Premalignant Disease of the Cervix

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

Carcinoma of the cervix is  a common

killer of women in the reproductive age

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Carcinoma of the cervix is

the second commonest

cancer

among women worldwide,

with only breast cancer

occurring more

commonly



While the natural history

of breast cancer is poorly

understood

, cervical

cancer is a preventable

condition and considerable

effort goes into detecting

and treating the pre

invasive disease.

P

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

The cervix

is a tubular

structure

between

the uterus

and vagina

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:

The ectocervix is

covered by

squamous

epithelium .The

canal of the cervix,

however, is lined by

columnar

epithelium, and the

point where these

two epithelia meet

is called the

squamocolumnar

junction (SCj)

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

The cervical canal is lined

by columnar epithelium,

this epithelial exposed to

the acid environment of

the vagina under goes a

process of metaplasia

where by it becomes

squamous epithelial.

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The

transformation

zone 

TZ 

is an

important area

on the cervix

which is defined

as the area

where the

original SCJ was

to the current

SCJ and it

includes areas of

metaplasia.



The transformation

zone (TZ) is the site

where

premalignancy and

malignancy develop

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:



The process of the

metaplasia can be

disrupted by external

influences and lead to

disordered squamous

epithelial called

dysplastic epithelial



Squamous metaplasia

should not be diagnosed

as dysplasia (or CIN)

because it does not

progress to invasive

cancer.



HPV is now implicated in this

process.

Approximately 99-100 % of

intraepithelial neoplasia is

attributed to human papillomavirus

(HPV) infection 

is a 

common

sexually transmitted infection (STI)



 Smoking



and immune suppression appear to

be additional factors which may act

as co- agent.

(

C

I

N

)

.



These dysplasia  now termed

cervical intra epithelial

neoplasia

CIN



which has the potential

to turn malignant

without treatment

(

C

I

N

)

.



CIN I 

(mild dysplasia)

.: affected only the deepest third

of the epithelium from the basal layer upward, with

maturation seen more superficial to that



CIN II 

(moderate dysplasia)

: affected the second third

of the thickness of the epithelium.



CIN III 

(severe dysplasia, carcinoma in situation)

.

show no maturation throughout the full thickness

(

C

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N

)

.

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

In North America and many

other countries, the Bethesda

reporting system has been

adopted. The classification

uses the 

term squamous

intraepithelial lesion 

(SIL)

to encompass all grades of

CIN. SIL is further subdivided

into two categories :

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(LSIL)

  low grade  which includes

cellular changes associated with

human papilloma virus (HPV)

infection and CIN 1

. low

progressive potential

(HSIL)

 high-grade SIL which

includes CIN 2 and 3. 

are likely

to behave as cancer precursors



All CIN are reversible

lesions (i.e. curable

lesions) and directed

more to malignancy

with increase the

degree of dysplasia

.

High-grade disease is

less likely to regress

spontaneously and

requires treatment

as there is a risk of

progression to cancer

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

1.Cytology



2.Histology.



3.Colposcopy

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:



(

left slide ) 

Conventional

cervical cytology 

is prepared by

smearing collected cells directly

onto a glass slide with the

collection device followed by

immediate fixation



(

right slide ) 

Thin-layer 

liquid-

based cytology 

involves transfer

of collected cells from collection

device into a liquid transport

medium with subsequent

processing and transfer onto a

glass slide. Cells



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

The NHS screening

program now uses

liquid based

cytology (LBC)

for

screening.

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

Who

 to screen(Any woman with a cervix who

has ever had sexual intercourse)

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The American Congress of Obstetricians and Gynecologists

currently recommends that cervical cytology screening

begins at age 21 years, regardless of sexual activity or

other risk factors.



Cervical cancer is

extremely rare in women

younger than age 21 (1

case per million), and

screening adolescents has

not been successful in

preventing these rare

cancers

In addition, adolescents have higher incidence of HPV-

related dysplasia because the cervix is immature, 

but

most of these lesions

resolve without

treatment

, so screening in this population

may lead to unnecessary and potentially harmful

treatment.

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women 21-29 years should

be screened every

3years,they should not

be tested for HPV unless

it  is needed after an

abnormal Pap smear .

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?

Women 30-65 years of age should be screened with both

cytology (using the conventional Pap or liquid-based

method) combined with HPV testing every 5 years

(preferred) 

or with cytology alone every 3years

(acceptable). 

screening can stop at age 70 if there has

been no abnormal Pap test result in the past 10 years

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

Age 65 and “adequate recent

screening”



Three consecutive normal pap

smears



No abnormal pap smears in last

10 years



No history of DES exposure



No history of cervical or uterine

cancer

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

Hysterectomy for benign

disease



USPSTF recommends

discontinuation



Hysterectomy for invasive

cervical cancer



ACOG and ACS recommend

continued screening

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

A colposcope is a

microscope with

magnification of 

5-20

times

, by which would be

able to recognize the

earliest lesions of the

cervix that were invisible

to the naked eye.

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A test 

used

 to identify normal squamous epithelium which

contains glycogen that stains dark brown with iodine,

after application of lugol iodine solution.

