Dr. Unjali Malhotra Women s Health updates CCFP Women s Health FCFP NCMP Program Director UBC Women s Health Chair Canadian Foundation for Women s Health
HPV
The ANTI CANCER Vaccines QUADrivalent HPV Vaccine Cervical Cancer Genital Warts Anal Cancer Vaginal, vulvar Cancer Men aged 9 26 Women aged 9 45 School Program NONAvalent HPV Vaccine Cervical Cancer Genital warts Anal Cancer Vulvar Cancer Vaginal Cancer Women 9 45 Men 9 26
Parent Barrier: Knowledge As the vaccine is targeted at pre teens and teens, it is important for parents to accept vaccination 1. Mays et al. Soc Sci Med. 2004;58:1405 13; 2. Davis et al. J Lower Gen Tract Dis 2004; 8:188 94 4
Limitations of Cytologic Screening False negative Acceptability or access issues 20 25% Performance issues 2/3 sampling No previous screening or too long ago 50 60% 8 15% 1/3 detection Inadequate follow up Cytologic screening is not sufficient for prevention of cervical cancer, considering the high, bimodal incidence of HPV infection. Also, it does not prevent genital warts or non cervical cancer Treatment failure Rapid evolution of cancer 1. Spence et al. Preventive Medicine. 2007;45:93 106. 5
When counseling.. PREVENTION vs. screening
Safety Consensus Among Global Health Authorities (FDA, CDC, WHO, EMA, ECDC) To date, no safety concerns for the use of qhpv vaccine have arisen from ongoing surveillance studies in females and males 1 6 Postlicensure adverse events in males were similar to those observed in females and/or those found in males in prelicensure clinical trials 1 Recommend continued monitoring for the safety of qhpv vaccine in both genders 1 6 CDC=Centers for Disease Control and Prevention; ECDC=European Centre for Disease Prevention and Control; EMA=European Medicines Agency; FDA=Food and Drug Administration; qhpv=quadrivalent human papillomavirus; WHO=World Health Organization. 1. Harrington T. Presented at: National Foundation of Infectious Diseases 15th Annual Conference on Vaccine Research; 7 9 May, 2012; Baltimore, MD. Presentation 3B. 2. Gee J. Presented at: Advisory Committee on Immunization Practices Meeting; October 25, 2011; Atlanta, GA. 3. Food and Drug Administration (FDA). http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/pediatricadvisorycommittee/ucm302352.pdf?utm_campaign=google2&utm_source =fdasearch&utm_medium=website&utm_term=pediatric Advisory Committee UCM302352&utm_content=1. Accessed May 29, 2012. 4. World Health Organization (WHO). Wkly Epidemiol Rec. 2009;84:37 40. 5. European Medicines Agency (EMA). http://www.ema.- europa.eu/docs/en_gb/document_library/epar_procedural_steps_taken_and_scientific_information_after_- authorisation/human/000703/wc500021147.pdf. Accessed March 21, 2012. 6. ECDC Guidance 2012. http://www.ecdc.europa.eu/en/publications/publications/20120905_gui_hpv_vaccine_update.pdf. Accessed 24 September 2012.
Safety and Tolerability of 9v HPV Vaccine in Boys/Girls Age 9 15 and Women Age 16 26 9v HPV vaccine displayed an adverse event profile generally comparable to that of 4v HPV quadrivalent; 9v: nine valent. 1. Joura et al. N Engl J Med. 2015;372:711 23.
It works! Efficacy of a novel 9 valent HPV vaccine in 16 26 year old women Per protocol population Endpoint High grade HPV31/33/45/52/58 cervical/vulvar/vaginal disease Any grade HPV31/33/45/52/58 cervical/vulvar/vaginal disease HPV31/33/45/52/58 6 months related persistent infection Joura E at al: N Engl J Med 2015;372:711 23 9vHPV vaccine No cases/n qhpv Vaccine No of cases/n 1/6016 30/6017 3/6016 103/6017 35/5939 810/5953 Efficacy (95%CI) 96.7 % (80.9 99.8) 97.1 % (91.8 99.2) 96.0 % (94.4 97.2)
Is vaccination after LEEP preventing recurrences in patients with CIN 2 3?Results 8 6 NO vaccination after LEEP was an independent risk factor for recurrent CIN2 3 HR = 2.840 (p<0.01) Recurrence Rate % 4 2 2.5% Vaccine 7.2% No vaccine 0 Kang W. D., et al. Gynecologic Oncology 2013, 130:264 268.
SPERANZA STUDY: PRELIMINARY RESULTS OF HPV VACCINATION AFTER LEEP Recurrence Rate % 10 8 6 4 2 0 Vaccination after treatment may prevent new infections or reinfection with the same HPV subtype. 1.2% Vaccine 6.8% No vaccine Gherlardi et al. Presented at Eurogin, Feb 2015, June 2016
HPV Infection Has a Bimodal 70 Distribution HPV prevalence (%) 60 50 40 30 20 10 ** ** ** * Total Single HR Single LR Multiple ** ** ** 0 10 20 21~30 31~40 41~50 51~60 >60 n=370 n=4939 n=5432 n=3902 n=472 n=152 Age Group (years) *p<0.005; **p<0.01. HPV: human papillomavirus; HR: high risk; LR: low risk. 1. Liu et al. BMC Infect Dis. 2014 19;14:708. 12
Women Remain at Risk for Acquiring HPV Infection Throughout Their Lifetime 50 Cohort of Colombian Women (n = 1,610) Cumulative Risk of HPV Infection (%) 40 30 20 10 Age at Baseline (years) 15 19 20 24 25 29 30 44 45+ 0 0 1 2 3 4 5 Years Muñoz N, et al. J Infect Dis 2004; 190:2077-87.
How many doses \ do I need? NACI Guidelines: Gardasil 9 : there is insufficient evidence to recommend a 2 dose schedule in any population Ideally the length of time between the first and last dose should be 24 weeks (6mo) Females: Ages 9 14 can do 2 or 3 doses of HPV 2 or HPV 4 (3 doses HPV) Males 9 14 can do 2 or 3 doses of HPV 4 (3 doses of HPV9) Females > 15 y : 3 doses HPV 2, 4, 9 Males > 15 y : 3 doses HPV 4, 9 Immunocompromised, HPV + : 3 doses HPV 2, 4, 9
NACI Update on HPV9 April 2016 2 dose HPV9? Insufficient evidence to recommend 2 dose schedule for HPV9 vaccine (studies ongoing). However, there is a theoretical basis for individuals <age 15 (immunocompetent, non HIV infected) to consider 2 doses of HPV9 vaccine. This expert opinion (unpublished evidence) is based on previous studies of HPV2 & HPV4 vaccines among adolescents. National Advisory Committee on Immunization 2016 15
What if I have been immunized with another HPV vaccine? NACI Guidelines: If you have already had gardasil 4, whilst it is safe to re immunize, it is not the current recommendation
Will I need a booster in the future? NACI: We can t promise you won t need a booster down the road but at this time it does not look like you will
Summary HPV Vaccination Standard of Care HPV Vaccines are safe and effective Adult women remain at risk to HPV infection thorough their sexual life NACI recommends HPV vaccination NACI has no upper age limit for women Recommended for those with previous pap abnormalities, cervical cancer, and AGW Demonstrated efficacy in prevention of recurrence of CIN2/3 A patient is over 35 times more likely to receive 1 dose of HPV vaccine if physician strongly recommends the vaccine Gerent M.A., et al. Sex Transm Infect 2015; 0:1-4.