CARCINOMA

CERVIX
BY :
SITI MUNIRAH KAMARUDIN
NOR ELYA FARHANA BINTI ABDUL RAZAK
OUTLINE
INTRODUCTION
EPIDEMIOLOGY
ETIOLOGY
DIAGNOSIS
CLASSIFICATION
MANAGEMENT
PREVENTION
INTRODUCTION
Cx ca is the most common gynecologic ca in women

Most of ca cx stem from infection with Human Papilloma
Virus (HPV)

Dx : colposcopic examination and histologic evaluation
of cervical biopsy

This ca is staged clinically the most important indicator
of long term survival

Prevention lies mainly in early detection regular Pap
smear screening



EPIDEMIOLOGY
1 million fresh cases/year across the globe

2nd commonest cancer in women (parkin 2005)

Incidence is decreasing in developed countries

Pap smear has reduced incidence by 80%&
death by 70%

Most common CA in developing countries



Risk factors
Early intercourse(<16yrs)

High parity

Early age of pregnancy

Too many/ too frequent pregnancy

Multiple sexual partners

OCPills

Smoking

Lower socioleconomic
Pathogenesis
Cx epithelium-> infection->hpv dna
integration to human genome-> up
regulation of viral oncogenes-> expression
of E6&E7 oncoproteins ->interference with
tumor suppressor genes-> host cell
immortalization, HPV induced euplastic
transformation
HISTOPATHOLOGY
Squamous cell carcinoma is the
commonest (80-90%)
Well differentiated, moderately
differentiated, poorly differentiated
Source- healing erosion, squamous
metaplasia of columnar epithelium,
squamous cell rests in ectocx
HISTOPATHOLOGY
Adenocarcinoma (10-15%) develops
from endocervical canal- from lining
epithelium/glands
Occurs at young age
80% purely endocervical type
Others- endometroid, clear,
adenosquamous, or mixed
DIAGNOSIS
SYMPTOMS
Early stage : watery , blood tinged p/v
d/c
irregular/continuos bleeding
Offensive discharge
Lower extremity edema
Low back pain
Bladder, Rectal symptoms , Ureteral
obstruction



P/S
Lesion may appear as
Exophytic or endophytic growth
Polypoid mass
Papillary tissue
Barrel shaped cx
Ulceration







invasive cervical cancer originating from the
endocervix
Bimanual examination
may palpate
indurated, friable, bleeding to touch
thick, hard , irregular rectovaginal septum

Rectal examination
Parametria involvement
Feel thick, irregular, firm , less mobile




FIGO Staging
A clinical classification
According to:
vaginal examination
rectal examination
cystoscopy
* FIGO International Federation of Gynaecology and Obstetrics
Stage 0 - CIN III(CIS)
Stage I confined to the cervix
Ia - Microscopic
1a1 Stromal invasion 3mm,
Width 7 mm
1a2 stromal invasion 3 5 mm,
Width 7 mm
Ib Macroscopic
1b1 Lesion 4 cm
1b2 Lesion > 4 cm
Stage II extend beyond the cervix but not to
the pelvic wall and lower third of the vagina
IIa
Extend to the upper two third
of the vagina
IIb
Extend to the parametrium
Stage III Extend to lower one third of vagina
or pelvic wall
IIIa
Involvement of the lower one
third of the vagina
IIIb
Involvement of the pelvic wall/
hydronephrosis or non-
functioning kidney
Stage IV extend beyond true pelvis, involve
bladder or rectum
IVa
Spread to adjacent organ
(bladder, rectum)
IVb
Spread to distant organ
MANAGEMENT
Stage O ablative
techniques (cryosurgery,
cone biopsy)

Stage Ia cone biopsy or
hysterectomy

Stage Ib and IIa
Wertheims hysterectomy

Stage I, II, III
combination intracavity
radioisotope and high-
energy external radiation
therapy, for eg : caesium-
137

