Baseline HPV 2009: A route to evaluation of the HPV vaccination programme

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1 Baseline HPV 2009: A route to evaluation of the HPV vaccination programme Dr Sam Hibbitts Senior Lecturer in HPV Department of Obstetrics & Gynaecology School of Medicine Cardiff University

2 Avian Papillomavirus

3 Human Papillomavirus Infection Essential underlying cause of cervical cancer up to 99.7% of invasive cervical carcinomas HPV infection is very common and most infections do not result in cancer 80% all HPV infections are cleared in <1 year High Risk (HR) HPV types linked with neoplasia development types 16 and 18 account for more than 70% of all cervical cancers Low Risk (LR) HPV associated with genital warts

4 HPV Prevalence (%) Human Papillomavirus Prevalence Worldwide HPV is found in 10.4% women with normal cytology Geographical highest levels detected in Africa (22.1%) lowest in Asia (8.0%) South Wales Prevalence Study HR-HPV LR-HPV Age: highest levels in women aged 35 or less Age (Years)

5 Major Steps in Cervical Cancer Development

6 HPV Infection Mature Squamous Squamous Supra-basal L1 and L2 Basal cells Basement Membrane E1, E2, E5 E4, E6, E7 Epithelial cell cycle Low grade Lesion HPV gene expression

7 Prophylactic HPV Vaccination Simple structure, based on L1 capsid protein Quadrivalent: HPV 16, HPV 18, HPV 6 and HPV 11 Bivalent: HPV 16 and HPV 18 Virus Like Particles (VLP) Spontaneous assembly

8 In October 2007 recommendations were announced that all 12 to 13 year olds would be offered the HPV vaccine from September In June 2008 the Government announced that the bivalent vaccine Cervarix TM (GSK) would be implemented (3 year tenure).

9 HPV Vaccination Update in Wales: Area (LHB/ULHB) Girls (n) 14 years 19 years Percentage (%) 1 dose 2 doses 3 doses Girls (n) Percentage (%) 1 dose 2 doses 3 doses ABM Anueurin Bevan Betsi Cadwaladr Cardiff & Vale ULHB CWM Taf Hywel Dda Target Group 1 st dose 89.7% 2 nd dose 89.1% 3 rd dose 86.6% Catch-up Group 1 st dose 48.8% 2 nd dose 42.9% 3 rd dose 31.8% Powys Teaching Wales Total PHW Cover quarterly Report June 2010

10 Long Term Objectives To monitor changes in HPV type specific prevalence following the implementation of prophylactic HPV vaccination in Wales Cohort 1: Baseline Cohort 2: Catch-up Cohort 3: Target

11 Advantages in Wales Cervical screening starts at age 20 years National databases held within a single NHS Trust Immunisation records Cervical screening results Cancer incidence

12 Key Questions How effective is the vaccine in reducing the targeted HR types (HPV 16/18)? Is there cross-protection? Is there type replacement? Is uptake of cervical screening affected? What are the effects of the vaccination programme on cervical cytology results (all grades), CIN lesions and cervical cancer cases?

13 Baseline HPV 2009 Cancer Research Wales

14 Cohort 1: Study Aim Characterise HPV infection in Wales in cervical smears from young women: aged years who have not been offered the HPV vaccine are attending for first routine cervical smear

15 Infrastructure Cervical Screening Wales Following current standard operating procedures and guidelines HPV Research Labs Following current standard operating procedures and guidelines Study Population All women who attend for 1 st routine cervical smear (20-22 yrs) in Wales Samples transported each week Residual smears assigned a unique study code Routine cytological analysis Residual smears flagged and patient ID removed Excel data sheet generated linking cytology lab ID with unique study code Cervical Screening Administration Department for reporting results Data transfer Study code linked with cytology, age and social deprivation score HPV genotyping and data analysis Patient management according to current guidelines Profile of HPV prevalence

