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Human Papillomavirus Infection in Wales How Big is the Problem Prior to Vaccination?

Human Papillomavirus Infection in Wales How Big is the Problem Prior to Vaccination?. Dr Sam Hibbitts HPV Research Team Obstetrics & Gynaecology School of Medicine Cardiff University. Human Papillomavirus Infection . Essential underlying cause of cervical cancer

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Human Papillomavirus Infection in Wales How Big is the Problem Prior to Vaccination?

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  1. Human Papillomavirus Infection in Wales How Big is the Problem Prior to Vaccination? Dr Sam Hibbitts HPV Research Team Obstetrics & Gynaecology School of Medicine Cardiff University

  2. Human Papillomavirus Infection • Essential underlying cause of cervical cancer • up to 99.7% of invasive cervical carcinomas • HPV infection is common although most are transient and do not result in cancer • Women have an 80% lifetime risk of infection • 80% HPV infections are cleared within 1 year • High Risk (HR) HPV types linked with anogenital neoplasia development • Low Risk (LR) HPV associated with genital warts and laryngeal papillomas

  3. Major Steps in Cervical Cancer Development

  4. Human Papillomavirus Prevalence • Worldwide HPV prevalence in women with normal cytology ca 10.4% • Geographical: highest levels detected in Africa (22.1%) and lowest in Asia (8.0%) • Age: highest levels on women aged 35 or less • The 5 most common HR HPV types are 16, 18, 31, 58 and 52 • HR HPV types 16 and 18 account for more than 70% of cervical cancers de Sanjosé S, Diaz M, Castellsagué X, Clifford G, Bruni L, Muñoz N, Bosch FX. (2007). Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta analysis. Lancet Infect Dis. 7(7): 453-459.

  5. Meta-analysis of HPV Prevalence de Sanjosé S, Diaz M, Castellsagué X, Clifford G, Bruni L, Muñoz N, Bosch FX. (2007). Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta analysis. Lancet Infect Dis. 7(7): 453-459.

  6. Prophylactic HPV Vaccination • Simple structure, based on L1 capsid protein • Virus Like Particles (VLP) • Spontaneous assembly

  7. September 2008 Primary delivery pre-exposure to the virus i.e. before sexual debut (12-14 yrs) Autumn 2009 “catch-up” campaign (16-18 yrs) Autumn 2010 “catch-up” campaign (15-17 yrs) “Catch-up” programme aims to have vaccinated women entering routine screening from 2011. HPV Vaccination Schedule

  8. Before Prophylactic HPV Vaccination….. • Require baseline data to quantify the effects of vaccination • Type replacement • Cross Protection • Fraction of disease prevented

  9. Objectives • To characterise HPV prevalence in South Wales prior to implementation of prophylactic HPV vaccination. • To predict the effects of this program on the population.

  10. South Wales Study Population • Consecutive, anonymous, Liquid Based Cytology (LBC) samples collected in a 5mth time period in 2004 in collaboration with Cervical Screening Wales • Study population : • 10,000 women attending for routine screening in South Wales • Anonymised samples with information available : • Cytology result • Age • Social Deprivation Score (SDS)

  11. HPV Typing Method • PCR-ELISA was performed on all specimens in a 96-well format. • Two tier method was applied: • An initial PCR-ELISA with a cocktail of HR or LR type-specific probes • Sub-typing of all ‘HR’ positive samples with the following individual 14 ‘HR’ HPV probes: HPV 16; 18; 31; 33; 35; 39; 45; 51; 52; 56; 58; 59; 66 and 68. • Re-analysis of 10% of all samples processed was undertaken for internal quality assessment purposes. Jacobs MV, Snijders PJ, van den Brule AJ, Helmerhorst TJ, Meijer CJ, Walboomers JM. A general primer GP5+/GP6(+)-mediated PCR enzyme immunoassay method for rapid detection of 14 high-risk and 6 low-risk human papillomavirus genotypes in cervical scrapings. J Clin Microbiol 1997; 35: 791-795.

  12. Overall HPV prevalence 13.5% Age-standardised HPV prevalence 9.3% HR HPV type distribution in South Wales

  13. Single Infections Multiple Infections 40 35 30 25 Infections (%) Distribution of Single and Multiple 20 15 10 5 0 16 18 31 33 35 39 45 51 52 56 58 59 66 68 HR HPV Type Single and multiple infections: The distribution of HR HPV types • 42% of all HPV infections were with a single HR type

  14. HPV Prevalence: Distribution with Age • 66% of all HR HPV and 58% of all LR HPV infections were in women aged 30 years or less

  15. HPV Prevalence: Distribution with Cytology • Significant increase in the proportion of HR HPV positives from 7% in cytology negative up to 80% in samples with severe cytological abnormalities.

  16. Distribution of HR HPV Infections in each cytology grade: The proportion of HPV 16, HPV 18 and Non HPV 16/18 infections • 27% of all HR HPV infections were HPV 16/18 positive • 26% of HR HPV infections in cases with negative cytology • 47% of HR HPV infections in cases with severe dyskaryosis

  17. Interpretation • The baseline HPV prevalence in South Wales is 13.5% • One quarter of all HR HPV infections could be prevented by current vaccines • In cases of severe cytological abnormality half were linked with non-vaccine HR types and would not be prevented by current vaccines • Continued surveillance of HR HPV types 31, 33, 39 and 58 is recommended following HPV vaccination in Wales

  18. Acknowledgement HPV Research Group Jo Jones Ned Powell Amanda Tristram Alison Fiander Collaborators Cervical Screening Wales (Hilary Fielder, Anne Hauke) Cytology Service Llandough (Nick Dallimore, Jane McRea) Funding Cervical Screening Wales WORD Emma Jane Demery

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