this lecture for undergraduates, GP & gynecologists it includes full simple explanation of CIN (cervical intraepithelial neoplasia) how to do screening for cervical cancer methods of screening that include pap smear and HPV testing it also includes the diagnostic method for the cervical cancer by taking biopsy directed by colposcopy colposcopy and its rule how to deal with CIN different grades follow up after CIN treatment

1. CIN and cervical
cancer screening
By
Dr. Ahmed Mohamed Nasef
Assistant lecturer in Obstetrics &
Gynecology department
Benha University

2. Objectives
• Discuss CIN
• Cervical cancer screening
• Pap smear
• Pap smear
• Colposcopy

3. CIN (cervical intra epithelial neoplasia)
Malignant change in the cell lining the cervix without invasion of the basement membrane
Dyskaryosis abnormal change in nuclei and cytoplasm
Age of Incidence 20-40 years old
Most common site for CIN is the TZ (transformation zone)

4. TZ (transformation zone)
• It the area of the cervix between the new & original
squamocolumnar junction
• It is area formed of partially squamous, partially
columnar and partially metaplastic epithelium
• So it is an area of unstable epithelium between the two
junctions

5. TZ
• In prepubertal age
• the squamocolumnar junction is present just
within the cervical canal
• Upon entering puberty
• Due to hormonal influence & during pregnancy
the columnar epithelium extends over ectocervix
this causes squamocolumnar junction to move
outwards onto vaginal portion of cervix
• The exposed columnar epithelium to vaginal
acidity will undergo physiological squamous
metaplasia

6. Risk factors
STDs (HPV, HIV, HSV)
Early age at 1st intercourse
Multiple sexual partners
Uncircumcised male partner
History of STDs
OCPs
Smoking

7. HPV
dsDNA virus
Member of papova family
Transmission
Direct sexual contact
Homosexuals
Autoinoculation in orogenital sex
There are more than 120 HPV types
HPV types 16& 18 are the most oncogenic ones

8. Mechanism
of
oncogenesis
by HPV
Viral DNA integrate itself into host cell genome
Expression of viral E6&E7 genes
Production of oncoprotiens leads to inactivation of
p53 tumor suppressor gene
Leading to tumor cascade start

9. Pathology
Macroscopic
Site at the TZ
No lesion
Predisposing factor
Microscopic
According to extent of malignant
cells in the thickness of epithelium
divided into:
CIN 1 affect only lower 1/3 of
epithelium
CIN 2 affect only lower 2/3 of
epithelium
CIN 3 affect more than lower 2/3 of
epithelium
In all there is no invasion of the
basement membrane

10. CIN grades

11. Clinical presentation
Symptoms
Asymptomatic
Predisposing factor
Contact bleeding
Signs
No signs
Suspicious cervix
Most cases diagnosed during
routine screening

12. Here comes a question ????
There is no symptoms nor signs in
most cases
So what to do??????!!!!!!!!

13. So come the role of
screening tests
Aim
To detect and find cases of CIN early
before transformation to cervical
cancer
So it’s a way to prevent cervical
cancer

14. To whom we will do
screening?
All female population

15. When?
Age 21-65 years
Not recommended for:
< 65 years old with three
consecutive negative pap tests or 2
consecutive negative HPV tests + no
history of CIN in past 20 years
Women who have had total
hysterectomy + don’t have history of
CIN

16. Types of screening tests
Pap smear
• Done every 3 years
• No HPV with it
HPV testing with pap smear
• Done every 5 years

17. HPV testing
• Obtain sample by cervical smear
• Tested by PCR & DNA probing

18. HPV testing screening

19. Pap smear
• First to be done by George
papinacolaou 1950, hence
the name pap testing

20. Pap smear
Aim :
To obtain cells from cervix (TZ) for cytological examination

21. Pap smear
steps
• Outpatient procedure
• Placing speculum in the vagina
• Scraping cervical cells by Ayres
spatula and endocervical brush
• Cells sampled from the TZ
• Samples fixed on a slide by alcohol
or put in a liquid
• Then sent to lab for cytological
examination