16 Samples Received (n=15,342) Cytology Lab Samples Received (n) Percentage of Total (%) Hereford Llandough Llandudno Princess of Wales Royal Glamorgan Royal Gwent Singleton Withybush Wrexham Maelor Ysbyty Glan Clwyd Chester West Wales General Prince Charles Princess Royal

17 HPV Sample Processing 1. Arrival 2. Login 3. Storage 4. Tube labelling 5. 4 tubes/ sample 6. Sample prep

18 HPV Sample Processing (n) Samples processed n=12,502 DNA extracted n=12,408 HPV PCR-EIA n=11,186 -Globin PCR Positive n=10,711 96% efficiency Not eligible n=147 Incomplete data n=370 HR HPV only n=2,202 (21.6%) Eligible Study Population 10,194 HR and LR HPV n=602 (5.9%) HPV positive n=3,249 (31.9%) LR HPV only n=445 (4.4%)

19 Cytology in Study Population 82.2% negative (n=8,384) 10.8% borderline (n=1,103) 5.1% mild (n=515) 1.1% moderate (n=108) 0.8% severe (n=83) 0.01% Glandular Neoplasia (n=1)

20 Cytology and HPV

21 SDS in Study Population 20.8% from 10% most deprived LSOAs 20.3% from 10-20% most deprived LSOAs 19.9% from 20-30% most deprived LSOAs 19.5% from 30-50% most deprived LSOAs 19.5% from the 50% least deprived LSOAs

22 SDS and HPV

23 Single and Multiple HPV Infections 44% HR HPV positive cases had a single infection

24 Summary HPV prevalence increased significantly with degree of dyskaryosis HPV 16 and HPV 18 account for the majority of HR HPV infections Baseline data available for comparison with future vaccinated cohorts

25 Proportion of disease attributable to HPV16/18 HPV 16 and 18 are present in around 70% of cervical cancers HPV present in 71.5% of cervical cancers (Europe and North America n=453)

26 HPV in Cervical Cancer in Wales Determine HPV types associated with cervical cancer in Welsh population 453 cervical cancers diagnosed % potentially preventable by vaccination All histological types n % (95% CI) Betaglobin positive 280 HR HPV type identified 273 HPV16 and/or 18 only (73.0 to 82.7) HPV16 and/or 18 present (77.2 to 86.2)

27 Why is our estimate higher? Geographical differences in HPV prevalence Changes in practice of cervical screening Original paper included cases from populations without routine screening Screening may identify and treat slow developing lesions associated with non-vaccine types: Enrich for tumours caused by HPV 16 and 18 Increasing proportion of adenocarcinomas

28 Conclusion The proportion of cervical cancers that could be prevented by the vaccine could be underestimated Vaccination could prevent 78-82% of cervical cancers

29 Time for a change Professor Sasieni said: "The UK cervical screening programme has done a fantastic job in reducing cervical cancer, but it is based on an old screening test. "HPV testing could prevent an even greater proportion of cervical cancer with just half the number of screens over a lifetime in women who have not had the HPV vaccine. Young women who have had the HPV jab would only need two screens giving the "all clear", one at the age of 30 and another at the age of 45, he said. Any with worrying results would be referred for more testing and treatment as necessary.

30 Acknowledgements HPV Research Group Alison Fiander Ned Powell Amanda Tristram Jo Jones Vasiliki Kiparoglou Angharad Edwards Dean Bryant Rachel Raybould Tiffany Onions Sue Ashman Funding Cancer Research Wales Emma Jayne Demery CU Cervical Screening Wales WORD Cervical Screening Wales Hilary Fielder Bryan Rose Anne Hauke Jane McRea Helen Beer/ Kate Gregory Nick Dallimore Shantini Paranjothy Collaborators Cervical Screening Wales UHW Pathology Dept PHW Health Protection Division of Welsh Assembly Government Consultant Malcolm Adams Robert Newcombe

31 Thank you for your attention Any Questions?