3.the cost effectiveness & real world impact of quadrivalentPresentation Transcript
The Cost Effectiveness & Real World Impact ofQuadrivalent HPV vaccine Endy M. Moegni KOGI XV Bali Nusa Dua Convention Center 29 Juni- 5 Juli 2012
Quadrivalent HPV Vaccine (4 in 1 HPV vaccine) Diphtheria antitoxin discovered Measles (live)* Human Papillomavirus* Mumps* Zoster (live)* Measles (live attenuated virus)* Rotavirus* Measles, mumps, rubella (MMR)* Pneumococcal (14-valent polysaccharide)*1895 1963 1967 1968 1971 1977 1978 1981 1983 1986 1989 1995 1996 1996 1996 2005 2006 2006 2006 Measles, mumps, rubella, varicella* The First Cancer Vaccine Haemophilus influenzae type b / Hepatitis B* Haemophilus influenzae type b (liquid)* of the World Hepatitis A (inactivated)* Varicella (chicken pox) virus* Haemophilus influenzae type b (conjugated)* Hepatitis B (recombinant)* Pneumococcal (23-valent polysaccharide)* Hepatitis B (plasma derived)* Measles, mumps, rubella virus vaccine live (new rubella strain: RA 27/3)* Tam Kar Fai
Cervical Cancer Is Essentially Caused by Oncogenic HPV HPV is a main cause of cervical cancer Analysis of 932 specimens from women in 22 countries indicated prevalence of HPV DNA in cervical cancers worldwide = 99.7%.1. Muñoz N, Bosch FX, de Sanjosé, et al. N Engl J Med. 2003;348:518–527. 2. Walboomers JM, Jacobs MV, ManosMM, et al. J Pathol. 1999;189:12–19.
HPV and Anogenital Warts HPV 6 and 11 responsible for >90% of anogenital warts1 Clinically apparent in ~1% of sexually active US adult population2 Estimated lifetime risk of developing genital warts ~10%3,4Images top left and top right: Reprinted with permission fromNZ DermNet (www.dermnetnz.org)1. Jansen KU, Shaw AR. Annu Rev Med. 2004;55:319–331. 2. Koutsky L. Am J Med. 1997;102:3–8. 3. Franco EL,Villa LL, Richardson H, Rohan TE, Ferenczy A. In: Franco EL, Monsonego J, eds. Oxford, UK: Blackwell Science;1997:14–22. 4. Tortolero-Luna G. Hematol Oncol Clin North Am. 1999;13:245–257, x.
Vaginal Intraepithelial Neoplasia (VaIN) Main predisposing factor for VaIN is likely exposure to HPV.1 – VaIN is often found in conjunction with cervical intraepithelial neoplasia (CIN). 1. Winter-Roach B, Monaghan JM, de Lopes A. Colposcopy of the vagina. In: Bosze P, Luesley D, eds. EAGC Course Book on Colposcopy.
Vulval Intraepithelial Neoplasia (VIN) HPV 16 appears to be the dominant HPV type associated with high-grade VIN (up to 81% in VIN 3)3 – Majority of VIN 1 cases are associated with HPV types 6 and 11 3 – HPV 6, 11, 16, or 18 can be found in VIN 2 or 3 4 Photo courtesy of Dr. J. Monsonego Photos courtesy of Dr. E.J. Mayeaux. 3. Buscema J, Naghashfar Z, Sawada E, et al. Obstet Gynecol. 1988;71:601–606. 4. Koutsky L. Am J Med.1997;102:3–8..
VaIN and VIN are of concern because they are considered as precancerous lesions with about 40 - 50% associated with HPV infection In UK, vulval cancer is 6 times and vaginal cancer 20 times less common than cervical cancer1 No screening programme exists1. Gonzalez Inchaurraga MA et al. HPV and carcinogenesis. Acta Dermatovenerol. 2002;1:1-8.2. Parkins DM et al. International Agency for Research on Cancer, 2002;8.
Phylogenetic Tree of HPV Family HPV 16 RelatedHPV18Related
Infection From Time of First 12 16 20 24 28 32 36 40 44 48 52 56 Sexual Intercourse Study of female college students (N=603) Months Since First Intercourse 8 4 0 1.0 0.8 0.6 0.4 0.2 0.0From Winer RL, Lee S-K, Hughes JP, Adam DE, Kiviat NB, Koutsky LA. Genital human papillomavirus infection:Incidence and risk factors in a cohort of female university students. Am J Epidemiol. 2003;157:218–226, by HPV Infectionpermission of Oxford University Press. Cumulative Incidence of
Treatment of HPV Infection
Quadrivalent HPV L1 VLP Vaccine1 Quadrivalent HPV L1 VLP vaccine – (Types 6, 11, 16, 18) VLPs manufactured in: – Yeast – Recombinant VLPs (empty shell protein L1) – Do not contain Virus DNA (not infectious) Amorphous Aluminum Hydroxyphosphate Sulfate Adjuvant (225 μg per dose) No Mercury preservative (thimerosal) Storage: 2 to 8 OCGARDASIL is a trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.*VLP = Virus-like particle. 1. Villa LL, Costa RL, Petta CA, et al. Lancet Oncol. 2005;6:271–278.
