1. Anticipated impact on HPV infection from HPV vaccination programs – cause for optimism
Dr Paddy Horner

2. Genital human papillomavirus infection
The most common STI worldwide
Spread by skin to skin contact
Sexually active women <25 years old have the highest rate of human papillomavirus (HPV) infection
Majority no visible lesions
Resolve infection after 1-3 yrs – no immunity other types
1% of sexually active adults (aged 15–49 years) develop genital warts
~10% fail to clear infection and at increased complications
Human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases both in the UK and on a global scale.
DNA amplification studies have shown:
>50% of sexually active women aged <25 carry HPV.
By the age of 40 years this has dropped to 5%.
It is estimated that 1% of sexually active adults aged <50 years develop EGW at some time.
Koutsky L. Am J Med 1997; 102 (5A): 3–8 Koutsky L et al. Epidemiol Rev 1988; 10: 122–63

3. Prevalence of genital HPV infection
It is estimated the majority of people will have been exposed to a genital HPV type in their lifetime
Only 1% of a population will have visible at a given time
This diagram graphically illustrates the size of the problem.
Population estimates are for the 15–49 year-old UK population, 2003.
Koutsky L et al. Epidemiol Rev 1988; 10: 122–163

4. Genital HPV infection
Associated
Smoking
Multiple sexual partners

5. HPV subtypes & disease HPV over 100 subtypes
HPV 6, 11 most common -non oncogenic
Genital/anal warts
laryngeal papillomas
HPV 16, 18 – oncogenic
cervical cancer (70%), VIN, VAIN in women
Penile cancer in men
Oral and anal cancer in men and women
HPV 31,33,35,39,45,51,52,56,58,59,68
Jit BMJ 2011;343:5775 & Johnson et al STI 2012;88:212-17

6. Rates of HPV disease Annual incidence (per 100,000)
Proportion attributable to HPV (preventable)
Cervical cancer (2002 UK) 10
99% (70%)
Anal cancer
1-2
(MSM x 33)
85% (60%)
Vulval/Vaginal cancer
3-5
40% (30%)
Penile cancer 1
20-60%
Oral and oropharyngeal
8-10
Genital warts
100%
WHO/ICO 2010 UK www. who. int/ hpvcentre & Georgousakis Lancet inf Diseases 2012 DOI: /S (12)

7. HPV vaccination Vaccines - Gardasil – Merck
Quadrivalent 16, 18, 6, 11 (includes genital warts)
Cervarix – GSK
Bivavlent 16, 18
Prevent HPV infection & pre cancerous lesions
Gardasil more cost effective - warts
Cervarix better cross protection other HPV types
47% vs 23%
Not a treatment for established infection
Administered sexually naive young adolescents
Jit BMJ 2011;343:5775

8. HPV vaccination Duration immunity probably > 10 yrs
Antibody mediated capsular protein
Type specific
Some protection other HPV serotypes
Phylogenetically related
Joura et al BMJ 2012;344:1401

9. HPV vaccination FUTURE I/II – 17,622 women 15-26yrs Risk Group
Disease reduction
CIN1
Warts
HPV 16/18
All types
HPV naive
96%
30%
99%
All
70%
20%
FUTURE I/II BMJ 2010;340:3493

10. Reduction in infection
HPV vaccination
Anal prevalent type 16/18 infection
Women 4210
Risk Group
Reduction in infection
HPV 16/18
HPV 31/33/45
Women
(HPV naive)
83%
61%
(all)
62%
49%
Kreimer Lancet Oncology 2011;365:

11. HPV vaccination Men 4065 boys and men 90% reduction PIN (inc Warts)
85% reduction persistent infection
Giuliano NEJM 2011;364:401
Palefsky N Engl J Med 2011;365:

12. HPV vaccination AIN (inc Warts) 602 Men who have sex with men (MSM)
Risk Group
Disease reduction
AIN
HPV 6/11/16/18
HPV 16/18
All types
MSM ( HPV –ve)
77%
79%
55%
MSM (all)
50%
25%
Reduced persistent infection 6/11/16/18 (ITT) 60%
Reduced detection at any time (ITT) 50%
Giuliano NEJM 2011;364:401
Palefsky N Engl J Med 2011;365:

13. HPV vaccination Not a treatment for current infection/disease
FUTURE I/II studies:
Women with treated cervical disease increased risk of future CIN 1 or worse %
New infection
Risk reduced by 48% if received vaccine (quad) - 4.3%
Evidence that vaccine beneficial even in those with disease
Joura BMJ 2012;344:1401

14. HPV vaccination Could it alter natural history of CIN/VIN/AIN?
Efficacy phase II/III treatment anogenital warts
Is vaccine immunogen expressed in CIN/VIN/AIN?
Effect of Vaccine on CIN progression to cancer unknown
Data does not support vaccine efficacy
Natural history AIN probably differs CIN
Longer duration before malignant transformation
Greater similarity to VIN
Vaccine reduces persistent infection
Could it alter the natural history of AIN?
Simpson BMJ 2011;343:d6818 doi: /bmj.d6818

15. Genital warts Australia Using vaccine in young women since 2007
>70% uptake adolescents
Reviewed clinic data Melbourne GUM clinic
Women < 21
Men < 21
MSM
Marked reduction in both female and male warts
Not in MSM
Read et al STI 2011;87:544

16. Proportion of women and men presenting to a STI clinic in Australia between 2004 and 2011
Vaccination started
30%
10%
20%
2004
2005
2006
2007
2008
2010
2009
2011
<21 female
<21 male
Men who have sex with men
Read et al STI 2011;87:544

17. HPV vaccination and Men
Heterosexual herd immunity effective for men
>70% coverage women
Not all countries have attained this
Vaccination boys recommended USA but not UK
MSM remain at risk
Unable to identify as an adolescent
Many >20 partners by age 20
Highly HPV exposed
AIN much longer time course to Cancer
HIV co-factor
Pros and cons discussed Georgousakis Lancet inf Diseases 2012 DOI: /S (12)

18. Cost effectiveness Gardasil more cost effective the Cervarix
Significant health care cost genital warts
Jit BMJ 2011;343:5775

19. But! Population based survey UK 18-44 yrs
16% women had high risk HPV type
Only 1/3rd were type 16/18
Suggests HPV 16 probably more oncogenic
Condoms had some protective effect!
Johnson et al STI 2012;88:212-17