This document discusses guidelines for the management and treatment of cervical intraepithelial neoplasia (CIN). It states that treatment should be based on an assessment of all case characteristics, not just test results, and aim to reduce cancer risk while minimizing side effects. For CIN3, treatment usually involves counseling, colposcopy, and excision of the entire transformation zone. Destructive methods may be used in some cases but excision allows histological examination. Larger excisions of type 2 or 3 transformation zones carry a higher risk of incomplete margins. While success rates are high, excision can increase risks of preterm birth, especially for larger specimens. Treatment should be tailored based on individual risk factors and fertility desires

1. FOGSI / FIGO
2013
Hydrabad
THE MANAGEMENT OF CIN
wprendiville

2. The management of CIN
• Should read The management of
women with CIN
• Should never be dictated by an
individual test result, even histology
• Should incorporate all the case
characteristics
• Is a balance of benefit vs harm

3. How to safely treat CIN3
• Safely means
– Reducing the risk of cervical cancer to
almost zero
– Reducing the side effects of treatment to
as low as possible

4. The management of CIN3
• Will always include
– Pre-treatment counselling
• Need for Rx, risks of Rx, need for follow up
monitoring by cytology/HPV/Colposcopy
– Assessment of all the case characteristics
• Age, parity, future fertility, likelihood of default,
cytology, histology, HPV status and other
biomarkers where known.

5. Safe treatment of CIN3
• Will always mean
– A preliminary colposcopic examination
• By a trained colposcopist
• Documenting specific findings
– If excisional, Rx will be colposcopically
guided
– Eradication of the entire TZ
– Sufficient tissue for histology to rule out
invasive or associated GIN

6. Safe treatment of CIN3
• Will sometimes mean
– That excision is necessary
– Removal of a relatively large amount of
cervical tissue
– An associated increased risk of pre-term
labour

7. Safe treatment of CIN3
• May sometimes
– Be performed at the first / assessment visit
– Be performed using a destructive method
– Be performed under general anaesthesia
– Be deferred

8. Choice of treatment for CIN
EXCISIONAL DESTRUCTIVE
Hysterectomy Radical diathermy
Conebiopsy(Varietyoftechniques) Cryocautery
LLETZ type1
LLETZ type2
LLETZ type3
Cold (orthermal)coagulation
Laser excision Laser ablation

9. Destructive methods of
treatment
Advantages
Simple, cheap,
Equipment widely
available
Very effective in expert
hands,
No expense of
histology of TZ
Disadvantages
No histological
examination of TZ.
Concern about the
margins, the true
diagnosis and the
depth of excision

10. Preconditions for ablative
therapy for CIN
The TZ must be fully visible
There must be no cytological or colposcopic
suspicion of invasive disease
There must be no cytological or colposcopic
suspicion of glandular disease
There should be no disparity between
cytological and histological diagnosis
The patient must not have had previous
therapy for CIN

11. Indications for treatment
As ever, a balance of risks
1. Risk of not treating the condition
Progression to cancer
ie ; 50% for CIN 3, perhaps 1% for CIN 1
2. Risk of treating the condition
Short term morbidity, uncommon
Long term complications in particular pregnancy
related, if large type 2 or 3 TZ

12. Threshold for treatment
• High grade disease
– Virtually all CIN 3
– Most CIN 2
• High risk patient with persistent low grade
disease
– Smoker
– Older
– High default risk
– Anxious
– HPV and other biomarker test results

13. EXCISION OF THE TZ
• Hysterectomy is rarely appropriate
– Genuine risk of inadequately treating
invasive disease
– Unnecessary risk of general anaesthesia
and major surgery and no benefit to patient
– May miss VAIN

14. EXCISION OF THE TZ
• Laser excision is entirely reasonable
– Expensive
– Useful for vaginal disease
– Similar success and complications profile
to LLETZ, with perhaps an increased risk
of subsequent perinatal mortality

15. EXCISION OF THE TZ
• LLETZ
– Usually an outpatient procedure
– Relatively inexpensive
– Simple to perform
– Accommodates all cases of CIN and
Microinvasive disease and glandular
disease
– Needs modification according to
presentation
If performed inexpertly may be associated
with excess morbidity

16. Optimising the treatment
experience
• Informed, comfortable, relaxed
• TZ has adequately analgesia
• Privacy, support, confidence
• Appropriately sized suction-
speculum

