HPV Vaccine: HPV Vaccine:

Cervical Cancer VaccineCervical Cancer Vaccine

Dr. Nelly Mugo Dr. Nelly Mugo

Department of Obstetrics & GynaecologyDepartment of Obstetrics & Gynaecology

KNH-SRC Vaccine KNH-SRC Vaccine Symposium, 3Symposium, 3rdrd June 2011 June 2011

OutlineOutline

• Epidemiology of HPV Epidemiology of HPV

• Cervical Cancer- Size of the problemCervical Cancer- Size of the problem

• HPV Vaccine Research FindingsHPV Vaccine Research Findings– Study PopulationStudy Population– EfficacyEfficacy– Cross ProtectionCross Protection– Adverse effectAdverse effect

• Schedule of VaccineSchedule of Vaccine

• Unanswered questions regarding HPV VaccineUnanswered questions regarding HPV Vaccine– Challenges in roll outChallenges in roll out

Cervical Cancer Worldwide

• 500,000 new invasive cervical cases/500,000 new invasive cervical cases/yearyear

• 270,000 deaths270,000 deaths– 80% in developing countries 80% in developing countries

where it is the first cause of cancer where it is the first cause of cancer death in womendeath in women

• 1.4 million women1.4 million women with clinical cervical with clinical cervical precancer/cancerprecancer/cancer

Cervical Cancer Kenya

• Age standardized incidence rate of cervical Age standardized incidence rate of cervical cancer is cancer is 28.728.7/100,000 women per year /100,000 women per year (compared to 42.7 in Eastern Africa and 16.2 (compared to 42.7 in Eastern Africa and 16.2 in the world) in the world)

– Cervical cancer is the most common cancer Cervical cancer is the most common cancer compared to other cancers among women of all compared to other cancers among women of all agesages

– Cervical cancer is the second most common Cervical cancer is the second most common cancer compared to other cancers among cancer compared to other cancers among women aged 15-44 years of age in Kenyawomen aged 15-44 years of age in Kenya

GLOBAL INCIDENCE OF CERVICAL CANCER PER 100,000 PER YEAR

• Cervical cancer incidence and mortalityCervical cancer incidence and mortality

– Annually, 2,354 women aged 15-65 develop Annually, 2,354 women aged 15-65 develop cervical cancer (Globocan)cervical cancer (Globocan)

– 65% (1,524) die of the disease65% (1,524) die of the disease

– 600,000 women may have cervical dysplasia 600,000 women may have cervical dysplasia in Kenya – estimate as <1% of women have in Kenya – estimate as <1% of women have Pap smearsPap smears

Epidemiology - KenyaEpidemiology - Kenya

Cervical Cancer Occurs Despite Established Screening Cervical Cancer Occurs Despite Established Screening Programs Example of EuropePrograms Example of Europe

CountryCountry

RecommendatioRecommendationn

% % RegularlRegularl

y y ScreeneScreene

dd

Age Age Range Range (Years)(Years)

IntervaInterval l

(Years)(Years)

FinlandFinland11 3030––6060 55 9393

EnglandEngland11 2525––6464 33––55 8383

SwedenSweden11 2323––6060 33 8383

BelgiumBelgium22 2525––6464 33 7878

The The NetherlandsNetherlands11 3030––6060 55 7777

DenmarkDenmark11 2323––5959 33 7575

FranceFrance11 2525––6565 33 6969

ItalyItaly11 2525––6464 33 5353––7474

GermanyGermany11 2020––8585 11 5050

SpainSpain22 2525––6565 33 2727

Cervical Cancer Cervical Cancer Mortality/100,000Mortality/100,00033

Cervical Cancer Cervical Cancer Incidene/100,000Incidene/100,00033

3.03.0 6.26.2

5.15.1 10.510.5

5.65.6 10.910.9

6.26.2 12.812.8

3.83.8 9.49.4

8.68.6 16.316.3

5.45.4 13.613.6

4.04.0 11.611.6

7.17.1 14.714.7

3.63.6 10.310.3

Cervical CancerCervical Cancer

• It killsIt kills

• It hurtsIt hurts

• It smellsIt smells

• Only affectsOnly affects

womenwomen

Adenocarcinoma of the cervix

HPV- A necessary cause for Cervical HPV- A necessary cause for Cervical CancerCancer