Stage IV external
radiotherapy if the
disease confined to the
pelvis. If spread ouside -
chemotherapy
Indicated in :
Advance disease with
extrapelvic spread
Recurrent disease
Where radiotherapy has been
ineffective

Most tx are based on
cytotoxics based on
cisplatin

Not 1
st
choice of tx :
Relatively radiosensitive
Large, bulky tumours may have
necrotic centres which ar enever
reach
Tissue vascularity is reduced
following radiotherapy, so drug
uptake is sub-optimal
SURGICAL RADIOTHERAPY CHEMOTHERAPY
Pre-invasive (Ca in situ, CIN III)
Ablative Technique
Destroy abnormal cervical
tissue
Cryosurgery
Diathermy
CO2 laser
Excisional Technique
Tissue is obtained and
examined histologically
Large loop
electrodiathermy of the
transformation zone
(LLETZ)
Knife cone biopsy
Laser cone biopsy
*** All women who have had CIN before should be followed up with
annual smears for a minimum of 10 years.
Wertheims hysterectomy
Radical
hysterectomy
Bilateral lymph
node clearance
+
Favoured in :

Pre-menopausal women
Where the tumour is
small
When the future child
bearing is not wished
Complications :

uriteric fistula or stricture
bladder dysfunction
DVT and PE
Palliative
-Pain control
-radioRx - bleeding
Prognosis
Stage I - > 85%
Stage II 50%
Stage III 25%
Stage IV 5%

In patients with recurrent disease :
50 % show recurrence within 1 year
75% show recurrence within 2 years
90% show recurrence in 5 years
STAGE SPREAD TREATMENT

PROGNOSIS
(5-year survival %)
I a

I b

II a

II b

III

IV
Cervix (micro-invasive)

Cervix (macro-invasive)

2/3
rd
upper vagina

Parametrium

1/3
rd
lower vagina, pelvic walls

Bladder, rectum or metastases
Local excision

Radical surgery

Radical surgery

Radiotherapy

Radiotherapy

Palliation
100

80

60

50

30

10
PREVENTION STRATEGIES
CERVICAL CYTOLOGY
SCREENING
PROGRAMME
PROPHYLACTIC HPV
VACCINE
Methods of Screening
Pap smear
Colposcopy

How to take?
Explain to the patient/consent
Not during menstruation
The best time is on D10 - D20
Avoid douching, using spermicidal gel.
Avoid sex 24 hours prior to the procedure

Patient in dorsal/lithotomy position
using the Cuscos bivalve speculum to visualize
the cervix
Place the wooden spatula (Ayres spatula) on
the cervix and rotate 360 clockwise and make
sure cover all the transformation zone
Immediately smear it on the glass slide
Fix the slide with fixative agent either spray or
ethanol 95%

Speculum
Insert Speculum
Spread labia
Keep labia apart
Blades remain closed
until fully inserted

Squamo-Columnar Junction
Junction of pink cervical
skin and red endocervical
canal
Inherently unstable
Key portion of the cervix
to sample
Most likely site of
dysplasia
Ayres Spatula
Sample Cervix
Use concave end
Rotate 360 degrees
Dont use too much force
(bleeding, pain)
Dont use too little force
(inadequate sample)

How to interpret?
Dyskaryosis - abnormal nucleus of individual
the cell.
Dysplasia - abnormality in organised growth of
the cell.
CIN refers to a lesion in epithelium of the
cervix
New technique Bethesda system
Cervical Intraepithelial Neoplasia
CIN I Mild dysplasia
CIN II Moderate displasia


Severe dysplasia
CIN III
Carcinoma in situ
CIN I
Alterations are limited to the lower third of the cervical epithelium
CIN II
The cell polarity is disturbed in the lower two thirds of the epithelium
CIN III
Dyspolarity is present in more than two-third or all layers of the epithelium.
Natural history of CIN 1-2
**(100 prospective studies)