17. Excision of the TZ
LLETZ
• Under binocular colposcopic vision
• Thoroughly anaesthetised TZ
• After full colposcopic exam
• Low magnification

18. Full colposcopic exam
• Size and Type of TZ
• SWEDE score
• Diagnostic impression of worst lesion
• Documented using ifcpc nomenclature

19. LLETZ
LLETZ using a Tan Loop
2 x 2.5cms
Applicable to wider type 1 TZs
Dental syringe systemused for all LLETZ
procedures
Octapressin and citanest with a 2.2m. Vial and a 27 gauge needle

20. Excision: Principles of
treatment
• Treat the entire TZ
• Excise only the TZ
• Miminise the artefactual damage
– Fulguration not dessication
– Paint the wound with electrosurgery
– Always have monsel’s paste available

21. Excision: Principles of
treatment
• Always, always treat under binocular
colposcopic vision
• Always ensure full vision of :
– the entire TZ
– the entire loop
– and the adjacent vaginal wall
• Pass the loop slowly from left to right

22. Principles of treatment
• Choose the appropriate loop for the
specific TZ
• Modify the technique according to the
TZ type
• Ensure excision of the scj
• Beware the type 3 TZ

23. Type I
• Completely
ectocervical
• Fully visible
• small or large
Transformation Zone
Classification

24. Type II
• has endocervical
component
• Fully visible
• may have
ectocervial
component which
may be small or
large
Transformation Zone
Classification

25. Transformation Zone
Classification
Type III
• has endocervical
component
• is not fully visible
• may have ectocervical
component which may
be small or large

26. Excision Types
new IFCPC proposal
• Type 1 Excision
– Resection of a type 1 TZ
• Type 2 Excision
– Resection of a type 2 TZ
• Type 3 Excision
– Resection of a type 3 TZ
– Glandular disease
– Suspected microinvasion
– Repeat treatment

28. Cases which require a type 3
excision
• CIN with a type 3 transformation zone
• Suspected microinvasive disease
• Suspected glandular disease
• Residual disease, ie previous treatment

29. Long loop or straight wire for
electro-surgicaltype 3 transformation
zone

30. Type 3 TZ
Type 3 excision =
approximately to a
Cone biopsy
LLETZ using a
single large (blue)
loop

31. Excision of a type 3 TZ
• Using a long loop
• Loop dimensions
dictated by
– TZ size
– cervical size
– patient future
– pregnancy
expections
– anticipated grade of
disease

32. Type 3 TZ
Type 3 Excision
approximates to a
Type 3 TZ
Using a straight wire

33. Type 3 TZ
Type 3 Excision
approximates to a
Cone biopsy
Using a straight wire
ie SWETZ

34. Type 3 Excision
• Parous woman, family complete,
• V large type 3 TZ, suspicion of CIN3

35. Success of treatment
Martin-Hirsch PL, Paraskevaidis E, Kitchener H.,
Surgery for cervical intraepithelial neoplasia.
Cochrane Database Syst Rev. 2000;(2):CD001318.
• Published cure rates are very high no
matter which technique is examined
• Success is measured in surrogate ways
• Cure ultimately means the woman will
not develop cancer

36. Laser Ablation Com pared With Loop Excision
Residual Disease: All Grades of CIN
Graph of Relative Risks
Alvarez (375)
Dey (285)
Gunasekera (199)
Mitchel (251)
Meta-analysis
.
0 0.1 1 10 100
favours favours
Loop Excision Laser Ablation
NO SIGNIFICANT DIFFERENCE FOR ALL METHODS
FOR ALL GRADES OF DISEASE
CRYOTHERAPY SHOULD NOT BE USED FOR HIGH GRADE DISEASE
Meta-analysis

37. Success of treatment
• Surprisingly few large RCTs
– No difference between techniques in terms
of success
– except cryocautery

38. Excision
• Margin Status
• Volume excised
• TZ type
• These three aspects of excision will
inform both doctor and patient in terms
of prediction of success and morbidity

39. Margin Status
• Marker for risk of residual disease
– Cytological suspicion 5 - 51%
– Histologically proven 3 - 7%
• Negative margins don’t preclude risk of
residual disease

40. Margin status at excision
• Ghaem-Maghami et al
• Meta-analysis 35,109 subjects
• Recurrence rate, high grade
– Complete excision 3%
– Incomplete excision 18%

