Call Girls Budhwar Peth 7001305949 All Area Service COD available Any Time
rushali ppt (2).pptx
1. HSIL and LSIL
(High grade squamous
Intraepithelial lesion and
low grade squamous
intraepithelial lesion)
Moderator: Dr. Praharshitha
By-Dr.Rushali.
2. Cervical Anatomy
The cervix is composed of columnar
epithelium, which lines the endocervical
canal, and squamous epithelium, which
covers the ectocervix . The point at
which they meet is called the
squamocolumnar junction (SCJ)
The SCJ is not restricted to the external
os. Instead, it is a dynamic point that
changes in response to puberty,
pregnancy, menopause, and hormonal
stimulation .
At menarche, the production of estrogen
causes the vaginal epithelium to fill with
glycogen. Lactobacilli act on the
glycogen to lower the pH, stimulating
the subcolumnar reserve cells to
undergo metaplasia.
3. Metaplasia advances from the original SCJ
inward, toward the external os and over the
columnar villi to establish the transformation
zone.
The transformation zone extends from the
original SCJ to the physiologically active SCJ,
a.
As the metaplastic epithelium in the
transformation zone matures, it begins to
produce glycogen and eventually resembles the
original squamous epithelium, both
colposcopically and histologically
CIN typically originates in the transformation
zone at the advancing SCJ.
4. The entire SCJ with
early metaplastic cells is
susceptible to oncogenic
factors, which may
cause these cells to
transform into CIN.
Changes associated with
CIN are most likely to
begin either during
menarche or after
pregnancy, when
metaplasia is most
active.
Conversely, after
menopause a woman
undergoes little
metaplasia and is at a
lower risk of developing
CIN from de novo human
papillomavirus (HPV)
infection.
5. Human Papilloma Virus
HPV is a non-enveloped double-stranded DNA virus within the Papillomaviridae
family.
The relative risk for developing cervical cancer with high-risk HPV (HR-HPV) is
greater than 70 as compared to less than 5 with other risk factors such as
smoking, high parity, prolonged use of oral contraceptives, and other sexually
transmitted infections.
The cytologic changes of HPV were first recognized by Koss and Durfee in
1956 and given the term koilocytosis .
Specific high-risk HPV types account for about 90%of high-grade
intraepithelial .lesions and cancer (HPV-16, -18, -31, -33, -35, -39, -45, -51, -
52, -56, -58, -59, and-68).HPV-16 is the most common HPV found in invasive
cancer and in CIN2 and CIN 3
6. Pathophysiology of HPV
HPV infects the basal epithelial cells of the transformation zone after gaining
entry through micro-abrasions
A class of cell surface receptors on the keratinocytes called Heparan sulfate
proteoglycans (HSPG) are thought to be the initial receptors for the virus,
attaching to L1 of the capsid.
Entry of the viral genome into the nucleus occurs through nuclear membrane
breaks. Viral replication then begins.
Expression of the L1 and L2 capsid proteins occurs to enable assembly of viral
particles, which are sloughed off along with the dead squamous cells,
allowing continued transmission and infection of the virus.
High-risk HPV types, especially HPV16, have been shown to often integrate
their genome into the human genome. Integration has been proposed as an
early event in the progression of LSIL to HSIL
Viral oncoproteins E6 and E7 maintaining double strand breakpoints in host
DNA by attenuating the DNA damage response (DDR)
7. The high-risk HPV E6
oncoprotein is known to
interfere with p53, a cellular
tumor-suppressor protein
High-risk HPV E7 oncoprotein
inactivates members of the
retinoblastoma (Rb) tumor
suppressor protein family.
As the HPV genome is double-
stranded and integrated into
the host genome, it effectively
evades the immune response
leading to persistent infection.
8. FOGSI GCPR Guidelines for screening
The three main screening modalities are human papillomavirus (HPV)
testing, cytology (Pap smear) and VIA (Visual inspection by acetic acid).