STAGE/PROGRESS Regress Persist CIN III Cancer

CIN I


57%

32%

11%

1%

CIN II


43%

35%

22%

5%
Bethesda System
Specimen adequacy
Satisfactory for evaluation
Unsatisfactory for evaluation (specify reason)
Specimen rejected/not processed (specify
reason)
Specimen processed and examined but
unsatisfactory for evaluation (specify reason)

When to start?
Within 3 years of 1st coitus or by age 21
How frequent
Every two years provided the last smear is
normal
When to stop?
No limit

Colposcopy
Technique of viewing cervix using binocular
microscope with low magnification to
determine the source of abnormal cells
Indication: abnormal finding on Pap smear
Procedure
Position patient in lithotomy position

1. LOOK
Using the speculum to visualize the cervix

2. ACETIC ACID
Apply 3-5% acetic acid for at least 60sec prior to
inspecting for changes
Acetic acid dissolves mucous and accentuates
atypical areas (white epithelium, punctation,
mosaic and atypical vessels) by causing cellular
dehydration and coagulation of cellular protein.
The effect of the acetic acid peaks in ~ 2 min and
fades in ~ 5 min. Re-apply the acetic acid solution
several times.
Biopsy the acetowhite epithelium





A. Benign surface vessels viewed through a colposcope using usual white light
source.
B. Use of a blue-green (red-free) light filter provides higher contrast and
definition of vascular patterns.




A. Cervix after application of acetic acid. Several areas of acetowhite change adjacent to the
squamocolumnar junction are apparent.
B. Same cervix after application of Lugol iodine solution. Non-staining of the lesions at the 10 to
11 o'clock positions is seen (black arrow) while there is partial iodine uptake of acetowhite areas
along the posterior SCJ (white arrow).

3. BLOOD VESSEL PATTERN
Using the green filter to improve the ability
to identify the vascular patterns (mosaic,
punctation, atypical)

VACCINES
Star 21
st
July 2009
Cumulative Incidence of Any HPV Infection

What is HPV ?
HPV is short for human
papillomavirus

HPVs are a groups of over
100 related viruses

Each HPV virus in the group
is given a number, which is
called an HPV type.




American Cancer Society, Inc 2008

Human Papillomavirus Types and
Disease Association
nonmucosal/cutaneous
(~60 types)
skin warts
(hands and
feet)

mucosal/genital
(~40 types)
high-risk types
16, 18, 31, 45
low-risk types
6, 11
low grade cervical
abnormalities
cancer precursors
genital cancers

low grade cervical
abnormalities
genital warts
laryngeal papillomas
How is HPV related to cervical cancer?
53.5
2.3
2.2
1.4
1.3
1.2
1.0
0.7
0.6
0.5
0.3
1.2
4.4
2.6
17.2
6.7
2.9
0 10 20 30 40 50 60 70 80 90 100
X
Other
82
73
68
39
51
56
59
35
58
52
33
31
45
18
16
Almost all (more than 99 %) cervical cancers are related to HPV.
Of these, about 70% are caused by HPV types 16 or 18.
American Cancer Society, Inc 2008
Muoz N et al. Int J Cancer 2004; 111: 27885.
Vaccine Available
When, Why, How
WHEN can you prescribe CervarixTM?
Prescribe now for girls and women, as they remain at risk
of infection from oncogenic HPV throughout their lives.
WHY prescribe CervarixTM?
CervarixTM, with its novel adjuvant AS04, provides strong and
sustained protection against cervical cancer.1,3,4,25-32
Induces antibody levels that start high and stay high for both HPV 16/18.
HOW do you administer CervarixTM?
Give 3 doses of CervarixTM at 0, 1, 6 months.
Vaccination is by intramuscular injection into the deltoid area.
star 21
st
July 2009
THANK YOU
Referrence
Gynaecology companion, Dr Mohd Azhar Mohd Noor
Clinical Practice Guidelines (CPG), Management of Cervical Ca 2003
Gynaecology by Ten Teachers, 18
th
edition
Quick Management Guide in Gynaecology, Lee Say Fatt, UM 2008