglas J, Beutner K, et al. Clin Infect Dis.
2002;35(suppl 2):S210–S224. 4. Muñoz N, Bosch FX, Castellsagué X, et al. Int J Cancer. 2004;111:278–285.
NON-ONCOGENIC HPV
 GENITAL WART
ANOGENITAL

ORAL CAVITY WART RESPITATORY TRACT

SKIN
 Insidensi Kutil Kelamin di Indonesia

Terjadi peningkatan insidensi kutil kelamin 1

Saat ini kutil kelamin merupakan penyakit IMS

tertinggi di Indonesia.

Data courtesy of DR.dr.Wresti Indriatmi, Sp,KK

ONCOGENIC HPV
Gambaran Visual Serviks Normal dan
Kanker Serviks

Serviks Normal Kanker Serviks

 CANCER

HPV-16,18,52,31,45 ANAL INTRAEPHITELIAL

NEOPLASIA
ANAL
CERVIX,
VU,VA 90%,
HPV-16

HPV- 40-50%
PENILE
ORAL 0-47% 16,6,11 HPV-16/18

OROPHA 29.4-
RYNX 81.6%
12% HPV-16/1

0-8.5% HPV BREAST

6.3% HPV TONSILITIS
APMIS.2010;118:494-509
Cara Penularan
Beberapa faktor mempermudah infeksi HPV

• Usia muda (puncak infeksi usia 20–29 )1

• Berganti pasangan2
• Memulai hubungan di usia muda*,3
• Merokok*,4
• dll

*Findings not consistent across studies

 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

 Kelompok perempuan yang sudah
menikah (BPS, 2010)

Kel. Usia Jumlah Kel. Jumlah Kel. Usia Jumlah

Usia
10-14 53.732 35-39 8.815.871 60-64 3.083.941

15-19 1.460.516 40-44 7.969.925 65-69 2.438.188

20-24 5.853.756 45-49 6.856.121

25-29 9.089.962 50-54 5.797.265 Total:

64.681.633
30-34 9.283.254 55-59 3.979.102
NATURAL HISTORY of CERVICAL
CANCER
Sumber :
http://medicinembbs
Nat Rev Cancer, 2007
 SEROKONVERSI
7-8 TAHUN
INFEKSI INFEKSI RATA-RATA KLASIK 15 TH
AWAL 9 BULAN
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

4 TH

High grade lesion

PERJALANAN KANKER SERVIKS
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
 Tahapan pertumbuhan kanker
serviks

Infeksi Infeksi
Lesi Pertumbuhan
virus HPV
prakanker sel kanker
HPV persisten
 Bagaimana terjadinya Kanker Serviks ?

Sel Normal Lesi Pra Kanker Kanker

 Kanker Serviks
Onko Human Papiloma Virus (HPV)
protein type 16, 18 (70 %) infection
E6, E7

Pre Cancer Cancer

------------------- 3-17 years-----------
--------------

Mild displasia Moderate Severe Carcinoma Invasive

displasia Displasia
CIN I CIN II CIN III

Screening
 DETEKSI DINI
KANKER LEHER RAHIM
 Pap Liquid HPV
IVA Smear
Based
Genotyping
Colposcopy
Cytology
ANATOMI SERVIKS
1. APA itu IVA ???
I V A (Inspeksi Visual dgn Asam Asetat)
= pemeriksaan yang dilakukan (dokter/bidan/ paramedis) dgn
mengamati serviks yang telah diberi asam asetat / asam cuka 3-5%
secara inspeculo dan dilihat dengan penglihatan mata langsung (
mata telanjang). Pertama kali diperkenalkan Hinselman (1925).
 MEKANISME IVA
 Asam asetat meningkatkan osmolaritas cairan ekstraseluler 
menarik cairan intraseluler membran collaps dan jarak antarsel
akan semakin dekat
 Meningkatnya protein inti sel dan cytokeratine epitel serviks
 Sinar ke epitel tidak diteruskan ke stroma, tapi dipantulkan sehingga
permukaan epitel berwarna putih.
TEKNIK IVA
• Informed Consent.
• Litotomi
• Visualisasi yg Baik
• Observasi Kelainan
Genitalia Eksterna
• Spekulum
• Bersihkan Serviks
• Observasi Kel Serviks
• Asam Asetat (3-5%)
• Tunggu 1 Menit Inspeksi
Acetowhite
CARA MEMBUAT ASAM ASETAT
 TEKNIK IVA
Posisi litotomi,
tampilkan serviks, nilai:

4 langkah
1. Mencurigakan kanker,
tidak perlu IVA
2. SSK tampak seluruhnya?
(Jika tidak  IVA, beri
catatan, sebaiknya  tes
Pap)
3. Lakukan IVA  tunggu 1
menit, timbul epitel putih?
 IVA (+)
4. Kandidat krioterapi ?

