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 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

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

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 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

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;365:1576-85

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;365:1576-85.

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% 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;365:1576-85.

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 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

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