Lesotho hpv vaccine 2012

Preventing Cervical Cancer in Lesotho

Sejojo Phaaroe

Cervical Cancer Worldwide Disease Burden

• 2nd most common cancer in women worldwide

• Number one cause of cancer-related deaths in women in the developing world

• Annual disease burden

– 493,000 cases

– 273,500 deaths• 90% of cervical cancer cases in the developing world

Base Programs on the Needs of our People

50% of young people between 15 and 24 years of age will DIE within the next 10 years!

Disease Burden in Lesotho

Lesotho Disease Burden

• QEII data

– 1April2006 – 31March2007

– 680 cervical cancer referrals – If 25-33% of population seek out treatment at the national referral hospital then

2000-2800 women may have late stage disease in Lesotho

• Leribe and Mohale’s Hoek Referrals*– 1Jan2005 – 31March2006

– Retrospective analysis of cytology and hystology archives

– Age Standardized Incidence Rate (ASIR) 66.7:100,000 women

*Phaaroe, 2007

Cervical Cancer by Age

90% of cervical cancer cases were in women over age 39

Human Papillomavirus (HPV) Infection• HPV is the most common sexually transmitted infection • Causes 99% of cervical cancer cases worldwide

• 100 different types of HPV, 40 types affect the genital tract

• Types 16 & 18 cause 70% of cervical cancer cases

Cancer definition Cancer is a neoplastic

proliferation of abnormal cells, invading surrounding tissue and giving distance metastases

Cancer of the breast is the neoplastic proliferation of cells and tissues in the breast

Abnormal proliferation starts with the genetic aberration in a single cell genetic material, which grows and give a clone of abnormal cells

A number of factors contribute into the cellular disturbance

Correlation of ASIR rates in Southern Africa COUNTRY ASIR Sited Publication

South Africa 32.1 : 100 000 Freddy Sitas et al

1993 Mali 21.0 : 100 000 Bayo et al 1990 Uganda 43.6 : 100 000 Wabbinga et al 1993 Gambia 13 : 100 000 Bah 1990 Senegal 9 : 100 000 Bah et al 1988 Lesotho 66.7 : 100 000 S. Phaaroe et al 2007 Senegal & Gambia are Moslem areas ( Low in Gambia) Zimbabwe 67:100 000 ( Dr Cronje – Oncology specialist : Sebeta Memorial Lecture LMA AGM 8/7/06

Prevention Strategies PAP smear screening

HPV testing

Direct Visual InspectionDirect Visual Inspection Acetic acid –VIA Acetic acid –VIA

HPV vaccine

Education

FinishedH igh School

Psychological

CounselingConflict

Resolution

Social

Strengthen-Fam ily

Com m unity

Economic

New JobsLegislative (law) Outlaw F irearm s

M ore Prisons/Longer Sentences

W KS ?

H A T IN DO F O L U T IO N

Biological/Medical

Pharm aco-Therapy

National stake holders Education/Information-Magnitude of cancer

Gyaenacology, Oncology, Radiology, Pharmacy etc

Gyaenacology, Oncology, Radiology, Pharmacy etc

FAMILY H, ED, PLANNING & Men’s clinics, private clinics linkage with NGO’S in a health system

FAMILY H, ED, PLANNING & Men’s clinics, private clinics linkage with NGO’S in a health system

Education , Academic centers of excellence & other Research institutions

Education , Academic centers of excellence & other Research institutions

Chiefs, local government, village councils, NETWORKS

Chiefs, local government, village councils, NETWORKS

LEGAL SYSTEMS, Policy makers, International conventions, Regional strategies

LEGAL SYSTEMS, Policy makers, International conventions, Regional strategies

EMPLOYMENT FORCE/ Government Institutions Insurance Levy, Businesses & Industry

EMPLOYMENT FORCE/ Government Institutions Insurance Levy, Businesses & Industry

Technology INCUBATION CENTRES, SMME’s , Joined Bilateral commissions/ agreements

Technology INCUBATION CENTRES, SMME’s , Joined Bilateral commissions/ agreements

CYTOPATHOLOGY BIOMEDICAL SCIENCE RESEARCH LAB is the central organ

CYTOPATHOLOGY BIOMEDICAL SCIENCE RESEARCH LAB is the central organ

Well women groups/ church/ women in Law, every body, Support groups/ men leagues

Well women groups/ church/ women in Law, every body, Support groups/ men leagues

S. Phaaroe M.T

C.T(IAC), MIBMS

PSBH- REPORT Boston University 2005

S. Phaaroe M.T

C.T(IAC), MIBMS

PSBH- REPORT Boston University 2005

LBCN

Disease BurdenHPV types 6, 11, 16, & 18

6, 11, 16, and 186, 11, 16, and 18

70% of cervical cancer, AIS, CIN 3, 70% of cervical cancer, AIS, CIN 3, VIN 2/3, and VaIN 2/3 casesVIN 2/3, and VaIN 2/3 cases

50% of CIN 2 cases50% of CIN 2 cases16 and 1816 and 18

Approximate Disease BurdenApproximate Disease BurdenHPV TypeHPV Type

35%35%––50% of all CIN 1, VIN 1, 50% of all CIN 1, VIN 1, and VaIN 1 casesand VaIN 1 cases

90% of genital warts cases90% of genital warts cases

HPV-Related Disease Development

Clifford GM, Smith JS, Plummer M, Munoz N, Franceschi S. Human papillomavirus types in invasive cervical cancer worldwide: a meta-analysis. Br J Cancer. 2003;88: 63-73.