FOGSI recommends the use of HPV testing as the best method for
cervical cancer screening
It recommends screening in hysterectomized women in case of previous
history of CIN and if hysterectomy HPE confirms CIN – need of screening
with HPV at 6 and 18 months.
Screening of immunocompromised female (HIV positive ) should start at 1
st year od diagnosis irrespective of age , repeat every 3 yearly upto the
age of 65.
Pregnant women should undergo speculum examination at first visit if
normal clinically should defer screening till postpartum period (6 weeks).
10. Frequency Primary HPV testing or co
testing every 5 years
Cytology every 3 years
Every 5 years
( atleast 1-3 times in
a lifetime
Age to stop (
years)
65 with consistent negative
results in last 15 years
Women with no prior
screening should
undergo one test at
age of 65 if negative
should exit screening.
Follow up after
treatment
HPV testing (preferred) or
cytology every 12 months
Screening following
abnormal report
irrespective of method of
treatment – 20 years
VIA 12 months
11. HPV Testing in screening
WHO recommends HPV DNA detection as primary screening test.
2 approaches recommended by WHO
1. Screen and treat Approach: Treat all HPV positive women.
2. Screen , triage and treat Approach: After HPV positive result ,
partial genotyping, colposcopy, VIA or cytology is used to triage
women and later treatment plan is advised.
WHO recommends regular cervical cancer screening begin with age of
30 .
Regular screening interval of every 5 to 10 years using HPV DNA as
primary screening test.
After age of 50 screening can be stopped if 2 consecutive negative
results.
12. PAP test
A Papanicolaou test is preferred initial method of screening for
cervical neoplasm.
This is performed by opening vaginal canal with speculum fully
visualizing cervix and using cervical broom or spatula to
exfoliate cells from the transformation zone and transferring
cell into liquid preservative (liquid based cytology ) or
conventionally directly on microscope slide.
The Pap test, was successful in reducing the incidence of
cervical cancer by 79% and the mortality by 70%.
The sensitivity of the cervical cytology for the detection of CIN
2 or 3 ranged from 47% to 62% and the specificity ranged from
60% to 95%.
13. Squamous intraepithelial lesion
SIL encompasses a spectrum of squamous cell lesions starting from the
precancerous lesions of low-grade dysplasia associated with transient
human papilloma virus (HPV) infection to higher grade lesions,
including cervical intraepithelial neoplasia 2 and 3 (CIN 2 and 3) and
ultimately invasive squamous cell carcinoma.
LSIL is now recommended to be used as a diagnostic category to
describe HPV transient infection-related changes, while HSIL is used to
categorize true precancerous lesion.
Some equivocal morphological features suggestive of squamous cell
abnormality may fall under equivocal category: “Atypical Squamous
Cells” (ASCs), which are subdivided into two categories; “Atypical
Squamous Cells of Undetermined Significance” (ASC-US) or
“Atypical Squamous Cells, HSIL cannot be excluded” (ASC-H),
14.
15. Low grade squamous intraepithelial
lesion
About 1.7% of all PAPs are interpreted as LSIL,
the majority of which (>80%) are positive for
HR-HPV
LSIL lesions are found in women 10 years
younger than those with invasive cancer.
LSIL cases are caused by a transient self-limiting
HPV infection that usually lasts less than 2
years.
On the other hand, persistent infection carries
higher risk of progression to neoplastic
transformation.
Major cytomorphologic and an easily identifiable
feature of LSIL is koilocytosis.
Koilocytes show raisinoid nuclei with sharply
delineated perinuclear cytoplasmic clearing
with irregular outline including focal angulations
16. Enlargement of the nuclei, 3 times the size of
Intermittent Cell Nuclei, is important feature of
LSIL cells.
Multinucleation with 2–3 nuclei may be seen.
The chromatin is very dark with raisinoid
appearance
May show increased keratinization
Differential Diagnosis:
1) Parakeratosis : can be seen in the background
of infections including an HPV infection.
