What is being excised and why? Professor Henry Kitchener Institute of Cancer Sciences The University of Manchester

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1 What is being excised and why? Professor Henry Kitchener Institute of Cancer Sciences The University of Manchester

2 Qu. What is being excised? A. Colposcopic lesions which should contain CIN2+ Qu. Why is it being excised? A. To remove the lesion in its entirety and exclude underlying microinvasion

3 Incomplete excision CIN up to ectocervical margin CIN up to endocervical margin

4 Large Loop Excision of the Transformation Zone Qu. Are loop excisions excessive? A. Very often, yes

5 Surgery for cervical intraepithelial neoplasia Qu. Do these lesions require to be excised? A. No. There are alternative treatments which ablate the lesion; laser and cold coagulation Cochrane review (2014); P. Martin-Hirsch, E Paraskevaidis, A Bryant, H O Dickinson Conclusions:..no obvious superior surgical technique for treating CIN in terms of treatment failure or morbidity (cold coagulation not evaluated, nor pregnancy outcomes) most trials were grossly underpowered High cure rates means RCT s would require several thousand patients to be capable of demonstrating superiority.

6 Number of woman-years of follow-up and invasive cancers, cumulative rate of invasive cervical cancer at end of follow-up, and rate of invasive cancer during follow-up by treatment method and centre Cold coagulation Laser vaporisation Laser vaporisation n % CIN3 Rate of invasive cancer per 100,000 woman years (95% CI) Cumulative rate of invasive cancer per 1000 women (25-145) 7.5 at 8 years (49-158) 8.9 at 8 years (10-76) 2.9 at 10 years Loop diathermy (59-305) 6.5 at 5 years Pooled rate was 5.8 cancers/1000 women after 8 years

7 Pathology of LLETZ 917 women treated between Nov 2001 and Dec 2004 Mean age 31.5 years (range years) CIN2/3 700 (76%) CIN1 217 (24%) 95% treated by LLETZ 77% clear endo margins 72 % clear ecto margins At 6 months: 14.6% were HPV+ve 10.7% were ASCUS+ From Kitchener et al, BJOG (2008)

8 Extended follow up post LLETZ Recruited between May 2002 and June 2005 Cumulative Cumulative Cumulative Cumulative ASCUS+ LSIL+ HSIL+ CIN2+ 24 months (n=745) months (n=614) months (n=317) months (n=261) From Kitchener et al, BJOG (2008)

9 Measurements made on a section from a cervical conization specimen. A = depth of the deepest crypt; B = depth of the deepest involved crypt. Depths of Crypts With and Without Involvement by CIN Grade 3 Crypt status Mean (mm) Maximum (mm) Mean SD (mm) 95% Mean +3 SD (mm) 99.7% Uninvolved Involved

10 Laser ablation Treatment methods for CIN Expensive kit A proportion of failed treatments Precision in width and depth Cold coagulation Cheap kit Straightforward to use Loop excision Cheap kit Some morbidity (bleeding/pain) Lacks precision Histopathology costs

11 Dimensions of LLETZ specimens and margin involvement Margin involvement (n=108) Complete excision Both margins involved Endocervical margin involved Ectocervical margin involved Uncertain (No CIN) 33 (30.6%) 12 (11.1%) 6 (5.5%) 33 (30.6%) 15 (13.9%) (9) (8.3%) Depth (n=108) <1CM 1-1.5CM 1.6CM+ 29 (26.9%) 67 (62.0%) 12 (11.1%) Widest diameter (n=108) <1.5CM 1.5-2CM 2cm> 20 (18.5%) 60 (55.6%) 28 (25.9%)

12 Depth of specimen by grade of CIN Depth Depth 1.5CM >1.5CM <1CM 1CM CIN1/2 (n=64) 59 5 (7.8%) CIN1/2 (n=64) (75%) CIN 2/3+ (n=35) 30 5 (14.3%) CIN 2/3+ (n=35) (68%)

13 LLETZ: Depth by Width (n=108) Width Depth <1.6CM 1.6CM+ <2CM 65 2CM 31 3 (4.4%) 9 (29%)

14 Excision status by specimen width and by CIN grade Grade Width Grade Excision status Widest diameter <2CM Widest diameter 2CM Complete excision (n=33) Excision incomplete/ uncertain (n=66) CIN1/2 (n=64) (30.5%) CIN1/2 (n=64) (60%) CIN 2/3+ (n=35) (42.8%) CIN 2/3+ (n=35) 7 28 (80%)

15 Excision status by specimen dimension (n=99) Excision status Depth Excision status Widest diameter 1.5CM >1.5CM <2CM 2CM Complete excision (n=33) 28 5 (15.1%) Complete excision (n=33) (30.3%) Excision incomplete/ uncertain (n=66) 61 5 (7.6%) Excision incomplete/ uncertain (n=66) (42.5%)

16 Considerations in the need for excision vs. ablation Colposcopy appearance Type 1 Type 2 Type 3?microinvasive Very wide TZ Age Prior to childbearing Post childbearing Balance between the need for depth and width

17 Role of excision Avoid excision in the absence of disease CIN1 is not treated CIN1/2 should be ablated CIN2/3 can be ablated or excised Recurrent or residual disease should be excised

18 Conclusions No compelling reasons to have LLETZ as standard of care for the treatment of CIN Should be used more selectively Type 2/3 cervix CIN3 Suspicion of microinvasion Deep excision (>1.5cm) should be avoided unless clinically indicated Need for improved QA in the use of LLETZ