CERVICAL CANCER

Sutrisno
Obstetric and Gynecology Department
Medical Faculty
Jenderal Soedirman University
Prof. Dr. Margono Soekarjo Hospital
2018
 CERVICAL CANCER
• Anatomy
• Pathogenesis
• Etiology
• Risk Factor
• Symptom
• Stage
• Therapy
 The cervix and vagina are derived from the müllerian ducts and are initially lined by a single
layer of müllerian-derived columnar epithelium. At 18 to 20 weeks of gestation, the columnar
epithelium lining the vaginal tube is colonized by the upward growth of stratified squamous
epithelium derived from cloacal endoderm.
CERVICAL CANCER in INDONESIA
• The most cancer in Indonesia
• > 60 – 70 % advanced stage

• No program for mass screening

 Cervical cancer is the third most common cancer
among women worldwide and is
entirely attributable to infection with the Human
Papillomavirus (HPV).

The higher incidence and death rates of

cervical cancer in low
resource settings are likely to result
from the lack of organized
cervical screening and inadequate access to
treatment.
The primary goal of cervical screening is to prevent cervical
cancer.
Location of squamocolumnar junction at various times in a woman’s life. CE, columnar
epithelium; SE, squamous epithelium; SCJ, squamocolumnar junction.
New SCJ
1. Eversion/ectropion
2. Exposed to the acidity of vagina
3. Stromal proliferation underlying columnar epithelium
4. Immature, undifferentiated, stratified, squamous, metaplastic epithelium
The Anatomy Of The Transformation Zone
 The Four Major Steps In The Development Of
Cervical Cancer

• Infection of the metaplastic epithelium of the

transformation zone with one or more carcinogenic HPV
types
• Viral persistence rather than clearance
• Progression of persistently infected epithelium to
cervical precancer (CIN 3) (potentially reflecting the host
immune response and/or exposure to the confirmed
cofactors for HPV progression, which include
multiparity, age at first full-term pregnancy, use of oral
contraceptives, and current tobacco exposure)
• Invasion
 Colpophotograph of cervix of 25-year-old women with low-grade
ectocervical SIL, an internal margin
with a high-grade central lesion revealing an atypical vessel at a
focus of microinvasive cancer.
Colpophotograph of cervix of a 33-year-old woman with a high-
grade SIL showing a “ridge” sign or
raised, rolled, peeling margin at an area of early invasion.
The HPV genome and its expression within the epithelium. The HPV genome consists of approximately 8,000 base
pairs of single-stranded, circular DNA. HPV genes are designated as E or L according to their expression in early
or late differentiation stage of the epithelium: E1, E2, E5, E6, and E7 are expressed early in the
differentiation, E4 is expressed throughout, and L1 and L2 are expressed during the final stages of
differentiation. The viral genome is maintained at the basal layer of the epithelium, where HPV
infection is established. Early proteins are expressed at low levels for genome maintenance (raising the possibility
of a latent state) and cell proliferation. As the basal epithelial cells differentiate, the viral life cycle enters
successive stages of genome amplification, virus assembly and virus release, with a concomitant shift in
expression patterns from early genes to late genes, including L1 and L2, which assemble into viral capsid.
(Reproduced with permission from Schiffman M, Castle PE, Jeronimo J, et al. Human papillomavirus and cervical
cancer. Lancet. 2007;370;890–907.)
Major steps in the development of cervical cancer. Incident HPV infection is
best measured by molecular tests. Most HPV infections show no concurrent
cytologic abnormality. Approximately 30% of infections produce
concurrent cytopathology, usually nonclassical (equivocal)
changes. Most HPV infections clear within 2 years. Ten
percent persist for 2 years and are highly linked to
development of precancer. Top image reproduced with permission from
Schiffman M, Castle PE, Jeronimo J, et al. Human papillomavirus and cervical cancer. Lancet.
2007;370:890–907; Bottom image reproduced with permission from Mark Schiffman M,
Wentzensen N. Human papillomavirus infection and the multistage carcinogenesis of cervical
cancer. Cancer Epidemiol Biomarkers Prev. 2013;22(4);553–560.
 CERVICAL CANCER

