Management of cervical cancer

1. CERVICAL CANCER
(Cervical Intraepithelial
Neoplasia)
Done By-
Nirmal Sharma
Preethi Chandrasekar
Nivedita S

2. CONTENTS
• Anatomy of Cervix and vagina
• Transformation zone
• Pap Smear and Bethesda classification system
• Risk factors for CIN/CA Cervix
• Human Papilloma Virus
• Colposcopy
• Cryoablation

3. Anatomy of the Cervix and Vagina
Endocervix:
• Supravaginal Part
• Lined by the Mullerian Duct
(ie.Columnar Epithelium)
• Red and Velvety
Exocervix:
• Partio Vaginalis
• Lined by Non Keratinized Stratified
Squamous Epithelium
• Pink and Smooth

4. AT PUBERTY:
Hypothalamo-Pituitary Ovarian Axis
Estrogen
Columnar cells & Squamous cells
Increase in Glycogen
• This glycogen is converted to lactic acid by Lactobacilli which is responsible for the
acidic pH of the vagina.
• Thus the acidic pH acts as a stimulus for Squamous Metaplasia(Replacement of
columnar cells into squamous cell)

5. TRANSFORMATION ZONE:
• Most common site of CA Cervix-
Transformation zone
• Most common type of CA Cervix-
Squamous cell carcinoma (Most
common site is exocervix)
• 2nd most common type of CA
cervix- Adenocarcinoma (Most
common site is endocervix)

6. • This squamous metaplasia is a physiological process that takes place in all females
that takes place in the transformation zone but metaplasia cells are vulnerable for
oncogenic effect of HPV and other oncogenes.
• Squamous metaplasia is most active during adolescence and pregnancy which
means early age of intercourse and 1st pregnancy is a risk factor for CA cervix.
Note:
Columnar epithelium has got glands & ducts
When Squamous metaplasia occurs, these ducts gets blocked
Produces Nabothian Cyst / Nabothian follicles
Marking to differentiate transformation zone
(When pap smear is done and if any lesion/friable mass on cervix is present it should

7. TRANSFORMATION ZONE
(Dynamic area)
Moves towards Exocervix
Moves towards endocervix
Under the influence of Estrogen
Decreased Estrogen
Adolescence
Menopause
Pregnancy
Lactation
Oral combination pills

8. On Per speculum examination, the transformation zone can be classified into three types based
on WHO classification
TYPE
1
• Entire
transformati
on zone is
visible
• Lies entirely
on
TYPE
2
• Transformati
on zone is
visible
• Transformati
on zone has
some
endocervix
component
TYPE
3
• Transformati
on zone is
not visible
• Transformati
on zone
extends into
endocervica
canal

9. DYSPLASIA occurs in oncogenic stimuli
When metaplasia occurs in disorganized manner, it is called dysplasia which is a
premalignant condition
• If dysplasia occurs in < 1/3rd of cervical thickness- CIN 1
• If dysplasia occurs in 1/3rd to 2/3rd of cervical thickness- CIN 2
• If dysplasia occurs in > 2/3rd of cervical thickness- CIN 3
If overlying membrane intact
Cancer insitu
• If dysplasia occurs in the entire thickness
If overlying membrane broken
Invasive cancer

10. PAP SMEAR (Cytological Study)
• With the help of Ayer’s spatula and endocervical brush, we are
taking only the cell. So thickness involved cannot be
appreciated & CIN cannot be diagnosed.
• Pap smear can differentiate only squamous cell abnormality
(or) glandular cell abnormality.
• CIN can be diagnosed only with biopsy
• The Bethesda system is a system for reporting cervical or
vaginal cytological diagnoses, used for reporting Pap smear
results.

11. Bethesda Classification System
Papsmear is
adequate when
In conventional
Papsmear
If number of
squamous cells are
8000 to 12000/10
high power field
Endocervical
cells 10-12
In liquid based
cytology sample
If number of
squamous cells are
5000/10 high power
field
Endocervical
cells 10-12

12. Pap Smear
Squamous cell
abnormalities
•1) Atypical squamous cell
•2) Low grade Squamous
intraepithelial lesion
•3) High grade squamous
intraepithelial lesion
•4) Cancer insitu squamous
cell carcinoma
Glandular cell
abnormalities
1) Atypical glandular cell
2) Adenocarcinoma insitu
3) Adenocarcinoma

13. Conclusion drawn from Pap Smear
LSIL
(Report on Pap
Smear)
• CIN 1 on HPE roughly
HSIL
(Report on Pap
Smear)
• CIN 2&3 on HPE roughly

14. Risk factors for CIN/CA Cervix
1. HPV
2. Early age of intercourse(<18yrs)
3. Early age of 1st pregnancy(<20yrs)
4. Multiple partners
5. Immunocompromised state
6. Multiparity
7. Smoking (leads to squamous cell carcinoma)
8. OCPs (Reversible risk) Risk is more if female has used OCP
>5yrs
It may produce adenocarcinoma or
squamous cell carcinoma
Cancer cervix is not related
with
• Early menarche/Late
menopause
• Genetic/Family history