2) Psuedokoilocytosis: only tight perinucleolar
halos seen. Common in infection like candida,
trichomonas and atrophic
3) Glycogenated “navicular” cells: perinuclear
space occupied by yellow tinged “glycogen”.
4) Herpes simplex viral cytopathic effects :
Chromatin margination give ground glass
appearance of cells.
5) Radiation changes: enlargement of both
Nucleus and cytoplasm.
17. High grade squamous intraepithelial
lesion.
It encompasses the previously used terms of CIN2, CIN3, moderate and severe
dysplasia and carcinoma in situ.
Long-term progression to invasive cancer is estimated at 30% for 30 years.
About 0.3% of all PAPs are interpreted as HSIL, almost all (95%) of which are
HR-HPV positive.
Cytomorphological features of HSIL cells:
1. Singly scattered HSIL cells, as sheets with checkerboard pattern or in
syncytial aggregates of HCG
2. HSIL cells are smaller and show less cytoplasm than cells of LSIL
3. High N/C ratio compared to LSIL
4. Irregular nuclear contours with frequent indentations and longitudinal nuclear
grooves
18. Increased mitotic index and
abnormal mitotic figures,
especially within more
superficial layers of the
epithelium.
Decreased organization from
the lower immature cell layers
to the superficial mature layers
(loss of polarity)
Usually hyperchromatic nuclei,
evenly distributed coarse
chromatin
Cytoplasm is variable from
“immature” dense
“metaplastic” with focal
vacuolation to occasionally
densely keratinized cytoplasm
19. ATYPICAL SQUAMOUS CELLS (ASC):
A) ASC-US (ASCs of undetermined
significance):
Enlarged nuclear size 2.5–3 times ICN
Mild increase in N/C ratio
Mild hyperchromasia and nuclear irregularity
Atypical parakeratosis with orangeophilic
cytoplasm and equivocally atypical nuclei
Atypical repair with “School of Fish”
streaming pattern with prominent nucleoli.
20. B) ASC – H :
Nuclear size 2.5–3 times
ICN
Mild increase in N/C ratio
Mild hyperchromasia and
nuclear irregularity
Other features overlapping
with HSIL but not
unequivocal
23. .
As its not a cancer Precursor spontaneous regration rate is
60% - 85% Hence option of Cytology every year for 2 years
is advised.
If after within 2 years cytology is negative usual screening
is continued.
If after 2 years Cytology is still positive for LSIL, option of
transformation zone with ablation or excision is given.
24. Colposcopy
Colposcopic assessment is a critical component of the
follow-up of the abnormal cervical screening.
Women with HSIL on Pap smear are recommended to
undergo Colposcopy.
Acetowhite epithelium : Epithelium that turns white
after application of acetic acid (3% to 5%)
The acetic acid does not affect mature, glycogen-
producing epithelium because the acid does not
penetrate below the outer one-third of the epithelium.
The cells in this region have very small nuclei and a large
amount of glycogen (not protein). These areas appear
pink during colposcopy.
Dysplastic cells are those most affected. They contain
large nuclei with abnormally large amounts of chromatin
(protein). The columnar villi become “plumper” after
acetic acid is applied, making these cells easier to see.
They appear slightly white, particularly in the presence
of metaplasia.
25. Aims of colposcopy
To study cervix when Pap smear is abnormal
To locate area and take biopsy
To study extent of abnormal lesion
Punch biopsy and excisional cone biopsy to provide tissue for
histopathological confirmation.
Conservative surgery under colposcopic guidance like
a)electrocoagulation- temperature over 70 degree Celsius
destroy tissue upto 8- 10 mm
B) laser ablation: boils, steams or explodes cells- destroys
tissues upto 5mm.