22. Ayres spatula & brush

23. Reporting of the pap testing
Reported by the Bethesda system into:
Normal
Negative for any change
Atypical squamous cells of undetermined significance (ASC-US) or (ASC-H)
Most common squamous abnormality
Mean that few cells show intraepithelial lesion
Low grade squamous intraepithelial lesion (LGIL)
Mostly related to CIN 1
High grade squamous intraepithelial lesion (HGIL)
Mostly related to CIN 2&3
Atypical glandular cells (AGC)
Risk of invasive cancer with it is high (about 3% to 17%)
May originate from endometrium or endocervix

24. What to do after cytology report?
Pap smear
Negative
Return to routine
screening
program
Positive
ASC
ASC-US
HPV
Negative
Return to routine
screening
program
Positive
Colposcopy
ASC-H
Colposcopy
LSIL
HPV
Negative
Repeat pap &
HPV after 12
months
Positive
Colposcopy
HSIL
Colposcopy
AGC
Colposcopy
Endometrial
sampling
Endocervical
sampling

25. Colposcopy
• Colpus means vagina
• Scope means to see
• So it means to see and magnify the vagina for examination
• Aim
• To magnify the cervix in order to obtain biopsy from suspicious areas
• Aim to define suspicious areas for biopsy

26. Steps
Insert speculum into the vagina
Remove any mucus by swab
The instrument is placed outside the vagina and directed toward the interior of the vagina
Then stain the cervix with acetic acid or Lugols iodine
Then wait till it work
Then suspicious areas detected to take biopsy from it
Biopsy sent for the lab for histopathology examination

27. Different stain types in colposcopy
Acetic acid 5%
• Left over the cervix for about 30
to 60 seconds
• Acetic acid dehydrates epithelial
cells and dysplastic cells with
large nuclei will reflect light and
appear white
• So acetowhite areas are
suspicious and need to be
biopsied
Lugols iodine
• Normal cells stain brown with it
as they contain abundant
glycogen which stain brown with
Lugols iodine
• Suspicious cells stain yellow as
they don’t contain glycogen

28. Suspicious cervix with colposcopy stains
Acetowhite areas with acetic acid stain Yellow areas with Lugols iodine stain

29. The next step is to take biopsy from the
suspicious areas
Satisfactory colposcopy
• This term is given when the
entire TZ is examined during
colposcopy
• Then a colposcopy directed
biopsy is taken from acetowhite
and iodine yellow areas
Non satisfactory colposcopy
• This term is given when the
entire TZ cannot be examined
during colposcopy
• So here cone biopsy or LEEP,
LLETZ will be done
• Also endocervical curettage is
performed

30. Biopsy will be sent for histopathology
Biopsy
results
CIN 1
Cytology was LGIL
Usually regress
Just follow up every 6 months
Regress Back to screening program
Progress or persist Treat as CIN 2
Cytology was HGIL Manage as CIN 2 or 3
CIN 2 or CIN 3 Ablation or excision procedure
Young
Well circumscribed lesion Ablation
Wide local spread Wide local excision
old Wide local excision

31. Methods for treatment of CIN
Ablative methods
• Treat CIN but don’t offer further
diagnostic information
• They include
Cryotherapy
CO2 laser ablation
Excisional methods
• Treat CIN and offer further
diagnostic information
• They include
Loop electrosurgical excision
procedure (LEEP)
Large loop excision of the
transformation zone (LLETZ)
Cold knife conization
CO2 laser conization

32. Why not to do hysterectomy for treatment of
CIN?!
• Hysterectomy isn’t needed as a 1st line treatment for CIN, it is unnecessary
• Even if high grade dysplasia is present, conization must 1st be done to rule out underlying
invasive cancer that may require more advanced procedures such as radical
hysterectomy, radical trachelectomy and lymph node dissection

33. Follow up after
treatment of CIN
Rate of recurrence after treatment
of CIN 2 or 3 is 5% to 17% with no
upper hand for any treatment
modality over the other

34. • CIN is a step before cervical cancer so
detection early is needed to prevent cervical
cancer
• Pap smear is only screening test not
diagnostic test
• Colposcopy is done after abnormal pap tests
• Colposcopy is done to define areas for biopsy
• Histopathology is the diagnostic for CIN
• Hysterectomy isn’t required for treatment of
CIN
Take home
message