15. Human Papilloma
Virus
• Double stranded DNA
virus
• Epitheliotropic- For
completion of lifecycle
of HPV, it requires intact
squamous epithelium
because:
o Early genes of HPV (E
gene 1 2 4 6 7) are
expressed in parabasal
and basal layers
o Late genes of HPV (L
gene 1 2) are
expressed in superficial
layer

16. When HPV infects epithelial cells
Produces changes in cells called
“Koilocytosis” including perinuclear
and paranuclear halo
Corresponds to LSIL
So if a female gets report of LSIL,
either she could be having CIN 1 or
Koilocytosis
Genes
of
HPV
E1 & E2- Needed for Viral
replication
E6- Knocks out tumor
suppressing gene p53
E7- knocks out
Retinoblastoma gene
L1 gene- Major Capsid protein
(HPV vaccines are made)
L2 gene- Minor Capsid protein

17. HPV
Low Risk HPV
HPV 6 & 7
(Leads to)
1.1)Genital
warts/Condyloma
2.2)Recurrent
laryngeal papilloma
High risk HPV
HPV 16 18 31 33 45
52 58
(Got Oncogenic
potential)
In females:
CA Cervix
CA Vulva
CA vagina
In males:
CA penis
In both:
Oral cancer
Anal cancer
• Most Common high risk HPV
causing CA cervix is HPV 16
• Most common specific for CA
cervix is HPV 18

18. Transmission of HPV infection
Sexually transmitted
• During intercourse, certain
microabarations can happen
in epithelium that leads to
HPV getting into basal layer
of epithelium
• Applied aspect:
In all females who have
uterus and all transgender
male who have uterus should
be screened for cancer
Congenital HPV infection
• Can occur when a new born
to a female with genital wart
• This infection is transient, so
there in no need for C-
section in pregnant female
with genital wart
C-section should be done only
if warts are so big so they will
obstruct vaginal delivery or
may bleed during delivery

19. Course of HPV infection
Mostly
Spontaneous clearance
Sometimes
Remain latent that later
leads to genital warts
Persist more than 6 months
Later E6 & E7 genes are
expressed that leads to CIN
and later CA Cervix
HPV infection takes 10-30 years to transform into Cancer cervix and thus
screening is important

20. HPV Vaccines
LEVIRAX
Effective against HPV 16 18
Prevents CA Cervix
GARDASIL
Effective against 6 11 16 18
Prevents genital warts and CA
Cervix
GARSASIL-9
Effective against 9 HPV
subtypes
Against all 6 cancers and
genital warts

21. Report of Pap Smear
ASCHS(Atypical squamous cells
of unknown significance)
If age <25yrs then repeat pap
after 1yr
If age >25 then HPV
testing(Reflex test) done and if
positive then colposcopic
directed biopsy done
LSIL(Low squamous
intraepithelial lesion)
If age <25yrs then repeat pap
between 6-12 months
If age >25yrs then colposcopic
directed biopsy done
ASCH(Atypical squamous cell
HSIL- cannot be ruled out)
Colposcopic directed biopsy
with endocervical curettage
HSIL(High squamous
intraepithelial lesion)
Colposcopic directed biopsy
with endocervical curettage
• Based on Pap smear, we are never going to
do treatment.
• If pap smear report is positive then do
colposcopic directed biopsy and then
treatment should be given.

22. COLPOSCOPY
•Magnifying instrument
•OPD procedure
•Can visualize Exocervix but Endocervix
cannot be visualized

23. Procedure:
Take biopsy from rough area and white area
Apply acetic acid(3-5%)
Dysplastic cells has high N:C ratio so proteins in nucleus gets coagulated and appear white in colour
called Acetowhite appearance
Take biopsy from acetowhite appearance also
If it has green filter If there is lesion in endocervix
then do endocervix curettage
Shows abnormal blood vessels Followed by
biopsy/ conisation
• Punctate (include endocervix
exocervix and transformation zone)
• Mosaic
• Reticular If no

24. COLPOSCOPY REPORTS
For CIN 1
• Histologically corresponds to LSIL or HPV changes
• So high chances of spontaneous regression
• Follow-up for 2yrs because most of the cases are
going to regress in 2 yrs.
• If CIN 1 persists more than 2yrs then do Cryoablation
or LEEP

25. For CIN 2 & 3
• Cryoablation
• Excisional procedure
LEEP(Loop electro excisional procedure)/ LLETZ(Large
loop excision of transformation zone)
Conization

26. CRYOABLATION
1. WHO says to do cryoablation if there is no suspicion
of invasive cancer and glandular disease
2. Entire lesion should be visible ie. It should be small
(Limited to two quadrants of cervix)
3. Not useful for treating CIN 3 females with HIV
positive