The implications of HPV immunisation on cervical screening

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1 The implications of HPV immunisation on cervical screening Dr Maggie Cruickshank Senior Lecturer in Gynaecology Scottish Cervical Cancer Prevention Programme (SCCPP) funded by CSO

2 Cervical screening Detects Pre cancerous changes Cervical intraepithelial neoplasia (CIN) For unimmunised women screening remains the most effective way to reduce their risk of cervical cancer Screening remains important for all women as immunisation does not protect against all HPV types

3 Vaccine Uptake 11% adolescents (13 17years) reported receiving all 3 doses in US (the US Centers for Disease Control and Prevention (CDC) March 2010

4 HPV vaccine uptake in Europe Out of 40 European countries Denmark, Germany, Greece, Italy, Luxembourg, Portugal, Spain and the UK offer HPV vaccination free of charge to at least one age cohort of females Belgium and France offer HPV vaccination on a subsidised basis

5 HPV Vaccine Uptake Figures (reports to 10/08/09) st dose 2nd dose 3rd dose Routine S2 Catchup S5 Catchup S6 Catchup school leavers percentage uptake first dose second dose All three Scotland England Wales N Ireland Scottish data Country data Routine S2 (29,286 in cohort) Catch-up cohorts at school (S5 & S6; 37,954 in cohort) School leavers catch-up (36,381 in cohort)

6 Colposcopy Combination of features = colposcopic impression Subjective procedure Target biopsies and identify abnormal TZ for treatment

7 Colposcopy Combination of features = colposcopic impression Subjective procedure Target biopsies and identify abnormal TZ for treatment HPV16 causes more definite colposcopic abnormality than other HPV types 1 HPV 16 associated with larger size of lesion and visibility of TZ 2 1. Jeronimo J, Massad S, Schiffman M. Visual appearance of the uterine cervix: correlation with human papillomavirus detection and type. Am J Obstet Gynecol 2007; 197:47.e1 47.e8. 2. Louwers JA. Kocken M. van der Bijl JC. Berkhof J. Snijders PJ. Meijer CJ. Verheijen RH. Colposcopic characteristics of high risk human papillomavirus related cervical lesions. Journal of Lower Genital Tract Disease 2010; 14(1):49 55.

8 Colposcopic impression or histology at initial colposcopy Biopsy and Recall Immediate LLETZ Normal colposcopy 40% 49% No CIN 27% 16% CIN 1 17% 14% CIN 2 8% 10% CIN 3 8% 10% TOMBOLA Group: Cotton S, Sharp L, Little J, Cruickshank M, Seth R, Smart L, Duncan I, Harrild K, Neal K and Waugh N. The role of human papillomavirus testing in the management of women with low-grade abnormalities: multicentre randomised controlled trial. BJOG 2010;117(5).

9 Histological outcome and management performed by HPV status Normal No CIN CIN1 CIN2/3+ Punch biopsy LLETZ RR Punch biopsy LLETZ RR Punch biopsy LLETZ RR Punch biopsy LLETZ RR HPV+ 33% 35% % 11% % 17% % 38% 1.41 HPV- 44% 58% % 20% % 13% % 9% 1.13

10 Colposcopic impression and histological outcome by management and by HPV status Normal TZ No CIN CIN1 CIN2/3+ Punch biopsy LLETZ RR Punch biopsy LLETZ RR Punch biopsy LLETZ RR Punch biopsy LLETZ RR HPV +ve 33% 35% % 11% % 17% % 38% 1.41 HPV -ve 44% 58% % 20% % 13% % 9% 1.13

11 How will HPV vaccines change colposcopy? Do certain HPV genotypes cause a specific colposcopic appearance? Could this impact on interpretation of colposcopy findings? Could this impact on ability of the colposcopist to identify lesions to target biopsies? Could this impact on ability of the colposcopist to perform conservative treatments that only treat the abnormal transformation zone?

12 SCCPP colposcopy and HPV genotyping study Women aged years old particiapting in the Scottish cervical screening programme who are referred to colposcopy with an abnormal smear Sample of HPV genotyping Data on colposcopic features 2010 pre immunisation 2012 post immunisation

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14 Referral Cytology

15 Definitive outcome postcolposcopy

16 HPV infections

17 High risk HPV Genotypes HPV Genotype Frequency (%) HPV HPV HPV HPV HPV 52 18

18 Colposcopic Opinion and HPV genotype HPV 16/18 Other HPV types Normal 25% 42% Low grade CIN 39% 33% High Grade CIN 36% 25%

19 Colposcopic Opinion, Histology and HPV genotype HPV 16/18 Other HPV types Normal 25% 42% Low grade CIN 39% 33% High Grade CIN 36% 25% CIN2/3 47% 17%

20 Positive predictive value of Colposcopic opinion of high grade CIN and HPV genotype HPV 16/18 Other HPV types PPV 85% 50%

21 What do we need to know?

22 2015 Continue with primary prevention by HPV immunisation Withdraw secondary prevention by cervical screening Primary HPV screening +/ triage Cytology Molecular markers Other

23 Colposcopy after 2015 Removed for screening programmes Attrition of colposcopy service Non specialist service Ultra specialist service Loss of clinical effectiveness Low prevalence of disease Non16/18 HPV types

24 Colposcopy after 2015 Refinement and re definement of colposcopy practice Recognition of colposcopic features New referral populations Selection of referral to colposcopy Increased specificity of screening tools Use of new technologies based on physical properties of CIN

25 Colposcopy after 2015 Refinement and re definement of colposcopy practice Second phase of genotyping with immunised women 2013 Selection of referral to colposcopy mrna testing Other markers Use of new technologies DySiS Epitheliometer

26 Further Research Cervical Screening Colposcopy High uptake of vaccine Recruitment Evaluate colposcopy In immunised women With improved case selection With alternatives to colposcopy