NATURAL HISTORY

PRA - CANCER CANCER

15 % 30 % 45 %

MILD MODERATE SEVERE STAGE 0

NORMAL INVASIVE
DYSPLASIA DYSPLASIA DYSPLASIA

40 % 20 %

Low grade SIL High grade SIL

IDENTIFIED by METHODE VIA
ETIOLOGY
TYPE OF LESION,NATURAL HISTORY AND
HPV TYPING

Type of HPV Lesion Natural history

6 Condiloma acuminata Benign

Flat Condiloma Benign
6, 11 Verrucous cancer Local Destruction
Condiloma acuminata Benign
Flat Condiloma Benign
16, 18 Lesion,white, flat Neoplastic
31, 33 Papulosis bowennoid Canker and cancer
39, 42 perkusor

already known HPV type 70

RISK FACTOR
OF CERVICAL CANCER
• Intercourse (married) at an early age (< 20 year )
• Multiple sexual partners
• Exposed of STD (Sexual Transmitted Disease )
• Women of SMOKE
• Deficiencies of Vit A./Vit C/Vit E
 RISK of CERVICAL CANCER
AGE
The most AGE 35 – 49 year
35.00

30.00

25.00

20.00

15.00

10.00

5.00

-
<15 15-24 25-34 35-44 45-54 55-64 65-74 >75
 Risk of CERVICAL CANCER
Sexual Partner

Sexual Partner
= >5 : 12 x
Risk of Cervical Cancer
SMOKING

Risk 2,7 x
 Risk of Cervical Cancer
Multiple Pregnant and Deliveries

• Trauma
• Nutrition
• Hormon at pregnant
 PREVENTION of
CERVICAL CANCER
 Primair, avoid of etiology and risk factor

 Secunder, screening for high risk women

 Tertier, or chemoprevention,
natural componen or
Sintetic extract
(beta caroten, Vit C, E)
Risk of Cervical Cancer
Nutrition

 Beta caroten, protectif efect 3 x

 Vit C, traumatic recovery of
the cervix, antioksidant corelated
with immunity and smoke
protection
 Vit E, protection of precancer
lesion
 Folic Acid ?
Risk of protective
of Cervical cancer
Pap’s smear

The last result of

Pap’s Smear was NORMAL
Risk protective of Cervical Cancer
Contraception

 Intra uterine Device

IUD/spiral
 Condom

Protection of
Cervix from Cervix from
Virus infecsction
 Risk protectif of Cervical Cancer
Genitalia hygine

Hygine of genitalia protect

from infection
 SIGN and SYMPTOM
• Vaginal bleeding
• Fluor albus
mixed with blood ,odour
• Pelvic pain
• Anuri

Women with vaginal bleeding and

fluor albus not automatically causes
of Cervical Cancer
SYMPTOMS

Vaginal bleeding
……….. CANCER ?
EARLY DETECTION METHODE
CERVICAL CANCER

• PAP’ S SMEAR
• VISUAL INSPECTION = VIA
• GYNESCOPI

• SERVICOGRAPHY
• COLPOSCOPY
• PAPNET (by COMPUTER)
• THIN PREP
• HPV TESTING
....
PAP’S SMEAR

1. Smear by Eyre spatula on

ectocervix, 2).
Twist on object glass

2. Smear by “Cytobrush” on
endocervix,
Twist on object glass 1).

3. Dip the object glass in

alcohol 96%, minimal 30’
CERVICAL CANCER SCREENING

PAP’S SMEAR
Sensitivity ( 70 – 80% )
Specificity ( 90 – 95 % )
Relative “low cost”
Easy
Good acceptanse
CERVICAL CANCER SCREENING

PAP’S SMEAR
Man power, Facility, Network,
Organisation

Developing country (?)

Other aternatif (?)

PAP’ SMEAR
in INDONESIA ?
Man Power :
Obs – Gin 1135
Pathologist < 300
Screener < 150
MIDWIFES ± 70.000

Can it conducted at all Indonesia ?

