1. 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

2. 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:

3. There is no need for you to catch the ball if you
do not know where the goal is
-

4. 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)
WHO, 2002
 AFROX declaration (2007)

5.  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

6. African Conference on Cervical
Cancer Prevention Sept. 2010

7. Lobbying for Support from African Policymakers and
Parliamentarians: The Uganda Experience
Honorable Sarah Nyombi
Member of Parliament, Uganda

8. YES WE CAN!!!!!

9. • •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).

10. WHO- Public Health
Lab
tests?
Radiology,
urology
Oncology,
palliative
care ? Etc
problem (Stjernsward, 2007)

11. Distribution Of Common Cancer Between the Sexes
IN Southern Africa to include Lesotho
Males Females
 Lung  Cervical
 Prostate  Breast
 Stomach  Lung
 Liver  Stomach
 Colorectal  Colorectal
 Oesophagus

12. 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 )

13. 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.)

14. 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

15. 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

16. • How big is the
problem

17. Response?

18. Response?
I see how big it is but there is
nothing I can do!

19. Response!!!!
½ million women
die each year , lets
mount prevention
plans

20. These are our People : Lets Base Programs
on the Needs of our People
R108 000 COST OF TREATMENT IN RSA in
2006 study

21. Disease Burden in Lesotho

22. 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

23. Cervical Cancer by Age
90% of cervical cancer cases were in women over age 39

25. 2007 Projection

27. 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

28. 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

30. S. Phaaroe
National stake holders C.T(IAC), MIBMS
M.T
PSBH- REPORT Boston
Education/Information-Magnitude of cancer
University 2005
Well women
groups/ church/
Gyaenacology,
women in Law,
Oncology,
every body,
Radiology,
Support groups/
Pharmacy etc
men leagues
Chiefs, local
government,
FAMILY H, ED, CYTOPATHOLOGY village councils,
PLANNING & BIOMEDICAL NETWORKS
Men’s clinics, SCIENCE
private clinics RESEARCH LAB
linkage with is the central Technology
LBCN NGO’S in a health organ INCUBATION
system CENTRES,
SMME’s , Joined
Bilateral
LEGAL EMPLOYMENT commissions/
Education , agreements
Academic centers SYSTEMS, Policy FORCE/
of excellence & makers, Government
other Research International Institutions
institutions conventions, Insurance Levy,
Regional Businesses &
strategies Industry

31. Etiological factors behind cancer of the
Cervix .Hormonal contraceptives
• women -Early coitus /preparations like depo
[Stern et al 1977]
• Multiparious women
• STI’s- infection, etc.
• Multisexual partners
• Viral HIV,
• It varies with race [genetic 81% ?
susceptibility ,etc] • Viral HPV,
• High in low socio-economic stata • Viral H Herpes
•
[malnutrition,poor health facilities] Smoking [TARR/hetero]
• Poor hygiene[smegma factor] • Alcohol drinking
• Sperm factor[acridine histones] • Drugs (Diethylstilbestrol-
• Women with boyfriends with CA. DES),cyclophosphamide
penis • Pelvic irradiation.
• History of cancer from other
sites e.g uterus, colon.

32. 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

34. Disease Burden
HPV types 6, 11, 16, & 18
HPV Type Approximate Disease Burden
 70% of cervical cancer, AIS, CIN 3,
16 and 18 VIN 2/3, and VaIN 2/3 cases
 50% of CIN 2 cases
 35%–50% of all CIN 1, VIN 1,
6, 11, 16, and 18 and VaIN 1 cases
 90% of genital warts cases

35. GARDASIL® (Quadrivalent Human Papillomavirus [HPV Types 6, 11, 16, 18] Recombinant Vaccine)
Classification of Histological Findings
CIN 1 CIN 2
CIN 1 (mild (moderate CIN 3 Invasive
CIN1 Normal (condyloma) dysplasia) dysplasia) (severe dysplasia/CIS) 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.

36. 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

38. HPV-DNA FISH

42. GARDASIL® (Quadrivalent Human Papillomavirus [HPV Types 6, 11, 16, 18] Recombinant Vaccine)
Cervical Transformation Zone
• 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

43. 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.

44. GARDASIL® (Quadrivalent Human Papillomavirus [HPV Types 6, 11, 16, 18] Recombinant Vaccine)
Cervical Intraepithelial Neoplasia-
VIAM
CIN 1 CIN 2 CIN 3
VIA-

45. GARDASIL® (Quadrivalent Human Papillomavirus [HPV Types 6, 11, 16, 18] Recombinant Vaccine)
Invasive Cervical Carcinoma
From IARC, 2003.1

46. 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

48. HPV-Related Disease Development

49. HPV Type Prevalence Worldwide
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.

50. 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.

51. 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

52. 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.

53. Clinical Trials
• FUTURE I & FUTURE II studies
• Phase III, prospective, double-blind, placebo
controlled trials in 29 countries
• Females ages 15 - 26

54. GARDASIL® [Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine]
GARDASIL Is Efficacious Against HPV 16– and
18–Related CIN 2/3 or AIS
GARDASIL Placebo
60
53
50
40 n=8,460
Related Cases
30
100%
20 Efficacy
10
n=8,487
0
0
CIN 2/3 or AIS
 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.
CIN = cervical intraepithelial neoplasia; AIS = adenocarcinoma in situ. 54

55. GARDASIL® [Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine]
GARDASIL Is Efficacious Against
HPV 6/11/16/18–Related VIN and VaIN
GARDASIL Placebo
12
10
10
8
Related Cases
n=7,741
6
100%
4 Efficacy
2
n=7,769
0
0
VIN 2/3 or VaIN 2/3
 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
VIN = vulvar intraepithelial neoplasia; VaIN = vaginal intraepithelial neoplasia.
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. 55

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. 56

57. Genital & Anal warts
57

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.
58

59. Cervical Cancer and HIV
 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
59

60. GARDASIL® [Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine]
GARDASIL Is Efficacious Against
HPV 6/11/16/18–Related Lesions
GARDASIL Placebo
100
91
90 83
80
70
60 n=7,861 n=7,899
Related Cases
50
95% 99%
40 Efficacy Efficacy
30
20 n=7,858 n=7,897
10 4
1
0
CIN 1, CIN 2/3 or AIS Genital Warts
 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
CIN = cervical intraepithelial neoplasia; AIS = adenocarcinoma in situ. 60

62. 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

63. EPI Information and Data Flow

65. • THANK YOU FOR LISTENING