HPV Type Prevalence Worldwide

High prevalence of HPV 16 in South African women with cancer of the cervix and cervical intraepithelial neoplasia

• Cervical cancer biopsies 82% contained type 16 and 10% type 18 • 56.6% of CIN (cervical intraepithelial neoplaysia) lesions contained type 16

Kay P, Soeter R, Nevin J, Denny L, et al. High prevalence of HPV 16 in South African women with cancer of the cervix and cervical intraepithelial neoplasia. J Medical Virology 2003;71:265-273.

Gardasil®

• Non-infectious, recombinant, quadrivalent vaccine

• Prepared from highly purified virus-like particles (VLPs) of the major capsid protein (L1) protein

• Contains no DNA

• Protects against HPV types 6, 11, 16 & 18

• Three separate IM injections

– 1st dose: at elected date

– 2nd dose: 2 months after the 1st dose

– 3rd doses: 6 months after the 1st dose

• Age indication: females ages 9-26

Gardasil® Registration

• Registered in 100 countries

• U.S., all 27 member countries of the European Union, Mexico, Australia, Taiwan, Canada, New Zealand, and Brazil

• U.S. FDA approval in June 2006

• Africa registration: South Africa, Togo, Chad, Uganda

• 26 million doses distributed worldwide

• 11 million doses distributed in the U.S.

Clinical Trials

• FUTURE I & FUTURE II studies

• Phase III, prospective, double-blind, placebo controlled trials in 29 countries

• Females ages 15 - 26

22

53

0

10

20

30

40

50

60

CIN 2/3 or AIS

GARDASIL Placebo

GARDASIL Is Efficacious Against HPV 16– and 18–Related CIN 2/3 or AISR

elat

ed C

ases

100% Efficacy

16- to 26-year-old females naïve to the relevant vaccine HPV type at enrollment and through 30 days Postdose 3

Over a period of 2 to 4 years Analysis included Protocol 005.

0

CIN = cervical intraepithelial neoplasia; AIS = adenocarcinoma in situ.

GARDASIL® [Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine]

n=8,487

n=8,460

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GARDASIL® (Quadrivalent Human Papillomavirus [HPV Types 6, 11, 16, 18] Recombinant Vaccine)

Cervical Intraepithelial Neoplasia- VIAM

CIN 1 CIN 2 CIN 3

VIA-

24


Invasive Cervical Carcinoma

From IARC, 2003.1

25


Classification of Histological Findings

CINCIN11 NormalNormal

CIN 1CIN 1

(condylo(condyloma)ma)

CIN 1CIN 1

(mild (mild dysplasiadysplasia

))

CIN 2 CIN 2 (moderat(moderat

e e dysplasiadysplasia

))

CIN 3CIN 3

(severe (severe dysplasia/CIS)dysplasia/CIS)

Invasive Invasive CancerCancer

Histology Histology of of squamous squamous cervical cervical epitheliumepithelium11

Basal cell

Basal membrane

CIN caused by HPV can clear without treatment; however, rates of CIN caused by HPV can clear without treatment; however, rates of regression are dependent on grade of CIN.regression are dependent on grade of CIN.

26

27

10

0

2

4

6

8

10

12

VIN 2/3 or VaIN 2/3

GARDASIL Placebo

GARDASIL Is Efficacious Against HPV 6/11/16/18–Related VIN and VaIN

Rel

ated

Cas

es

100% Efficacy

Data available on request from Merck & Co., Inc., Professional Services-DAP, WP1-27, PO Box 4, West Point, PA 19486-0004. Please specify information package 20651717(3)-GRD.

VIN = vulvar intraepithelial neoplasia; VaIN = vaginal intraepithelial neoplasia.

0


n=7,741

n=7,769


Over a period of 2 to 4 years

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HPV and Anogenital Warts HPV 6 and 11 responsible for

>90% of anogenital warts

Infectivity Infectivity >>75%75%

Treatment can be painful and embarrassing.4

Topical and surgical therapies are available for genital warts

Recurrence rates vary greatly.