27. ACETO
UPTAKE
0
Zero or
transparent
1
Shady milky,
Neither
transparent nor
opaque
2
Distinct
opaque
white
Margin/surfa
ce
diffuse Sharp and irregular Sharp
includes
cuffing
Iodine
staining
brown Patchy yellow Distinct
yellow
vessel Fine regular absent Coarse or
atypical
Lesion size < 5 cm 5-15 cm or
Two or more
quadrants
15 cm or
Three to
four
quadrants or
undefined
endocervical
ly
Swede Score
If score
0-4 = LSIL
5-6=
HSIL
(non invasive)
7-10 =
HSIL (suspected
invasive lesion)
28. Cryotherapy
Acceptable in following cases :
1. LSIL that has persisted for 24 months or CIN 2
2. Small lesion
3. Ectocervical location only
4. Negative endocervical sample
5. No endocervical gland involvement on biopsy.
Cryotherapy destroys surface epithelium of cervix by
crystallizing the intracellular water . Nitrous oxide -89
degree Celsius and carbon dioxide – 65 degree Celsius
are most commonly used gases.
Freeze Thaw Freeze method is used and an iceball of 5
mm is achieved .
29. Management of HSIL
Women with HSIL cytology are recommended to undergo
colposcopy with endocervical sampling.
If CIN2 or greater is not diagnosed on biopsy, it is
recommended the patient follow-up with cytology and
colposcopy every six months for a 24 month period, as
long as her exams are adequate and reveal no squamous
intraepithelial lesions or at most LSIL.
If the colposcopy is adequate and HSIL (CIN2, CIN3 or
CIN2-3) is confirmed on biopsy, ablation of the
transformation zone or excision is considered acceptable.
Only a diagnostic excisional procedure is acceptable if the
colposcopy is inadequate or the endocervical curettage
shows a high-grade lesion.
30.
31. Loop Electrosurgical Excision
It offers advantage of diagnostic and
therapeutic operation during once
OPD visit.
It’s a treatment for an HSIL cytology.
A) Electrocautery effect : larger
diameter of wire loop and low power(
is used. Causes thermal damage to
tissue .
B) Electrosurgical effect: smaller
diameter of wire loop and high power
(35-55W)
32. Conization
Includes entire outer margin and endocervical lining of internal os.
Conization is indicated for diagnosis in women with CIN 3 or AGC-AIS
and
may be considered under the following conditions:
1. Limits of the lesion cannot be visualized with colposcopy.
2. The SCJ is not evaluable at colposcopy.
3. ECC histologic findings are positive for CIN 2 or CIN 3.
4. Substantial lack of correlation between cytology, biopsy, and
colposcopy results.
5. Microinvasion is suspected based on biopsy, colposcopy, or cytology
results.
6. The colposcopist is unable to rule out invasive cancer.
33. A) Diagnostic conization B)Therapeutic conization
c) LEEP
Complications : bleeding, sepsis, cervical stenosis,abortion,
preterm labour.
34. Hysterectomy
Hysterectomy for HSIL is considered as overtreatment but
following are the indications :
• Older and parous women
• When women cannot comply follow up
• uterus associate with fibroids,DUB or prolapse
• If microinvasion exists
• If recurrence following conservative therapy or persistent
lesion
• Insitu adenocarcinoma of cervix .
35. Characteris
tics
cryoth
erapy
coagulati
on
Laser
ablation
Conizatio
n knife
Laser
conizatio
n
LLETZ LEEP
Place OPD OT OPD OT OT/OPD OPD OPD
complicatio
n
nill bleeding bleeding nill nill
pain nill painful slight slight slight slight
sepsis dischar
ge
discharge - discharge slight slight -
Pregnancy
complicatio
n
nill nill nill Stenosis
abortion
Preterm
labour
stenosis
Depth of
distruction
4-5
mm
8-10 mm 7 mm - - - -
Cure rate 90% 90-95% 90- 97% 90- 97% 90- 97% 90- 97% 90- 97%
36. Reference
Berek and Novaks textbook of gynaecology.
Shaw’s textbook of gynaecology
FOGSI GCPR screening guidelines
www.ncbi.nlm.nih.gov/books
www.ncbi.nlm.gov/pmc
