HPV vaccination importance in Lesotho
65
Preventing Cervical Cancer in Lesotho Sejojo Phaaroe Principal Biomedical Scientist, and a Cytologist of International Academy of Cytology- # 6467 Health Research & Laboratory Services Cytopathology unit – Lesotho
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Transcript of HPV vaccination importance in Lesotho
Preventing Cervical Cancer in Lesotho
Sejojo Phaaroe
Principal Biomedical Scientist, and a
Cytologist of International Academy of Cytology- # 6467
Health Research & Laboratory Services
Cytopathology unit – Lesotho
Learning out come • Learn and share: comprehensive review
of international conventions on cervical cancer prevention & Lesotho ‘ s response
• Cervical Cancer Prevention strategies
• Aetiology of cervical cancer development and role of HPV
• HPV What is it ?
• HPV VACCINE – Gardasil , What is it?
• EPI challenges:
• HPV AND VACCINE .
There is no need for you to catch the ball if you do not know where the goal is
-
Comprehensive review of international
conventions on RH cancers
IUAC ( International union Against Cancer) IUCR ( International Union on Cancer Research ) IAC (International Academy of Cytology)
WHO (2002) - …AU ( Maputo SRH declaration)
…SADAC
…Lesotho Road map ( Maternal Mortality SRHR)
AFROX declaration (2007)
WHO, 2002
1- WHO/ MOHSW – sponsor a baseline study CACX 2006
2. Lesotho RH Cancer Screening Guidelines
3. Implementation of prevention guidelines
Gardasil ACCESS : 2009 Pilloting Leribe and Mohale’s Hoek
African Conference on Cervical Cancer Prevention Sept. 2010
Lobbying for Support from African Policymakers and Parliamentarians: The Uganda Experience
Honorable Sarah Nyombi
Member of Parliament, Uganda
• •Lesotho strategy: Involve policymakers (parliamentarians).
• • Financial resources for new technologies (i.e., HPV DNA testing at point of care, vaccine).
• • Training and education.
• • Screening—VIA/cytology/DNA/colposcopy (pilot studies and full-scale HPV Vaccine rollout).
WHO- Public Health
(Stjernsward, 2007)
Radiology,
urology
Oncology,
palliative
care ? Etc
problem
Lab
tests?
Distribution Of Common Cancer Between the Sexes IN Southern Africa to include Lesotho
Males
Lung
Prostate
Stomach
Liver
Colorectal
Oesophagus
Females
Cervical
Breast
Lung
Stomach
Colorectal
Island Hospice Service
Cancer definition Cancer is a neoplastic
proliferation of abnormal cells, invading surrounding tissue and giving distance metastases
Cancer of the cervix 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 ( later )
Signs and symptoms/ clinical presentation
• Early signs:
• Abnormal vaginal bleeding which could be
• Intermenstrual
• Post coital bleeding
• Post menopausal bleeding
• Watery offensive vaginal discharge
• The cervix is friable , hard with contact bleeding on examination( the dysplastic cells have poor cohesiveness, so the underlining vascular system in the lamina propriae become exposed.)
Late signs
• Pain
• Dyspareuria(pain during intercourse)
• Urinary symptoms: frequency in urination
• Dysurea
• Hematuria
• Vesico-vaginal and or recto-vaginal fistula
• Anaemia, Cachexia
• Bone pain, due to metastases
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
• 80% of cervical cancer cases in the developing world
• How big is the problem
Response?
Response?
I see how big it is but there is
nothing I can do!
Response!!!!
½ million women
die each year , lets
mount prevention
plans
These are our People : Lets Base Programs on the Needs of our People
R108 000 COST OF TREATMENT IN RSA in
2006 study
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
2007 Projection
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 Education , BCC, condom distribution ,
and awareness campaigns
PAP smear screening
HPV DNA testing
Direct Visual Inspection Acetic acid –VIA
VIAM
HPV vaccine- CAMPAIGN
National stake holders
Education/Information-Magnitude of cancer
Gyaenacology,
Oncology,
Radiology,
Pharmacy etc
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
Chiefs, local
government,
village councils,
NETWORKS
LEGAL
SYSTEMS, Policy
makers,
International
conventions,
Regional
strategies
EMPLOYMENT
FORCE/
Government
Institutions
Insurance Levy,
Businesses &
Industry
Technology
INCUBATION
CENTRES,
SMME’s , Joined
Bilateral
commissions/
agreements
CYTOPATHOLOGY
BIOMEDICAL
SCIENCE
RESEARCH LAB
is the central
organ
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
LBCN
Etiological factors behind cancer of the Cervix
• women -Early coitus
• Multiparious women
• Multisexual partners
• It varies with race [genetic susceptibility ,etc]
• High in low socio-economic stata [malnutrition,poor health facilities]
• Poor hygiene[smegma factor]
• Sperm factor[acridine histones]
• Women with boyfriends with CA. penis
.Hormonal contraceptives /preparations like depo [Stern et al 1977]
• STI’s- infection, etc.