1. Jansen KU, Shaw AR. Annu Rev Med. 2004;55:319–331. 2. Soper DE. In: Berek JS, ed. Novak’s Gynecology. 13th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2002:453–470. 3. Lacey CJN. J Clin Virol. 2005;32(suppl):S82–S90. 4. Maw RD, Reitano M, Roy M. Int J STD AIDS. 1998;9:571–578. 5. Kodner CM, Nasraty S. Am Fam Physician. 2004;70:2335–2342.

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Genital & Anal warts

30

HPV-Related Disease Development

31

HPV Clearance

In a study of 608 college women, 70% of new HPV infections cleared within 1 year

and 91% within 2 years. Median duration of infection = 8 months Certain HPV types are more likely to persist (eg,

HPV 16 and HPV 18). Women with HIV are unable to clear the infection

Schiffman J Natl Cancer Inst Monogr. 2003;31:14–19. Ho N Engl J Med. 1998;338:423–428.

32

CIN is common in HIV infected women because: HIV infected women likely to have persistent HPV Persistent infection leads to cervical cancer

Do ARTs Lower the Risk of Cervical Cancer? Multiple studies yield mixed results Incidence of cervical cancer appears to be unchanged in

the ART era Those on ART are more likely to have persistent HPV

So, probably no . . . therefore other treatment needed

Cervical Cancer and HIV

33

4 1

8391

0

10

20

30

40

50

60

70

80

90

100

CIN 1, CIN 2/3 or AIS Genital Warts

GARDASIL Placebo

GARDASIL Is Efficacious Against HPV 6/11/16/18–Related Lesions

Rel

ated

Cas

es


Over a period of 2 to 4 years

99% Efficacy

95% Efficacy

n=7,861

n=7,858

n=7,899

n=7,897

CIN = cervical intraepithelial neoplasia; AIS = adenocarcinoma in situ.


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27% of subjects had evidence of prior exposure to or ongoing infection with at least 1 of the4 vaccine HPV types.

20%

Subjects Exposed to Any Vaccine HPV Type at Enrollment

73% of subjects were naïve to all 4 vaccine HPV types. Among subjects who were positive to a vaccine HPV type, most were

positive to only 1 type. Exclusion criteria: 6 or more sexual partners

Baseline HPV Status


Efficacy Studies—Combined Population

Naïve to all 4 types

Positive to 1 type

Positive to 2 types

Positive to 3 types

Positive to 4 types

93% of subjects were naïve to ≥3 vaccine HPV types (6, 11, 16, or 18) at enrollment.

1.2%

0.1%

6%

73%

Data available on request from Merck & Co., Inc., Professional Services-DAP, WP1-27, PO Box 4, West Point, PA 19486-0004. Please specify information package 20651717(4)-GRD.

35

*Evaluated only the HPV 16 L1 VLP vaccine component of GARDASIL.GMT = Geometric mean titer; cRIA = Competitive radioimmunoassay.

684 684 663 649 609 533 481

680 680 661 638 604 532 489

Number of Subjects

Months Since Enrollment

Adapted from Mao C, Koutsky LA, Ault KA, et al. Obstet Gynecol. 2006;107:18–27.

GARDASIL Maintained Type-Specific,Neutralizing Antibody Responses

0 7 12 18 30 42 481

10

100

1,000

3,0005,000

Ser

um c

RIA

GM

T*,

mM

U/m

L

GARDASIL (Per Protocol) Per-Protocol Placebo

Vaccination

Ph II–P005 Proof of Principle 16- to 23-year-old women

The durationof protectionof GARDASIL is unknown beyond 48 months.


36

0

500

1,000

1,500

2,000

2,500

3,000

3,500

16 18 6 11 16 18 6 11

Early On Time Late

Variation in Dosing Regimen for GARDASIL

*Dose 2 (Postdose 1): Early = 36–50 days Postdose 1; On Time = 51–70 days; Late = 71–84 days.†Dose 3 (Postdose 2): Early = 80–105 days Postdose 2; On Time = 106–137 days; Late = 138–160 days.

Summary of Geometric Mean Titers (GMTs)

Anti-HPV Types

Variability in Dose 2*

Variability in Dose 3†

GM

Ts

1 M

onth

Pos

tdos

e 3

Gardasil® Access Program• Merck donates 3 million doses

– U.S. price = $125/dose

• For GAVI-eligible countries

• This is NOT a clinical trial or and experiment

• Providing access to a new & expensive vaccine for developing countries

• Free doses will go to those countries that can demonstrate implementation projects

Lesotho Strategy

• The HPV Vaccine will be piloted in Leribe and Mohales’Hoek districts

• Target population: Females Aged 9-18 years

• School-based and Facility Based strategies will be used facilitated by the public health nurses with the assistance of the hospital staff

• Estimated Starting period : February 2009

• Follow established vaccine distribution system

• Monitoring and evaluation- through current system

EPI Information and Data Flow

Health & Medicine

Lesotho hpv vaccine 2012