EARLY DETECTION METHODE
CERVICAL CANCER

• PAP’ S SMEAR
• VISUAL INSPECTION = VIA
• GYNESCOPY

• SERVICOGRAPHY
• COLPOSCOPY
• PAPNET (by COMPUTER)
• THIN PREP
• HPV TESTING
....
CERVICAL CANCER SCREENING
by V I A
VIA
White Epithelium by acetic acid
Simple methode-can be done at all Primary health centre

• Light resouce
• Vaginal Speculum
• Gynecologic bed
• Acetic Acid 3-5%
• Cotton bud
• Gloves
 VIA
Visual Inspection with Acetic Acid
Non-invasive
Easy to do – Low Cost
At Primary Health Care Center
Direct Result
Sensivity dan spesificity

Suitable for DEVELOPING COUNTRY

VIA
Provider
• Midwifes
• Nurse with Competency certification
• Medical Doktor
• Obs Gynecologist
Tampilan pemeriksaan IVA

Sebelum asam asetat

Bercak putih

Setelah asam asetat

Criteria of VIA result
I. Normal
II. Inflamation - cervicitis
III. VIA positive : White Epithelium
IV. Cervical Cancer
TAMPILAN I V A
I

NORMAL

II

OVULA NABOTI

EKTOPI SERVIKS
TAMPILAN I V A

III.
LESI PRA KANKER

Lesi intra epitel serviks

derajat rendah
~ NIS I
TAMPILAN I V A

IV.
KANKER SERVIKS
Invasif
 V.
Servikografi
Kamera yang menghasilkan panoramik
gambar serviks dengan resolusi tinggi.

Tes pelengkap yang meningkatkan

sensitivitas dan spesifisitas tes pap untuk
mendeteksi lesi prakanker dan kanker
serviks.
EARLY DETECTION METHODE
CERVICAL CANCER

• PAP’ S SMEAR
• VISUAL INSPECTION = VIA
• GYNESCOPI

• SERVICOGRAPHY
• COLPOSCOPY
• PAPNET (by COMPUTER)
• THIN PREP
• HPV TESTING
....
 VI.

Diagnostic test
Colposcopy
EARLY DETECTION METHODE
CERVICAL CANCER

• PAP’ S SMEAR
• VISUAL INSPECTION = VIA
• GYNESCOPI

• SERVICOGRAPHY
• COLPOSCOPY
• PAPNET (by COMPUTER)
• THIN PREP
• HPV TESTING
....
 Reading the PAP’S SMEAR
result

Pap net
• Mengatasi screening errors

Thinprep
• Mengatasi kegagalan mengambil
spesimen, fiksasi tidak adekuat, distribusi
acak sel abnormal, element kabur,
berbagai tehnik smir
EARLY DETECTION METHODE
CERVICAL CANCER

• PAP’ S SMEAR
• VISUAL INSPECTION = VIA
• GYNESCOPI

• SERVICOGRAPHY
• COLPOSCOPY
• PAPNET (by COMPUTER)
• THIN PREP
• HPV TESTING
....
EARLY DETECTION METHODE
CERVICAL CANCER

• PAP’ S SMEAR
• VISUAL INSPECTION = VIA
• GYNESCOPI

• SERVICOGRAPHY
• COLPOSCOPY
• PAPNET (by COMPUTER)
• THIN PREP
• HPV TESTING
....
 Kanker Mulut rahim

HPV TESTING
HPV difficult to culture
For early detection and HPV
typing
3 TEST
Hybrid Capture 2 ( HC2)
Polymerase Chain Reaction (PCR)
In Situ Hybridization (ISH)
 Kanker Mulut rahim

TIPE HPV ~ Risiko

• Low risk
- 6, 11, 42, 43, 44
• High risk
– 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68
Stadium Kanker Serviks
EARLY DETECTION METHODE
CERVICAL CANCER

• PAP’ S SMEAR
• VISUAL INSPECTION = VIA
• GYNESCOPI

• SERVICOGRAPHY
• COLPOSCOPY
• PAPNET (by COMPUTER)
• THIN PREP
• HPV TESTING
....
VIA ……..

Look at through the vagina ,

It will salvage a women from
Advanced cervical cancer ………………..