• Bosch et al Bosch et al Analysis of 932 specimens from women in 22 Analysis of 932 specimens from women in 22

countries indicated prevalence of HPV DNA in countries indicated prevalence of HPV DNA in cervical cancers worldwide = 99.7%.cervical cancers worldwide = 99.7%.22

•>100 types identified>100 types identified• ~30–40 anogenital~30–40 anogenital

•~15–20 oncogenic ~15–20 oncogenic Most common in ICC 16; 18; 33;31; Most common in ICC 16; 18; 33;31; 35;45;52;58;35;45;52;58;

Virion assemblyVirion assemblyViral DNA replicationViral DNA replication

Virus Virus infectioninfection

Infectious virions shedInfectious virions shed

Virus Virus introducedintroducedthrough through foreign bodyforeign bodyor or microabrasionmicroabrasion

Late HPV proteinLate HPV proteinproductionproductionL1 & L2L1 & L2

Muñoz N, Bosch FX, de Sanjosé, et al. N Engl J Med. 2003;348:518–527. 2. Walboomers JM, Jacobs MV, Manos MM, et al. J Pathol. 1999;189:12–19.

Harald zur Hausen nobel prize in 2008Harald zur Hausen nobel prize in 2008

• Press ReleasePress Release

• 6 October 20086 October 2008

• The Nobel Assembly at Karolinska Institutet has today decided to award has today decided to award The Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine for 2008 with one half tofor 2008 with one half to

• Harald zur HausenHarald zur Hausen

• for his discovery of for his discovery of "human papilloma "human papilloma viruses causing cervical cancer"viruses causing cervical cancer"

• and the other half jointly toand the other half jointly to

• Françoise Barré-Sinoussi and Luc Françoise Barré-Sinoussi and Luc MontagnierMontagnier

• for their discovery of for their discovery of "human "human immunodeficiency virus"immunodeficiency virus"

• In 1984, he cloned HPV16 and 18 In 1984, he cloned HPV16 and 18 from patients with cervical from patients with cervical cancer. cancer.

Hela cells from Henrietta Lacks: slave descendant Hela cells from Henrietta Lacks: slave descendant contribution to Cervical cancer vaccinecontribution to Cervical cancer vaccine

• Henrietta Lacks died on this day in 1951, aged 31, and Henrietta Lacks died on this day in 1951, aged 31, and was buried in an unmarked grave, but her contribution was buried in an unmarked grave, but her contribution to medicine is possibly greater than any other to medicine is possibly greater than any other individual in history.individual in history.

• The tobacco farming mum-of-five was a descendant of The tobacco farming mum-of-five was a descendant of slaves and died of cervical cancer in a segregated slaves and died of cervical cancer in a segregated ward at John Hopkins Hospital, ward at John Hopkins Hospital,

• But research on Henrietta's cancer cells - has helped But research on Henrietta's cancer cells - has helped save countless lives.save countless lives.

• As well as breakthroughs in polio, Aids and IVF, the As well as breakthroughs in polio, Aids and IVF, the cells have helped develop the cervical cancer vaccine, cells have helped develop the cervical cancer vaccine, shed light on TB and salmonella and pushed forward shed light on TB and salmonella and pushed forward gene therapy and stem cell techniques.gene therapy and stem cell techniques.

• Her cells were the first to have their DNA mappedHer cells were the first to have their DNA mapped

Hela cells from Henrietta Lacks:Hela cells from Henrietta Lacks:

• Known as HeLa cells - taken from the first letters of Henrietta's names - they Known as HeLa cells - taken from the first letters of Henrietta's names - they are still used in most labs across the globe and have made BILLIONS for are still used in most labs across the globe and have made BILLIONS for the drugs industry.the drugs industry.

• The incredible story began in 1951, as Henrietta neared death. A small The incredible story began in 1951, as Henrietta neared death. A small sample of tissue was taken from the malignant tumour - standard practice at sample of tissue was taken from the malignant tumour - standard practice at the time.the time.

• Researchers, led by Dr George Gey, were astonished to see the cells grew Researchers, led by Dr George Gey, were astonished to see the cells grew at incredible speeds, and they did not die. Gey discovered the HeLa cells at incredible speeds, and they did not die. Gey discovered the HeLa cells were cancerous, yet also had characteristics of healthy human cells.were cancerous, yet also had characteristics of healthy human cells.