• Viral HIV,
• Viral HPV,
• Viral H Herpes
• Smoking [TARR/hetero]
• Alcohol drinking
• Drugs (Diethylstilbestrol-DES),cyclophosphamide
• Pelvic irradiation.
• History of cancer from other sites e.g uterus, colon.
81% ?
Human Papillomavirus (HPV) and the Vaccine
•
• HPV is the most common sexually transmitted infection
• DNA VIRUS
• Causes 99% of cervical cancer cases worldwide
• 100 different types of HPV, 40 types affect the genital tract
• Types 16 & 18 cause 80% of cervical cancer cases
Disease Burden HPV types 6, 11, 16, & 18
6, 11, 16, and 18
70% of cervical cancer, AIS, CIN 3, VIN 2/3, and VaIN 2/3 cases
50% of CIN 2 cases
16 and 18
Approximate Disease Burden HPV Type
35%–50% of all CIN 1, VIN 1, and VaIN 1 cases
90% of genital warts cases
GARDASIL® (Quadrivalent Human Papillomavirus [HPV Types 6, 11, 16, 18] Recombinant Vaccine)
Classification of Histological Findings
CIN1 Normal
CIN 1
(condyloma)
CIN 1
(mild
dysplasia)
CIN 2
(moderate
dysplasia)
CIN 3
(severe dysplasia/CIS)
Invasive
Cancer
Histology of
squamous
cervical
epithelium1
Basal cell
Basal membrane
CIN caused by HPV can clear without treatment; however, rates of regression are dependent on grade of CIN.
Screening for cervical cancer
Dr. George N. Papanicolaou, who devised the "Pap" smear test for cancer,
examines a slide in his laboratory in 1958.
NOVA, PBS
HPV-DNA FISH
GARDASIL® (Quadrivalent Human Papillomavirus [HPV Types 6, 11, 16, 18] Recombinant Vaccine)
• Area of metaplasia at squamocolumnar junction
• ~99% of HPV-related genital cancers arise within the transformation zone.
• The Pap test obtains cells from the transformation zone for cytology screening.
1. Castle PE. J Low Genit Tract Dis. 2004;8:224–230. 2. American Cancer Society. Prevention and early detection. Pap test.
July 2006; Available at; http://www.cancer.org/docroot/PED/content/PED_2_3X_Pap_Test.asp?sitearea=PED
Cervical Transformation Zone
GARDASIL® (Quadrivalent Human Papillomavirus [HPV Types 6, 11, 16, 18] Recombinant Vaccine)
Appearance of the Normal Cervix on VIAM
1. Sellors JW, Sankaranarayanan R, eds. Lyon, France: International Agency for Research on Cancer; 2003. Reprinted
from Colposcopy and Treatment of Cervical Intraepithelial Neoplasia. A Beginner’s Manual with permission of the
International Agency for Research on Cancer, World Health Organization.
GARDASIL® (Quadrivalent Human Papillomavirus [HPV Types 6, 11, 16, 18] Recombinant Vaccine)
Cervical Intraepithelial Neoplasia- VIAM
CIN 1 CIN 2 CIN 3
VIA-
GARDASIL® (Quadrivalent Human Papillomavirus [HPV Types 6, 11, 16, 18] Recombinant Vaccine)
Invasive Cervical Carcinoma
From IARC, 2003.1
Interpretation • Pick up age for HPV _>19 -44 yrs
• Pick up age for other specific infections= ->19-44
• Peak age for CIN1= 20-39 yrs
• Peak age CIN2 = 30-49 yrs • Peak age for CIN3= 35-44 yrs
• Pick up for invasive cancer= 30- 59 CYTOLOGICALLY
• Peak age for confirmed invasive cancer = 40-59 yrs
• Risk of women developing cancer= (36:4610)
• Risk = 1: 128 women
• ASIR: 66,7 : 100 000
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 more than 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
• when we first stated vaccinating , 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
54
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 AIS R
ela
ted 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
55
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
Rela
ted C
ases
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
GARDASIL® [Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine]
n=7,741
n=7,769
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
56
GARDASIL® (Quadrivalent Human Papillomavirus [HPV Types 6, 11, 16, 18] Recombinant Vaccine)
HPV and Anogenital Warts
HPV 6 and 11 responsible
for >90% of anogenital warts
Infectivity >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.
57
Genital & Anal warts
58
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.
59
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
60
41
83
91
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
Rela
ted C
ases
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
99%
Efficacy
95%
Efficacy
n=7,861
n=7,858
n=7,899
n=7,897
CIN = cervical intraepithelial neoplasia; AIS = adenocarcinoma in situ.
GARDASIL® [Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine]
Lesotho HPV Vaccination Strategy
• Application for Gardasil access 2008
• Establishing National HPV Guidelines, action plan, implementation strategy
• The HPV Vaccine was be piloted in Leribe and Mohales’Hoek districts
• Target population: Females Aged 9-18 years, later 9-13 yrs
• School-based was used Estimated Starting period : February 2009
• Follow established vaccine distribution system
• Monitoring and evaluation- through current system
EPI Information and Data Flow
• THANK YOU FOR LISTENING