KaSIVO
Dokumentasi dengan Kamera Digital

Sebelum asam asetat Setelah asam asetat

Dokumentasi dengan Kamera Digital

Sebelum asam asetat Setelah asam asetat

INSPEKSI VISUAL ASETAT
 Perbandingan skrining tes Pap dan IVA
Uraian/ Metode Skrining Tes PAP IVA
Petugas kesehatan Sample takers Bidan
(Bidan/perawat/dokter Perawat
umum/dr. spesialis) Dokter umum
↓ ↑ Dr. Spesialis
Skrinners/Sitologis/
Patologis
Sensitivitas 70% - 80% 65% - 96%

Spesifisitas 90% - 95% 54% - 98%

Hasil 1 hari – 1 bulan Langsung
Sarana Spekulum,Lampu Sorot Spekulum, Lampu sorot
Kaca Benda, Lab

Biaya Rp 15.000 –Rp 75.000 Rp. 3000

Dokumentasi Ada ( dapat dinilai ulang) Tidak ada/ ada
 2. Cervical Cytology

• Pap smear
• Liquid Based Cytology (LBC)
 Pap Smear

• The mainstay of cervical cancer

screening for the last 60 years
has been the Papanicolaou test.

• Developed in the 1940 by

Georgios Papanikolaou.

• It involves exfoliating cells from

the transformation zone of the
cervix to enable examination of
these cells microscopically for
detection of cancerous or
precancerous lesions. 1883-1962
 Teknik Tes Pap KONVENSIONAL

• Pemeriksaan ini sangat sederhana, tidak sakit, memerlukan

waktu tidak lebih dari 10 menit, serta relatif murah

Spatula dengan ujung pendek diusap Cytobrush dimasukkan kedalam kanalis

360º pada permukaan serviks servikalis, diputar 180º searah jarum jam
 Accuracy of Pap Smear
• Sensitivity = 51% for CIN I or higher
Range of 37% to 84%
• Specificity = 98% for CIN I or higher
Range of 86% to 100%
• These results are from a meta-analyses of cross
sectional studies (AHCPR 1999).
• Several ACCP studies have also found Pap test
sensitivity in the range of 50% at best.

Agency for Health Care Policy and Research (AHCPR).

Evaluation of Cervical Cytology. Evidence Report/Technology Assessment, No.
5. Rockville, MD. (1999)
 Thin Prep

Teknik Thin Prep, Masalah dan Solusi

Diambil dari : Abulafia O : Gynecol Oncol 2003 Diambil dari : Brosur Thin Prep
 What is liquid based cytology?
Collection of cellular
material into a vial of
preservative fluid
 Liquid Based
Cytology BD
SurePath™

ThinPrep

FDA
MonoPrep
Approved
 LBC vs Pap Test

• Increase in sensitivity up to 12% better for the detection of abnormalities of

low-grade squamous intraepithelial lesions with LBC compared with the Pap
smear.

• No difference between the specificity of LBC and Pap smear.

• The English pilot study showed a statistically significant decrease in the

number of inadequate samples, from 9.1% with Pap slides to an average of
1.6% with LBC (87% reduction, p < 0.0001)

• Reduced the pressure on the workforce because of fewer inadequate and

clearer to read samples.

• Reduced levels of anxiety in women because fewer need repeat tests and
because they receive their results more quickly.

• Remnant cells may be use for additional test e.g HPV DNA testing.
 Classification of Cervical Cytology

Class I Class II Class III Class IV Class V

Mild Mod Sev

Normal Inflam Cancer
Dysplasia CIS
CIN I CIN II
Normal Atypia CIN III Cancer
Koilocytosis

Benign
AS
WNL Cellular LGSIL HGSIL HGSIL Carcinoma
CUS
Changes

AS
NEGATIF LGSIL HGSIL HGSIL Carcinoma
CUS
 Lesi Pra-Kanker Serviks
(Bacaan Sistem Bethesda)
• Low grade squamous intraepithelial lesion (LSIL) :
- CIN I
- HPV Infection
• High grade squamous intraepithelial lesion (HSIL)
- CIN II
- CIN III
- Ca In situ
 3. HPV Test

• Hybrid Capture
• HPV Genotyping
99.7% of cervical cancers
are directly linked to
previous infection with a
High Risk HPV type

Walboomers et al 1999
• 14 oncogenic human papillomavirus (HPV)
genotypes (HPV16, 18, 31, 33, 35, 39, 45, 51,
52, 56, 58, 59, 66, and 68)*

• Because HPV infections are so common in

young women after sexual debut and
precancerous lesions so rare, the use of HPV
DNA testing should be delayed until 10–15
years after the average age of sexual debut in
any given population
Hybrid Capture
HPV GENOTYPING
 HPV genotyping?
• The standard HPV test only tells us if a
woman has an HPV infection, not which
type or types of HPV are causing the
infection.
 For instance, if a women has HPV 16 or HPV 18, her
HPV test would return only a ‘positive’ result.

Cervical Cancer. • HPV genotyping (also known as HPV

Photo courtesy of Thomas C.
Wright, Columbia University typing) has recently become available for
clinical use. An HPV genotyping test can
identify the specific HPV type, not just test
for the presence of any type.
 For instance, if a woman has HPV 16 or HPV 18, her
HPV typing test would return a result of ‘HPV 16’ or ‘HPV
18’
 Indication of HPV Genotyping

•Pap Smear Normal, HPV Test positive

1. Wait a year and repeat both tests. If the high
risk HPV test is still positive  colposcopy.

2. Perform HPV genotyping for HPV 16 or 18

now.