• They were easy to grow, simple to use and were the first so-called "immortal They were easy to grow, simple to use and were the first so-called "immortal cell lines" in science - a perfect test material for medical treatments and new cell lines" in science - a perfect test material for medical treatments and new drugsdrugs

• The same quality that made them so deadly to Henrietta made them ideal The same quality that made them so deadly to Henrietta made them ideal for research.for research.

HPV L1 VLP Subunit VaccinesHPV L1 VLP Subunit Vaccines

• Composed of virus-like particles Composed of virus-like particles (VLPs)(VLPs)

• Expressed via recombinant yeast Expressed via recombinant yeast or viral vectors or viral vectors – The L1 protein self assembles into The L1 protein self assembles into

empty capsids or VLPs that are empty capsids or VLPs that are morphologically and antigenically morphologically and antigenically almost identical to native vironsalmost identical to native virons

Ref: Stanley 2006

54.6

15.8

3.7 3.5 4.3 3.2 2.5

0

10

20

30

40

50

60

16 18 45 31 33 58 52HPV type

% o

f all

case

sSystematic review: Smith et al.

7 most common HPV types in 14,547 invasive cervical cancer cases

HPV 16-18 vaccine could

potentially prevent ~70%

of cervical cancer

Smith et al., in press, Int J Cancer.Smith et al., in press, Int J Cancer.

HPV and Cervical CancerHPV and Cervical CancerPutting Risk in PerspectivePutting Risk in Perspective

• Risk of cervical cancer if HPV 16 +ve Risk of cervical cancer if HPV 16 +ve compared to HPV 16 -ve is 434compared to HPV 16 -ve is 434

• Risk of lung cancer in white US male smoker Risk of lung cancer in white US male smoker vs none smoker is 8vs none smoker is 8

• Risk of breast cancer in women on HRT in the Risk of breast cancer in women on HRT in the Womens Health Initiative is 1.3Womens Health Initiative is 1.3

Risk with Specific HPV TypeRisk with Specific HPV Type

HPV TypeHPV Type CancerCancer ControlControl OROR

1616 5353 33 434434

1818 1111 11 248248

4545 44 0.50.5 197197

3131 33 0.60.6 123123

5252 22 0.20.2 200200

3333 22 0.20.2 373373

Munoz et al 2003 NEMJ

Quadrivalent Prophylactic VaccineQuadrivalent Prophylactic VaccineGardasilGardasil

• Protocol 007 (2000-04) phase IIb, 013 & 015 (2001-07) phase III conductedProtocol 007 (2000-04) phase IIb, 013 & 015 (2001-07) phase III conducted

HPV 6 & 11 against genital wartsHPV 6 & 11 against genital warts

HPV 16 & 18 Ca cervixHPV 16 & 18 Ca cervix

• Study Population: 18,174 women age 16-26Study Population: 18,174 women age 16-26– 157 sites, 24 countries America, Europe, Asia157 sites, 24 countries America, Europe, Asia

• 0-4 lifetime sex partner0-4 lifetime sex partner

• Drug schedule month 0, 2 & 6Drug schedule month 0, 2 & 6

• OutcomeOutcome– HPV genital infection (PCR & Serology)HPV genital infection (PCR & Serology)– CINCIN– VINVIN– Invasive vulval diseaseInvasive vulval disease– Neutralizing type specific anti HPV antibodyNeutralizing type specific anti HPV antibody

Gardasil- Merck VaccineGardasil- Merck Vaccine

Outcome Cervical LesionsOutcome Cervical Lesions

Among at risk women immunized per protocol, vaccine efficacy was 98% in Among at risk women immunized per protocol, vaccine efficacy was 98% in preventing HPV-16 & 18 related HGILpreventing HPV-16 & 18 related HGIL

HPV relHPV relaated cervical lesionsted cervical lesions

Disease assoc with the 4 vaccine types among HPV naïve women was Disease assoc with the 4 vaccine types among HPV naïve women was ZERO in the vaccinated and 52 placeboZERO in the vaccinated and 52 placebo

Efficacy 100%Efficacy 100%

Cross protectionCross protection

Disease associated with 10 non vaccine type HPV seen in 62 placebo vs. Disease associated with 10 non vaccine type HPV seen in 62 placebo vs. 38 vaccine38 vaccine

Efficacy 38%Efficacy 38%

HPV 18 related HPV types vaccine efficacy (15 placebo vs 8 vaccinated) HPV 18 related HPV types vaccine efficacy (15 placebo vs 8 vaccinated)

efficacy 46%efficacy 46%

HPV 16 related non vaccine HPV types disease assoc. 48 placebo vs 26 HPV 16 related non vaccine HPV types disease assoc. 48 placebo vs 26 vaccinevaccine