41. The relation of type of excision and clear
histopathological margins after LLETZ
Dimitriou E., Martin M., Farrar K & Prendiville W.
• 1071 women who
underwent LLETZ
between January 2004
and October 2008

42. The relation of type of excision and clear
histopathological margins after LLETZ
Dimitriou E., Martin M., Farrar K & Prendiville W.
Small type 1 vs large type 2
RR=1.92 95%CI 1.19-3.08
Small type 1 vs large type 3
RR=3.41 95%CI 1.83-6.37
0%
20%
40%
60%
80%
100%
Small
TZ1
Large
TZ2
Large
TZ3
complet
e
pos
ecto
pos
endo

43. The relation of type of excision and clear
histopathological margins after LLETZ
Dimitriou E., Martin M., Farrar K
& Prendiville W 2009.
• Large type 2 or 3 TZ excisions are
associated with an increased risk of
incomplete excision margin status
• Perform larger TZ excisions in these
circumstances and counsel
appropriately

44. Complications after LLETZ
• Short term morbidity low
• Recent reviews have examined long
term complications, specifically
pregnancy related morbidity
– Kyrgiou et al,Lancet 2006
– Arbyn et al BMJ, 2008

45. Risk of perinatal death by
technique of excision
• Estimate of one perinatal death for
every 70 pregnancies in women treated
by CKC, laser cone or RD compared to
one in 500 for women treated by LLETZ

46. Severe pregnancy related
outcomes Arbyn et al 2008
• The current meta-analysis demonstrates that
CKC and probably also LC and radical
diathermy place women at increased risk of
PM and other serious pregnancy outcomes.
LLETZ and Laser ablation do not.

47. Morphological damage after excision
• Biologically plausible
• Perhaps related to extent or amount of
excision
• Applies largely to cases where ablation
would be inappropriate
– Large type 2 or 3 TZ,
– Previously treated patients,
– Glandular or suspected Microinvasion

48. 48
Preterm delivery (<37W): Excision vs no treatment ~heigth
Height < 10mm
Risk ratio
.1 .2 .5 1 2 5 10
Risk ratio (95% CI)
Raio, 1997 0.52 ( 0.06, 4.83)
Sadler, 2004 0.99 ( 0.57, 1.72)
Samson, 2005 3.02 ( 1.65, 5.53)
Nohr, 2007 0.83 ( 0.21, 3.25)
Overall 1.32 ( 0.59, 2.95)
Risk ratio
.1 .2 .5 1 2 5 10
Raio, 1997 4.64 ( 1.20, 17.88)
Sadler, 2004 1.64 ( 1.13, 2.37)
Samson, 2004 3.84 ( 1.66, 8.88)
Nohr, 2007 2.46 ( 1.45, 4.16)
Overall 2.39 ( 1.55, 3.69)
Height >= 10mm
Risk ratio (95% CI)

49. Risk of preterm labour after
LLETZ
Does size matter?
A retrospective study
Khalid S, Dimitriou E & Prendiville W
BSCCP (poster) 2009

50. Excision dimensions and preterm labour
Khalid S, Dimitriou E & Prendiville W 2009
• 1999 - 2002
• Obstetric & Colpo
databases
• 353 pregnancies in
women after LLETZ

51. Excision dimensions and preterm labour
Khalid S, Dimitriou E & Prendiville W 2009
Increased risk of
preterm labour if
specimens larger
than 6 cubic cms
RR 3.17, 95%CI 1.56 -
6.38

52. Excision dimensions and preterm labour
Khalid S, Dimitriou E & Prendiville W 2009
Increased risk of
preterm labour if
specimens thicker
than 12 mms
RR 3.05, 95%CI 1.37 -
7.08

53. Choices in treatment
• Depends on the case characteristics
– Age, parity, contraception
• Nulliparous 27yr old, minimum risk of default
with a moderate cytological and colposcopic
abnormality
• Sterilised parous 24 yr old with a moderate
cytological and colposcopic abnormality

54. In summary
• Define your treatment threshold
• Always treat under colposcopic vision
• Excise the entire TZ preferably as one
piece
• Minimise the excision of normal tissue
• Minimise morbidity of wound
managment

55. The BSCCP
invites you to the
15th World
Congress
On behalf of
IFCPC
In London
26-30th May 2014
www.IFCPC2014.c