FOGSI / FIGO

2013

Hydrabad

THE MANAGEMENT OF CIN

wprendiville

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

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

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.

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

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

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

Choice of treatment for CIN

EXCISIONAL DESTRUCTIVE

Hysterectomy Radical diathermy

Cone biopsy (Variety of techniques ) Cryocautery

LLETZ type 1

LLETZ type 2

LLETZ type 3

Cold (or thermal) coagulat ion

Laser excision Laser ablation

Destructive methods of

treatmentAdvantages

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

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

Indications for treatment

As ever, a balance of risks

1. Risk of not treating the conditionProgression to cancer

ie ; 50% for CIN 3, perhaps 1% for CIN 1

2. Risk of treating the conditionShort term morbidity, uncommon

Long term complications in particular pregnancy related, if large type 2 or 3 TZ

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

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

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

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

Optimising the treatment

experience

• Informed, comfortable, relaxed

• TZ has adequately analgesia

• Privacy, support, confidence

• Appropriately sized suction-

speculum

Excision of the TZ

LLETZ

• Under binocular colposcopic vision

• Thoroughly anaesthetised TZ

• After full colposcopic exam

• Low magnification

Full colposcopic exam

• Size and Type of TZ

• SWEDE score

• Diagnostic impression of worst lesion

• Documented using ifcpc nomenclature

LLETZLLETZ using a Tan Loop

2 x 2.5cms

Applicable to wider type 1 TZs

Dental syringe system used for all LLETZ

procedures

Octapressin and citanest with a 2.2m. Vial and a 27 gauge needle

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

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

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

Type I

• Completely

ectocervical

• Fully visible

• small or large

Transformation Zone

Classification

Type II

• has endocervical

component

• Fully visible

• may have

ectocervial

component which

may be small or

large

Transformation Zone

Classification

Transformation Zone

Classification

Type III

• has endocervical

component

• is not fully visible

• may have ectocervical

component which may

be small or large

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

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

Long loop or straight wire for

electro-surgicaltype 3 transformation

zone

Type 3 TZ

Type 3 excision =

approximately to a

Cone biopsy

LLETZ using a

single large (blue)

loop

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

Type 3 TZ

Type 3 Excision

approximates to a

Type 3 TZ

Using a straight wire

Type 3 TZ

Type 3 Excision

approximates to a

Cone biopsy

Using a straight wire

ie SWETZ

Type 3 Excision

• Parous woman, family complete,

• V large type 3 TZ, suspicion of CIN3

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

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

Success of treatment

• Surprisingly few large RCTs

– No difference between techniques in terms

of success

– except cryocautery

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

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

Margin status at excision

• Ghaem-Maghami et al

• Meta-analysis 35,109 subjects

• Recurrence rate, high grade

– Complete excision 3%

– Incomplete excision 18%

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

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

epos

ectopos

endo

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

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

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

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.

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

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)

Risk of preterm labour after

LLETZ

Does size matter?

A retrospective study

Khalid S, Dimitriou E & Prendiville W

BSCCP (poster) 2009

Excision dimensions and preterm labour

Khalid S, Dimitriou E & Prendiville W 2009

• 1999 - 2002

• Obstetric & Colpo

databases

• 353 pregnancies in

women after LLETZ

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

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

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

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

The BSCCP

invites you to the

15th World

Congress

On behalf of

IFCPC

In London

26-30th May 2014

www.IFCPC2014.c

om