Dosage & Administration3 doses within 6 months – (0, 2, 6 months) 0.5mL volume IM injection Package: – Prefilled syringe – Shake well before use Injection Site: – Upper arm (Deltoid region) – Thigh (higher anterolateral area)
Gardasil / Silgard ApprovalsGARDASIL approved in 127 countries (includes 24 GAVI-eligible) Europe:Caribbean & Central America: North America: Germany Cyprus Ireland France Czech Republic LatviaCosta Rica Trinidad/Tobago USA UK Denmark LithuaniaPuerto Rico El Salvador Canada Spain Estonia LuxembourgGuatemala Honduras Italy Finland Malta Asia Pacific & Japan: MexicoCuraçao Nicaragua Austria Greece Netherlands KyrgyzstanBermuda Panama Belgium Hungary Norway UzbekistanBahamas Cayman Islands Bulgaria Iceland Poland KazakhstanBarbados Aruba Portugal Romania Slovakia AustraliaJamaica Dominican Republic Slovenia Sweden Serbia Indonesia Korea 42 Montenegro Bosnia Switzerland Russia Liechtenstein Belarus Taiwan Croatia Turkey Ukraine Hong KongSouth America:Brazil Bolivia 3 Herzogovina Macedonia Albania Singapore New ZealandArgentina Uruguay MacauPeruColombia Ecuador Chile 16 35 22 Malaysia Philippines ThailandParaguay 9 India VietnamMiddle East & Africa: Fiji BhutanGabon NamibiaIsrael C.A.R. GeorgiaMorocco Mauritius JAPANKenya Kuwait Sri LankaMauritania UAE BruneiGuinea Eq. EthiopiaUganda TogoMalawi Congo Brazzaville GAVI – Eligible Registration Approvals (24): Burkina Faso, Cameroon, CentralJordan Egypt African Republic, Chad, Congo (DR), Cote d’Ivoire, Ethiopia, Guinea (Conakry),Cote d’Ivoire Burkina Faso India, Kenya, Kyrgyzstan, Malawi, Mali, Mauritania, Nicaragua, Nigeria, Pakistan,Chad Bahrain Botswana Rwanda, Tanzania, Togo, Uganda, Uzbekistan, Vietnam, ZambiaLebanon Tanzania ZambiaSouth Africa Cameroon NigeriaPakistan Tunisia MaliGuinea Conakry Saudi Arabia Rwanda as of 8 June 2012
HPV Recommendations by National Expert Advisory Bodies on Immunization: 40 Countries National Funding by 38 Countries 23 Europe Austria3 Belgium Bulgaria North America Czech Republic Denmark USA France Canada Germany Mexico Greece Iceland Ireland Italy Latvia Luxemburg Macedonia Netherlands2 Norway Portugal Caribbean & Central America Romania Slovenia Puerto Rico Spain Panama Sweden Switzerland United Kingdom3 Cayman Is.South AmericaArgentinaPeruGuyana FUNDING 6 Asia Pacific GARDASIL only Australia Bivalent Only 3 New Zealand Malaysia Both vaccines Middle East & Africa India No funding Singapore Kuwait Japan UAEUpdate: June 8, 2012 Lesotho
HPV Vaccine: National Immunization Program 15 countriesEleven European countries (Germany, France, Italy, Belgium, Austria, Norway, Sweden, Greece, Denmark, Luxemburgand Switzerland), as well as the United States, Canada, Australia and UK have already reviewed the positive public health impact and recommended the quadrivalent HPV vaccine for universal human papillomavirus vaccinationwith accelerated reviews.
