Screening of cervical cancer

A.A.A.N.Susraini
Department of Pathology, Medical Faculty Udayana
University/Sanglah Hospital
 EPIDEMIOLOGY
• Cervical cancer is the second most
common cancer in women in all over the
world.
• In developing countries, cervical cancer
is the first most common cancer in woman
also in Indonesia.
• In Indonesia it may constitute up to 25%
of all female cancers. It is estimated
493,000 new cases each year, over half of
which are fatal
•A study around 70’s by Zur Hausen:
There’s a relation between HPV with
cervical cancer.
Harald zur Hausen was awarded the
Nobel Prize in 2008
• Epidemiology, clinicopathology and
molecular studies  relation between
HPV type with anogenital cancer.
•
•Koss & Durfee introducing a term
“Koilosit”
• Detection of virus particle with
electron microscope, detection of
capsid with southern blot hybridization
 Human papillomavirus (HPV) is one of
the most common causes of sexually
transmitted disease in both men and
women worldwide and is thought to be
the most common sexually transmitted
viral disease
 Persistent HPV infections are now
recognized as the major cause of cervical
cancer
• Risk to HPV infection increased according
to frequency, time & number of sexual
partner.
• The incidence is increase in young lady
who has experienced sexual contact.
• HPV infection is most common in sexually
active young women, 18 to 30 years of
age..
• HPV genitalial Infection  asymptomatic not
detected by pap test
• Peack prevalence of HPV  20 th, ↓ due to
imunity & monogami sexual partner
• HPV infection decrease  50% dlm 8 bl, 90% 
2th
• persistent infection risk of precancer - cancer
• Immunology & type of virus have role in
HPV infection.
• Most cervical cancers arise at the
squamocolumnar junction between the
columnar epithelium of the endocervix
and the squamous epithelium of the
ectocervix.
HPV...

Infected the immature bacal cells in the

squamous epithelium  the viral access to the
bacal layer of the epithelium
Infected immature metaplasia squamous cells
in the squamocolumnar junction
Can not infected the superficial mature
squamous cells in the ectocervix, vagina and
vulva
Replication in the mature squamous 
citopathic effect koilocitotic atypia
Robbins 2007
• There are 15 high oncogenic risk HPVs that
are currently identified.
• From the point of view of cervical
pathology, HPV 16 and HPV 18 are the most
important.
- HPV 16 alone accounts for almost 60%
of cervical cancer cases
- HPV 18 accounts for another 10% of
cases
- other HPV types contribute to less
than 5% of cases
 Another factors for cervical cancer

Early age at first intercourse

 multiple sexual partners
 cigarette smoking
 Persistent infection with high oncogenic
HPV eg. HPV 16, 18, 52
High parity
Use of oral contraceptives
Immunosuppresion
 HUMAN
PAPILOMAVIRUS
Classification of HPV & its relationship with
type of anogenital lesion.
• Family of Papovaviridae.
• Have 2 double helix DNA, 8000 base pair.
• Unenveloped.
• Dimension 45-55 NM
• Capsidicohedral, consist of 72 capsomer.
• In human, approximately 40 type of HPV
infected the anogenital tract.
HPV
According to the infected site, HPV
divided into 3 groups:
1.Mucocutaneus group.
2.Epidermodysplasia verruciformis.
3.Genital lesion.
 According to anogenital oncogenic risk group,
HPV divided into 3 groups:
1. Low oncogenic risk.
2. High oncogenic risk.
3. Other high risk types.
• With this classification, we can predict type of
HPV infected through histological type.
 Genomic organization of HPV
divided into 3 regions
● Early region
● Late region
● Upstream regulatory region (URR / LCR )
EFEK CYTOPATHIC DARI HPV
Cicle cells of HPV
 SCREENING FOR CERVICAL CANCER

1. Pap Smear
2. DNA-HPV
3. VIA
 When to take the pap smear???
• Do not take pap smear during
menstruation.
• Stop intravaginal therapy for at least a
week before.
• Profuse Flour albus  clean it up first
with steril Gaas.
• Blood  tamponade.
• Post partum, post radiation, post SVH 
at least 6 weeks after.
 Interpretation / result
( bethesda classification system )
• Negative for intraepithelial lesion or
malignancy ( NILM )
– When there is no cellular evidence of
neoplasia, state this in the General
categorization above and /or in the
interpretation result section of the report—
whether or not there are organisms or other
non-neoplastic findings
Normal smear

Bethesda,2001
• Other non-neoplastic findings (optional to
report; list not inclusive) :
– Reactive cellular changes associated with
• Inflammation (includes typical repair)
• Radiation
• Intrauterine contraceptive device (IUD)
– Glandular status posthysterectomy
– Atrophy
• Other
– Endometrial cells (in a women ≥ 40 years of
age). Specify if “negative for squamous
intraepithelial lesion”
• Epithelial cell abnormalities
– Squamous cell
• Atypical squamous cells
– of undetermined significance (ASC-US)
– Cannot excluded HSIL (ASC-H)
• Low grade squamous intraepithelial lesion (LSIL)
(encompassing : HPV / mild dysplasia / CIN I)
• High grade squamous intraepithelial lesion (HSIL)
(encompassing : moderate and severe dysplasia, CIS;
CIN 2 and CIN 3)
– With features suspicious for invasion (if invasion is
suspected)
• Squamous cell carcinoma
– Glandular cell
• Atypical
– endocervical cells (NOS or specify in comments)
– endometrial cells (NOS or specify in comments)
– Glandular cells (NOS or specify in comments)
• Atypical
– endocervical cells, favor neoplastic
– glandular cells, favor neoplastic
• Endocervical adenocarcinoma in situ
• Adenocarcinoma
– Endocervical
– Endometrial
– Extrauterine
– Not otherwise specified (NOS)
HPV Infection
Low grade squamous Intra Epithelial Lesion
( LSIL )

Bethesda,2001
High grade Suamous Intraepithelial Lesion
( HSIL )

Bethesda,2001
Visual Inspection Acetic acid
( VIA )
DEFINITION

• EXAMINATION USING ACETIC ACID 3-5%

APPLIED TO THE CERVIX AND EXAMINED WITH
NAKED EYES.
HINSELMAN (1925)
Introduce VIA for the first time
The abnormal cervical epithelial + acetic acid 3-5% 
white (white epithelial)
The more obvious & white, more defined border 
higher the histological degree.
Time: 1-2 minutes.
The effect disappear in 50-60 seconds at normal cervix
but at abnormal cervix the white spot is not
disappear.
If there’s white lesion before applying the acetic acid
 leucoplakia (because of keratosis).
 Low-grade squamous
intraepithelial lesion( LSIL)
(LSIL).
VIA
 High-grade cervical
intraepithelialneoplasia
(CIN 2,3).
 SUMMARY
 In developing countries, cervical cancer
is the first most common cancer in woman
also in Indonesia
 HPV 16,18 were the most cause of
cervical cancer
 Screening for cervical cancer : Pap Smear ,
VIA , HPV-DNA