HPV in Richard Gilson

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HPV in 2016 Richard Gilson Reader in Sexual Health and HIV Centre Sexual Health and HIV Research UCL Research Department of Infection and Population Health RCP-BASHH September 2016

HPV in 2016 Prevention of HPV infection Vaccination programme in girls Pilot programme in MSM Treatment of genital HPV disease Current options for treatment

Plantar Warts Cutaneous (mostly asymptomatic) Genital mucosa (cancer associated) Common and flat warts External genital warts 7 De Villiers 2004 HPV Vaccination pilot for MSM

HPV cause of genital and extra-genital cancer Cervical Vulvo-vaginal Anal Penile Any HPV HPV 16/18 Oropharyngeal 0 20 40 60 80 100 Percentage After Jit et al 2011

HPV vaccine - implementation in the UK National HPV vaccine programme primary aim reduce cervical cancer incidence and mortality started in September 2008 bivalent vaccine HPV16/18 girls aged 12-13 catch-up programme in young women up to 18 years boys not included not cost-effective

HPV vaccine - implementation in the UK National HPV vaccine programme started in September 2008 bivalent vaccine HPV16/18 girls aged 12-13 catch-up programme in young women up to 18 years Switch to quadrivalent vaccine from September 2012 - HPV 6/11 and HPV 16/18 also protects against genital warts 3 doses 0, 2, 6-12 months

Proportion of cervical cancer attributable to typespecific HPV infection HPV 16 and 18 cause 70% of cervical cancers 90% of cervical cancer associated with 9 HR HPV types Clifford G, et al. Vaccine 2006. Muñoz N, et al. Int J Cancer, 2004.

Next generation vaccine: Gardasil9 Same protection against HPV6/11/16/18 after adjustment of the antigen dose Increases the proportion of cancers prevented Extended protection against high-risk types: HPV 31, 33, 45, 52, 58 No additional benefit against genital warts Schedule: 3 doses Licensed but not yet used in the UK

HPV vaccine coverage, year 8 females PHE data 9

HPV16/18 prevalence (%) Prevalence of HPV16/18 among 16-18 year old females 20 18 16 14 12 10 8 6 4 2 0 pre-immunisation (2008) post-immunisation (2010-2011) post-immunisation (2012-2013) Prevalence estimate from HPV DNA testing of chlamydia screening samples NCSP/PHE 10

HPV vaccine - implementation in the UK National HPV vaccine programme started in September 2008 bivalent vaccine HPV16/18 girls aged 12-13 catch-up programme in young women up to 18 years Switch to quadrivalent vaccine from September 2012 - HPV 6/11 and HPV 16/18 also protects against genital warts 3 doses 0, 2, 6-12 months Reduction to 2 doses for girls under 15 years of age only (from 2014) 0, 6-12 months

HPV vaccine - implementation in the UK National HPV vaccine programme started in September 2008 bivalent vaccine HPV16/18 girls aged 12-13 catch-up programme in young women up to 18 years Switch to quadrivalent vaccine from September 2012 - HPV 6/11 and HPV 16/18 Reduction to 2 doses for girls under 15 years of age only Targeted programme for men who have sex with men pilot implementation

Percent of clinic attendees Proportion of Australian-born women with genital warts by age group, 2004-2011 20 18 16 14 12 10 8 6 4 2 0 <21 years 21-30 years >30 years 2004 2005 2006 2007 2008 2009 2010 2011 Ali H etal; Genital warts in young Australians five years into national human papillomavirus vaccination programme: national surveillance data. BMJ 2013;346:

Percent of clinic attendees Proportion of Australian-born heterosexual men with genital warts by age group, 2004-2011 (Ali H et al BMJ 2013) 20 18 16 14 12 10 8 6 4 2 0 <21 years 21-30 years >30 years 2004 2005 2006 2007 2008 2009 2010 2011

Percent of clinic attendees Proportion of Australian-born MSM with anogenital warts, 2004-2011 20 18 16 14 12 10 8 6 4 2 0 9.0% 8.5% 6.4% 2004 2005 2006 2007 2008 2009 2010 2011

HPV prevalence in MSM attending a sexual health clinic potential for prevention? (King et al 2014) No HPV 67.5% 1 type 25.1% 2 types 6.7% 3 types 0.8% 4 types 0%

Rationale for targeted vaccination of MSM MSM who attend GUM, sexual health and HIV treatment services high incidence of HPV infection but many are still susceptible include more men with high risk sexual behaviour and other STIs HPV 16-associated anal cancer is more common in MSM compared to heterosexual men incidence of anal cancer is also highest in HIV positive MSM; MSM would benefit from direct effect of vaccine. 17

HPV vaccination in MSM Joint Committee on Vaccination and Immunisation (JCVI) recommendation 2015 Targeted vaccination of MSM attending sexual health/hiv services. Age up to 45 Quadrivalent vaccine bivalent not cost effective Provided that: Vaccine procurement and delivery process can be agreed Vaccine cost should be at national procurement rate Delivery cost is low

HPV vaccination in MSM pilot Selected centres in England agreed to date Brighton Bournemouth/Weymouth Milton Keynes Norwich/Great Yarmouth London Central Middlesex/Northwick Park Chelsea and Westminster/Dean Street/Hammersmith Broadway St Mary s Mortimer Market

HPV vaccine - implementation in the UK National HPV vaccine programme started in September 2008 bivalent vaccine HPV16/18 girls aged 12-13 catch-up programme in young women up to 18 years Switch to quadrivalent vaccine from September 2012 - HPV 6/11 and HPV 16/18 Reduction to 2 doses for girls under 15 years of age only Targeted programme for men who have sex with men pilot implementation started August 2016 Gender neutral vaccination vaccination of all boys in parallel with girls, age 12/13 still under consideration economic analysis on-going

HPV treatment of genital warts BASHH guidelines 2015 included flow charts first line therapy topical podophyllotoxin vs imiquimod New therapy one new therapy Cataphen

BASHH HPV Guidelines 2015

BASHH HPV Guidelines 2015

HPV treatment of genital warts Catephen European licence in 2015 (MAH: Kora; manufacturer: Medigene) Extract of Camelia sinensis green tea plant Contains epigallocatechingallate Also available as Veregen in other countries (also Polyphenon E) Topical ointment 3 times a day for up to 16 weeks Response similar to other agents clearance in 53.6% vs 35.4% with placebo Local reactions common Cost high compared to podophyllotoxin preparations Possible alternative no comparative data

HPV in 2016 Prevention of HPV infection Vaccination programme in girls very successful with high coverage rates Pilot programme in MSM just starting, to demonstrate that it can be delivered in a cost-effective way Treatment of genital HPV disease Current options for treatment no major developments, question remains as to what is the best treatment to start with. Role of vaccine unproven. Immunotherapeutic candidate vaccines show limited efficacy.