If the HPV genotyping test is positive for HPV

16 or 18  Colposcopy.

If the HPV genotyping test is negative for HPV

16 and 18,  wait 12 months and then repeat a
Pap test and HPV test (NOT genotyping).
 Triple A Guideline: ACS, ASCCP,
American Society for Clinical Pathology
CA Cancer J CLIN March 2012
Age Screening
< 21 No Screening
21-29 Cytology alone every 3 years
30-65 Preferred: Cytology + HPV every
5 years* OR
Acceptable: Cytology alone every
3 years*
> 65 No screening, following adequate
neg prior screens

After total hysterectomy No screening, if no history of

CIN2+ in the past 20 years of
cervical cancer ever
*If cytology result is negative or ASCUS + HPV negative
4. COLPOSCOPY
 Kolposkopi

Dilakukan bila hasil pap smear / IVAabnormal

 Colposcopy
• Allows direct visualization of cervix for purposes of
targeted biopsies of abnormal areas

Acetowhite Borders Mosaicism Vessels

Normal Pale Feathered None Fine/ None

Fine
Low-grade Shiny gray Distinct, Jagged Fine
punctations
Peeling or rolled Coarse
Dull oyster
High- grade edges Internal Coarse punctations
white
borders Large vessels

K Robison and DS Dizon; Dx/Rx Cervical Cancer, 2011 (Jones & Bartlett)
KOLPOSKOPI

SITOLOGI

KOLPOSKOPI

HISTOLOGI
 SENSITIVITY SPECIFICITY
HPV-DNA TEST 94.6 % 63.2 %
PAP TEST/ CYTOLOGY 55.4% 96.8 %
HPV-DNA TEST + PAP TEST 100 % 92.5%

NPV OF HPV-DNA TEST WAS 97-100%

Mayrand MH, Duarte-Franco E, Rodrigues I, etal. NEJM.2007;357:1579-88.

TERTIERY PREVENTION
TO DECREASE HIGH STAGE
CERVICAL CANCER

DOWN STAGING
 Early cervical cancer means cancer :

•Stage 1A or 1B,
•Stage 2A

Management of Early Cervical Cancer

Staging of Cervical Cancer - FIGO 2008

IIA Early Stage

Early Clinical stages of cervical cancer
I Tumor confined to cervix (diagnosed only by microscopy)

I A1 Deepest Invasion < 3mm,

Largest extension < 7mm
I A2 Deepest Invasion < 5mm,
Largest extension < 7mm

I B1 Tumor confined to cervix but larger than

st 1A and < 4 cm
I B2 Tumor confined to cervix but larger than
st 1A and > 4 cm

II Tumor with extension outside the cervix but not to

pelvic sidewall or lower third of the vagina

II A1 Tumor does not infiltrate parametria, size < 4 cm

II A2 ~ IIA, size > 4 cm

Advanced
IIB Tumor infiltrates parametrium
Clinical Staging of Cervical Cancer
Literature Data on Positive Nodes (%)

FIGO (%) Range

Ia1 0,4% (0,0 - 2,4)

Ia2 7,3% (3,8 - 13,8)
Ib 15,0% (4,3 - 34,2)
IIa 21,0% (17,0 - 34,0)
 5 Years Survival in Cervical Cancer according to
FIGO Staging

Stage Cases 5 year survival rate

I 33.179 97,4%

IA 9.528 99,3%

IB 15.084 99,2%

II 3.475 80,2%

III 2.651 59,6%

IV 3.284 28,6%

SEER data, 1988-2001. note figure are for the old staging system
FERTILITY SPARRING??
CA CX? MEMUNGKINKAN???
Radical Trachelectomy/ Dargent’s
Operation
Strict selection of patients in (Nijmegen
since 1998)
• Stage IB1 of IIA
• Tumor < 2 cm
• Childwish
• Under 40 yrs of age
• MRI /CT scan no signs of metastasis
 Operative Procedure:
part one
Transperitoneal laparoscopisc removal of pelvic
lymphnodes (eventually with sentinel node)

Management of Early Cervical Cancer

 Operative Procedure:
Part Two
Vaginal resection of cervix with vaginal cuff
and parametria

Management of Early Cervical Cancer

Radical Trachelectomy
to preserve fertility in the treatment of early cervical cancer
 5 Years Survival in Cervical Carcinoma
according to Mode of Treatment

Treatment Cases 5 year survival

rate
Surgery Alone 2.780 95%
Surgery + adj RT 1.629 85%
Surgery + adj RT 215 78%
Neoadj CT + 385 76%
Surgery
RT-Surgery 387 76%
RT alone 3.813 55%
CT alone 61 20%
No Treatment 347 9%
CT = Chemotherapy RT =
Radiotherapy
TERIMA KASIH