While abnormal squamous cells (lack of glycogen) fail to

stain and appear bright in colour which is the site for

biopsy (colposcopic –directed biopsy).



The use of

 3-5% acetic

acid

 to visualize the

abnormal epithelium show

the CIN as white area

compared with pink normal

squamous epithelium

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Acetowhite epithelium.

Punctation (dilated

elongated vessels).

Mosaic (crazy paving

appearance).

Abnormal blood vessels

(coma –shape, wires) in

invasive cancer.

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:

1.Ideally all women with abnormal cervical cytology should

have colposcopic assessment except patient with (CIN1)

PAP smear could be repeated after 6 months ,if still

positive referred for colposcopy

three normal smears are requiring before a women can be

returned to routine screening in case of mild dysplasia.

2.

Women with CIN ll &CIN lll

are referred for colposcopy.

3.

Smears show abnormal

glandular cell should always

referred to colposcopy

because of increase risk of

invasive cancer.



Result of colposcopic directed

biopsy or cone biopsy if revealed :



invasive cervical cancer treatment

by(radical surgery

 , 

radiotherapy,

chemotherapy ) ,but  if the result

revealed CIN  the treatment will

be as bellow:



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

However, CIN 2

and CIN 3 are

treated by

excision or

ablation  .

Ablative techniques

1- 

CRYOCAUTERY:

 Destroys tissue by freezing to a depth of

approximately 

4 mm

. 

is sufficient treatment for low-

grade CIN, but not effective enough for high-grade

disease.

.

2- 

ELECTRODIATHERMY:

 More effective than cryocautery,

it requires general, regional or local anaesthesia. It

destroys up to 

1 cm

 depth.

.

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59

3- 

COLD COAGULATION: 

. is a misnomer as the treatment

involves placing a hot probe on the cervix in outpatients

under local anaesthetic. It is a destructive treatment, is

effective forboth high- and low-grade CIN but does not

provide a specimen.

4-  

LASER:

, it allows good control of the depth of

destruction, good haemostasis and excellent healing as

there is minimal thermal damage to the adjacent tissue

attached to Colposcope , Depth of destruction 

5-7 mm

EXCISIONAL METHODS

TZ excision has been developed as a conservative excisional

technique.

1- 

LASER TZ EXCISION.

2- 

DIATHERMY LOOP EXCISION.

Large loop excision of TZ 

(

LLETZ

) in Europe and 

loop

electrosurgical excision procedure 

(

LEEP

) in North

America, both can be used to fashion cone biopsies of

the cervix.

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61

L

L

E

T

Z

O

t

h

e

r

m

o

d

a

l

i

t

i

e

s

i

n

c

l

u

d

e

s

:

Knife cone biopsy

Laser cone biopsy

Loop cone biopsy

hysterectomy

C

o

n

i

z

a

t

i

o

n



Conization of the cervix plays an important role in the

management of CIN. Before the availability of

colposcopy, conization was the standard method of

evaluating an abnormal Pap test result.

C

o

n

i

z

a

t

i

o

n



Conization is both a

diagnostic and therapeutic

procedure and has the

advantage over ablative

therapies 

of providing tissue

for further evaluation to

rule out invasive cancer

C

o

n

i

z

a

t

i

o

n

i

s

i

n

d

i

c

a

t

e

d

f

o

r

d

i

a

g

n

o

s

i

s

i

n

w

o

m

e

n

w

i

t

h

H

S

I

L

b

a

s

e

d

o

n

a

P

a

p

t

e

s

t

u

n

d

e

r

t

h

e

f

o

l

l

o

w

i

n

g

c

o

n

d

i

t

i

o

n

s

:

●Limits of the lesion cannot be visualized with colposcopy.

●The SCJ is not seen at colposcopy.

●Endocervical curettage (ECC) histologic findings are

positive for CIN 2 or CIN 3.

●There is a substantial lack of correlation between

cytology, biopsy, and colposcopy results.

C

o

n

i

z

a

t

i

o

n

●Microinvasion is suspected based on biopsy, colposcopy, or

cytology results.

●The colposcopist is unable to rule out invasive cancer.

.

When colposcopy is not available

C

o

m

p

l

i

c

a

t

i

o

n

:



1.Immediate 

(infection and haemorrhage).



2

.

L

a

t

e

(

c

e

r

v

i

c

a

l

s

t

e

n

o

s

i

s

,

c

e

r

v

i

c

a

l

i

n

c

o

m

p

e

t

e

n

c

e

a

n

d

i

n

f

e

r

t

i

l

i

t

y

)

C

o

n

i

z

a

t

i

o

n

C

o

n

i

z

a

t

i

o

n

H

y

s

t

e

r

e

c

t

o

m

y



There are some situations in

which hysterectomy remains a valid and appropriate

(although mandatory) method of treatment for CIN:

1.

Microinvasion CIN 3 at limits of conization specimen in

selected patients

2.

Poor compliance with follow-up

3.

Other gynecologic problems requiring hysterectomy,

such as fibroids, prolapse, endometriosis,and pelvic

inflammatory disease