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):

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):

6. Prophylactic HPV Vaccination
Quadrivalent Vaccine
(Sanofi-Pasteur MSD)
Bivalent Vaccine
(GSK)
Reference
Villa LL et al., Lancet Oncology 2005, 6:
Harper DM et al., Lancet :
Efficacy in preventing:
Persistent HPV type infections
89%
(95% CI: 70-97
P/V: 47/6 events)
100%
(95% CI:
P: 16 events)
Type specific lesions
(95% CI: )
10 placebo events
(95% CI: )
6 placebo events
Simple structure, based on L1 capsid protein
Virus Like Particles (VLP)
Spontaneous assembly

7. HPV Vaccination Schedule
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.

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:

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

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

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