Efficacy 45%Efficacy 45%

Anogenital WartsAnogenital Warts

•HPV types 6 & 11 responsible for >90% of anogenital warts

• Estimated lifetime risk of warts~~ 10%

•External warts very contagious Infectivity>75%

Vulval LesionsVulval Lesions

• Per protocol populationPer protocol populationWomen HPV negative type 16 & 18 serology and PCR Women HPV negative type 16 & 18 serology and PCR

through vaccine months, received all 3 dosesthrough vaccine months, received all 3 doses

– 15 women with histology proved VIN 2-3 associated 15 women with histology proved VIN 2-3 associated with HPV 16 & 18 in placebo arm none in vaccine with HPV 16 & 18 in placebo arm none in vaccine armarm

• Efficacy for genital lesions was 100% in this populationEfficacy for genital lesions was 100% in this population

– Intent to treat population vaccine efficacy for vulval Intent to treat population vaccine efficacy for vulval lesions was 49%lesions was 49%

• Vaccinated women with prior HPV infection were not Vaccinated women with prior HPV infection were not protected from diseaseprotected from disease

CervarixCervarixHPV 16 & 18HPV 16 & 18

• Population 18,644 women age 15-25Population 18,644 women age 15-25– < 6 lifetime partners; 75% with one sex partner in last 6/12< 6 lifetime partners; 75% with one sex partner in last 6/12– Excluded pregnancy breastfeeding, prior +ve CIN; HIVExcluded pregnancy breastfeeding, prior +ve CIN; HIV

• Dose schedule 0, 1 & 6 monthsDose schedule 0, 1 & 6 months

• OutcomeOutcome– Fully protective against lesions caused by specific HPV type in Fully protective against lesions caused by specific HPV type in

vaccine if negative serology at enrollmentvaccine if negative serology at enrollment– Adverse events mostly injection siteAdverse events mostly injection site

CervarixCervarixIntent to treatIntent to treat

OutcomeOutcome VaccineVaccine PlaceboPlacebo EfficacyEfficacy

16 CIN 2+16 CIN 2+ 11 1515 9393

18 CIN 2+18 CIN 2+ 11 66 8383

16 CIN 1 +16 CIN 1 + 22 1818 8989

18 CIN 1+18 CIN 1+ 11 1111 9191

SafetySafety

• Adverse Events were similar for both vaccinesAdverse Events were similar for both vaccines

• Vaccine related 1% > among vaccinated vs Vaccine related 1% > among vaccinated vs placeboplacebo

– Fever (10%); Fever (10%); – nausea (4%); nausea (4%); – dizziness (3%); dizziness (3%); – injection site pain (84%),injection site pain (84%),– erythema at injection site (25%); erythema at injection site (25%); – pruritus (3%)pruritus (3%)

• SAE one person experience bronchospasms and 2 asthma not SAE one person experience bronchospasms and 2 asthma not clear if vaccine relatedclear if vaccine related

• Gardasil one thromboeimbolism event in vaccine armGardasil one thromboeimbolism event in vaccine arm• 2 Guillain Barre Syndrome HPV only2 Guillain Barre Syndrome HPV only

1

10

100

1000

10000

month 0 month 7 month 12month 18[M25-M32][M33-M38][M39-M44][M45-M50][M51-M53]

log (ELU/ml)

Months follow up timeHPV-001 HPV-007

100%100%

99%99%99%99.7%

100%

100%

10%

Vaccine HPV-18 IgG% seropositive

GSK Sustained seropositivity andGSK Sustained seropositivity andHigh antibody levels up to 4.5 yearsHigh antibody levels up to 4.5 years

HPV-18

NaturalInfection

Ge

om

etr

ic M

ean

Tit

er

(mM

U/m

L)

HPV 16 L1 VLP Vaccine HPV 16 L1 VLP Vaccine

Placebo recipients who were HPV 16 Placebo recipients who were HPV 16 Sero(+)/PCR(-) at Day 1 Sero(+)/PCR(-) at Day 1

Month Since Enrollment0 7 12 18 30 42 48

1

10

100

1000

20003000

Vaccination

MERCK Protection After Plateau of VLP AntibodyMERCK Protection After Plateau of VLP AntibodyTiters Suggests Long Term ProtectionTiters Suggests Long Term Protection

