Anticipated impact on HPV infection from HPV vaccination programs – cause for optimism

Dr Paddy Horner

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

Koutsky L. Am J Med 1997; 102 (5A): 3–8Koutsky L et al. Epidemiol Rev 1988; 10: 122–63

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

Koutsky L et al. Epidemiol Rev 1988; 10: 122–163

Genital HPV infection

• Associated– Smoking– Multiple sexual partners

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

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 20-60%

Genital warts 200-700 100%

WHO/ICO 2010 UK www. who. int/ hpvcentre & Georgousakis Lancet inf Diseases 2012 DOI:10.1016/S1473-3099(12)70031-2

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

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

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

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%

Women (all)

62% 49%

Kreimer Lancet Oncology 2011;365:1576-85

HPV vaccination

• Men• 4065 boys and men• 90% reduction PIN (inc Warts)• 85% reduction persistent infection

Giuliano NEJM 2011;364:401Palefsky N Engl J Med 2011;365:1576-85.

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%

Giuliano NEJM 2011;364:401Palefsky N Engl J Med 2011;365:1576-85.

•Reduced persistent infection 6/11/16/18 (ITT) 60%•Reduced detection at any time (ITT) 50%

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 - 8.2%

• 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

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: 10.1136/bmj.d6818

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

Proportion of women and men presenting to a STI clinic in Australia between 2004 and 2011

30%

10%

20%

2004 2005 2006 2007 2008 20102009

2011

<21 female<21 maleMen who have sex with men

Vaccination started

Read et al STI 2011;87:544

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:10.1016/S1473-3099(12)70031-2

Cost effectiveness

• Gardasil more cost effective the Cervarix– Significant health care cost genital warts

Jit BMJ 2011;343:5775

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