Sustained clinical efficacy and antibody titer for at least 5 years GMT (mMU/mL) GARDASIL 100% 10 000Neutralising antibodies GARDASIL Clinical efficacy* 1 000 (HPV type 16) 100 10 Natural infection 0 7 12 18 24 30 36 54 60 months 5 years 1st 2nd 3rd Dose * against infection, CIN (Cervical intraepithelial neoplasia) and genital warts due to HPV types 6,11,18; 5 yrs follow up (after dose 1) of a subset (241 women, Villa L High Sust Eff Proph Quad HPV Vacc 5 Year Followup Br J vaccine Can 2006 95 1459 & placebo) from a phase II efficacy study
Long Term Response Modified power law model Conventional power law modelThe conventional power law model estimated a median duration of detectableantibody of 32 years.The modified power law model predicted a long-term plateau of antibodyduration with a near life-long persistence above the level of detection.Model-based prediction of GMTs and proportions above different thresholds following HPV-16 L1 VLP vaccination predicted from the models.GMTs predicted from the power-law(- - -) and modified power law(—) models, using antibody data measured during 48 months followingHPV-16L1 VLP vaccination are shown for 30 yrs. 1. C. Fraser et al. / Vaccine 25 (2007) 4324–4333
CDC 2010 Mar – Gardasil Q&A for publicAccessed 10 Jul 2010http://www.cdc.gov/vaccines/pubs/vis/downloads/vis-hpv-gardasil.pdf
Australia Free NationalHPV vaccination Program Malaysia Free NationalHPV vaccination Program
The near disappearance of genital warts in young women 4 years after commencing a national human papillomavirus (HPV) vaccination programmeTim R H Read,1 Jane S Hocking,2 Marcus Y Chen,1 Basil Donovan,3Catriona S Bradshaw,4 Christopher K Fairley1
• From July 2004 to June 2011, • 52 454 new patients were seen at Melbourne Sexual Health Centre and 5021 (9.6%, 95% CI 9.3% to 9.8%) were diagnosed with GW. • From July 2004 to June 2007, the proportions with GW either increased or did not change in all groups.Tim R H Read,1 Jane S Hocking,2 Marcus Y Chen,1 Basil Donovan,3Catriona S Bradshaw,4 Christopher K Fairley1
• The two 12-month periods of 2007/2008 and 2010/2011, GW declined in women under 21 years from 18.6% to 1.9% and in heterosexual men under 21 years from 22.9% to 2.9%. • There was no significant change in GW in women $30 years (OR 0.97, 95% CI 0.84 to 1.12), heterosexual men $30 years (OR 0.97, 95% CI 0.89 to 1.06) or in homosexual men (OR 0.95, 95% CI 0.85 to 1.07).Tim R H Read,1 Jane S Hocking,2 Marcus Y Chen,1 Basil Donovan,3Catriona S Bradshaw,4 Christopher K Fairley1
Conclusions• The dramatic decline and near disappearance of GW in women and men under 21 years of age, 4 years after commencing this programme, suggest that the basic reproductive rate has fallen below one.
Comparative Cost-Effectiveness of HPV Vaccines in the Prevention of Cervical Cancer in Malaysia • Cost effectivenes options were compared for three programs i.e. screening via Pap smear; modeling of HPV vaccination (QV and BV) and combined strategy (screening plus vaccination).Sharifa WP Ezat1*, Syed Aljunid2
Methods Forthis cross sectional study in 2006-2009 respondents were interviewed from six public Gynecology-Oncology hospitals. (502 cervical cancer patients participated). Methods included expert panel discussions to estimate treatment costs by severity and direct interviews with respondents using costing and quality of life questionnaires. Sharifa WP Ezat 1*, Syed Aljunid2
Results A total of 502 cervical cancer patients participated with a mean age at 53.3±11.2 years and a mean marriage length of 27.7±12.1 years, Malays accounting for 44.2%. Cost/quality adjusted life year (QALY) for Pap smear Cost/quality adjusted life year (QALY) for strategy with HPV vaccination only Cost/quality adjusted life year (QALY) for strategy with combined strategy (screening + HPV vaccination)
Results(Incremental Cost Effectiveness Ratio (ICER))
Conclusions QV is more cost effective than BV. The QV combined strategy was more cost effective than any method except Pap smear screening with high population coverage. Sharifa WP Ezat 1*, Syed Aljunid2
Comparing Bivalent and Quadrivalent Human Papillomavirus Vaccines: Economic Evaluation Based on Transmission Model Author: Jit et al
Results Effect on disease: – Use of either vaccine is expected to substantially decrease the incidence of HPV related cancers regardless of which scenario is assumed – By 2109, HPV vaccine may prevent: Cervical cancer cases vulval, vaginal, reduction and anal cancers cases reduction QHPV 700 (630–800) to 430 (380–490) to 1000 (940–1100) 630 (950–670) BHPV 730 (650–830) to 1100 (990–1200) – Use of the qHPV is expected to decrease the incidence of vaccine type warts and recurrent respiratory papillomatoses by up to 95% if duration of protection is lifelong.Jit et al. 2011. BMJ 2011;343:d5775
Conclusions• The quadrivalent vaccine may have an advantage over the bivalent vaccine in reducing healthcare costs and QALYs lost .
UK switched to QV from Sept 2012 United Kingdom (UK) Department of Health announced that from next September 2012, UK will use QV for HPV vaccination program in UK QV protects against the two types of HPV virus that cause more than 70 percent of cervical cancer in England and two types of HPV virus that cause 90 percent of genital warts.
Eradication of Cervical Cancer and HPV Related Diseases Not a Dream Anymore…
References• Donovan et al. 2010. Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillance data. DOI:10.1016/S1473- 3099(10)70225-5• Read et al. The near disappearance of genital warts in young women 4 years after commencing a national human papillomavirus (HPV) vaccination programme. Sex Transm Infect. doi:10.1136/sextrans-2011-050234• Ezat et al. 2011. Comparative Cost-Effectiveness of HPV Vaccines in the Prevention of Cervical Cancer in Malaysia. Asian Pacific J Cancer Prev, 11, 1-6.• Jit et al, Comparing bivalent and quadrivalent human papillomavirus vaccines: economic evaluation based on