Merck data, Mao et al. 2006

Prophylactic HPV VaccinesProphylactic HPV Vaccines

• GardasilGardasil® ® : : Merck & Co., Inc. Merck & Co., Inc. – Quadrivalent vaccine (types 6, 11, 16, 18)Quadrivalent vaccine (types 6, 11, 16, 18)– 3 doses (0, 2, and 6 months)3 doses (0, 2, and 6 months)– Approved by FDA in June 2006 Approved by FDA in June 2006

• Recommended by the US Advisory Committee on Immunization Recommended by the US Advisory Committee on Immunization Practices for 11 and 12 yr old girlsPractices for 11 and 12 yr old girls

• Catch-up vaccination for 13-26 yr oldsCatch-up vaccination for 13-26 yr olds

• CervarixCervarix®®: GlaxoSmithKline Biologicals: GlaxoSmithKline Biologicals– Bivalent vaccine (types 16, 18)Bivalent vaccine (types 16, 18)– 3 doses (0, 1, and 6 months)3 doses (0, 1, and 6 months)– Approved by FDA Approved by FDA

HPV Types by Cervical Status: HPV Types by Cervical Status: Impact of 16/18 VaccineImpact of 16/18 Vaccine

0%

20%

40%

60%

80%

100%

Invasive Cancer HSIL LSIL

~70%

~50%

~14-25%

HP

V T

ype

Sp

ecif

ic P

reva

len

ce in

All

Cas

es

ICC data: ICC data: Clifford et al. Clifford et al. Br J CancerBr J Cancer. 2003;88:63-73.. 2003;88:63-73.HSIL data: HSIL data: Clifford. Clifford. Br J CancerBr J Cancer. 2003;89:101-105.. 2003;89:101-105.LSIL data: Clifford et al. LSIL data: Clifford et al. Cancer Epidemiol BiomarkersCancer Epidemiol Biomarkers.. 2005;14:1157-1164. 2005;14:1157-1164.

Analysis of MERCK Prophylactic Efficacy Analysis of MERCK Prophylactic Efficacy Against HPV 6, 11, 16, or 18-Related External Against HPV 6, 11, 16, or 18-Related External

Anogenital or Vaginal Lesions (EGL)Anogenital or Vaginal Lesions (EGL)

VaccineVaccine(N = 8,799)(N = 8,799)

PlaceboPlacebo(N = 8,800)(N = 8,800)

nnNumber Number of casesof cases Rate*Rate* nn

Number Number of casesof cases Rate*Rate* Observed Observed

efficacyefficacy 95% CI95% CI

HPV HPV 6,11,16,18-6,11,16,18-Related Related EGLEGL

2,2202,220 33 0.10.1 2,2182,218 3333 0.80.8 90.9%90.9% (71.1, 98.2)(71.1, 98.2)

By HPV TypeBy HPV Type

HPV 6-Related HPV 6-Related 1,2651,265 33 0.10.1 1,2521,252 2424 1.01.0 87.7%87.7% (59.4, 97.6)(59.4, 97.6)

HPV 11-RelatedHPV 11-Related 1,2651,265 00 0.00.0 1,2521,252 66 0.20.2 100.0%100.0% (15.7, 100.0)(15.7, 100.0)

HPV 16-RelatedHPV 16-Related 951951 00 0.00.0 918918 44 0.20.2 100.0%100.0% (<0.0, 100.0)(<0.0, 100.0)

HPV 18-RelatedHPV 18-Related 1,7471,747 00 0.00.0 1,7581,758 33 0.10.1 100.0%100.0% (<0.0, 100.0)(<0.0, 100.0)

Subjects are counted once in each applicable endpoint category. A subject may appear in more than one category.*Cases per 100 person years at risk.N = Number of subjects randomized to the respective vaccination group who received at least 1 injection and were seronegative and PCR negative to the relevant HPV type at enrollment; n = Number of subjects in the given population with at least 1 follow-up visit following 30 days after Day 1; VIN = vulvar intraepithelial neoplasia; VaIN = vaginal intraepithelial neoplasia.

Subjects Previously Exposed to ≥1 Vaccine HPV Type at Day 1

MERCK Gardasil Approval SpecificsMERCK Gardasil Approval Specifics

• US FDA approved for 9-26 yr old females in June ‘06

ACIP recommended June ‘06 for:- routine vaccination of 11-12 yr old- catch up vaccination 13-26 yr old- 9-10 yr old vaccination at physician’s

discretion- inclusion in Vaccines for Children

program

• Australia approved for 9-26 yr old females 9-15 yr old boys

HPV infection is the main cause HPV infection is the main cause of cervical cancer’of cervical cancer’

Ever heard of HPV

0

10

20

30

40

50

60

70

80

1 2 3 4 5

Responses

%

1="TRUE"

2="FALSE"

3="Not sure"

4="never heard"

Waller et al. Sexually Transmitted Infections, 2003

SummarySummary

• Potential to markedly reduce incidence and mortality of Potential to markedly reduce incidence and mortality of cervical cancercervical cancer– Primary data demonstrates immune response with neutralizing Primary data demonstrates immune response with neutralizing

antibodies in older womenantibodies in older women

• HPV vaccines are highly effectiveHPV vaccines are highly effective

– Only if the woman has no prior infection with specific HPV type in Only if the woman has no prior infection with specific HPV type in vaccinevaccine

– Preliminary data on safety & immunogenicity among HIV+ve Preliminary data on safety & immunogenicity among HIV+ve childrenchildren

– Will need to continue screening as vaccine is not 100% cover for Will need to continue screening as vaccine is not 100% cover for all HR HPV typesall HR HPV types

• ChallengesChallenges– CostCost, reaching youth, reaching youth

The Unscreened Woman—Will these be The Unscreened Woman—Will these be the unvaccinated women?the unvaccinated women?

Poor

Uneducated

Ethnic Minority

Learning Disabled

Lives in a Developing Country

35

GAVI Prioritization/WHO PrequalificationGAVI Prioritization/WHO Prequalification

• Global Alliance for Vaccine ImplementationGlobal Alliance for Vaccine Implementation

• 72 of the world’s most impoverished nations are 72 of the world’s most impoverished nations are “GAVI-eligible” countries“GAVI-eligible” countries

• HPV Vaccines given high priorityHPV Vaccines given high priority

• Included in proposed GAVI packageIncluded in proposed GAVI package

• Final prioritization completedFinal prioritization completed

• Funding decision pendingFunding decision pending

• WHO prequalification achieved end of 2009WHO prequalification achieved end of 2009

36

GARDASILGARDASIL®® Access Program Access Program• Donation of 3 million doses over panned 5-year periodDonation of 3 million doses over panned 5-year period

• ““GAVI-eligible” countriesGAVI-eligible” countries

• Overseen by Axios Healthcare Development; US Non-profit organizationOverseen by Axios Healthcare Development; US Non-profit organization

• Overseen by Advisory Board of Health ExpertsOverseen by Advisory Board of Health Experts– Wide geographic representationWide geographic representation– Medicine, gynecology, vaccination, women’s health, global health, health Medicine, gynecology, vaccination, women’s health, global health, health

and developmentand development

• Eligible institutionsEligible institutions– Government institutionsGovernment institutions– NGOs or charitable organizations involved in vaccination services or cancer NGOs or charitable organizations involved in vaccination services or cancer

managementmanagement– Academic institutionsAcademic institutions

• Letter of support from MOH/MOH waiver if not registered in country of interestLetter of support from MOH/MOH waiver if not registered in country of interest

• Information/application at: Information/application at: – GARDASILaccess@AccessToTreatment.orgGARDASILaccess@AccessToTreatment.org

http://www.gardasilaccessprogram.org/

37

GARDASlLGARDASlL®® Access Program Access Program

• Since inception, organizations and institutions in Since inception, organizations and institutions in 20 low income countries including:20 low income countries including:– Cameroon, Ghana, Kenya, Lesotho, Nigeria, Tanzania and Cameroon, Ghana, Kenya, Lesotho, Nigeria, Tanzania and

Uganda have been approved to receive more than 1 Uganda have been approved to receive more than 1 million doses of GARDASILmillion doses of GARDASIL®®

– To gain operational experience in the design and implementation To gain operational experience in the design and implementation of HPV vaccination projects in their countries of HPV vaccination projects in their countries

38

Merck Investigator Initiated Study Merck Investigator Initiated Study ProgramProgram

• Small grants for investigator-initiated research Small grants for investigator-initiated research proposalsproposals

• Areas of interestAreas of interest

• Developing world-specific areas of interestDeveloping world-specific areas of interest

Thank youThank you

Nelly Mugo, KNHNelly Mugo, KNH