CERVICAL CANCER BURDEN IN SOUTHERN AFRICA AND LESOTHO

Sejojo Phaaroe M.T ; C.T( I.A.C) ; M.I.B.M.S (U.K ) ; Cert. Assessor, (SANAS/SADCAS-SQAM/EU),Registered EU Health NCP ( FP7 and Horizon 2020) ,

thinktankentr@gmail.co.za

•Twitter•LinkedIn•Google+

Principal Bio medical Scientist –cytopathology Cytotechnologist of the International Academy of cytologists #6467

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

Our Plan for Today Importance of cervical cancer around the world and

in Lesotho (Comprehensive review of international conventions on RH cancers )

Etiological factors behind cancer of the Cervix Signs and symptoms/ clinical presentation Lesotho Disease Burden

HPV and the disease progression - New option for primary prevention- and vaccination

Prevention Strategies ( comprehensive cervical cancer screening and prevention)

Gardasil vaccination Integration into EPI program

Comprehensive review of international conventions on RH cancers – and Comprehensive Cervical Cancer Prevention • IUAC ( International union Against Cancer)

• IUCR ( International Union on Cancer Research )

• IAC (International Academy of Cytology)

• WHO (2002) - • AFROX declaration (2007)

• Ouagadougou Regional Consultation on Cervical Cancer Recommendations (2008) for WHO Member States

• …AU ( Maputo SRH declaration)

• . SADC-

• …Lesotho Road map ( Maternal Mortality SRHR)

WHO, 2002

1- WHO- National Cancer Control Program2002 2. Lesotho RH Cancer Screening Guidelines, HPV vaccination guidelines 3. LBCN President was instrumental in building the Guidelines for Lesotho.

4. APCA- advocacy for Palliative care in Africa –Cancer Advocacy Lead Champion- Lesotho Country Team

5. Report of an African Regional Meeting on Cervical Cancer – Uganda September 2010

6. Institute of Health systems & Programs-Technical Advisory Committee on cancer coalition - SADAC/UNAIDS – June 2013

WHO, 2002

Lobbying for Support from African Policymakers and Parliamentarians: The Uganda Experience

Honorable Sarah Nyombi

Member of Parliament, Uganda

YES WE CAN!!!!!

Introduction • Research into health problems in developing countries

has traditionally focused on infectious and nutritional diseases especially in children.

• Lately attention was focal at HIV /TB and AIDS issues alone

• Now there is emergence of XDR, and MDR-TB• An assumption often made is that chronic diseases, especially

cancer are rare diseases which affect only the older segment of our community

• This assumption is wrong• Cancer mortality in adult is 15-84 , and HIV EPIDEMIC LEAD TO

RISE IN VIRUS RELALATED CANCERS SUCH AS CANCER OF THE CERVIX -Hughes-Davies & Spittle 1991

• Cervical cancer is both preventable and curable,• provided it is detected at an early stage. • In developed countries 80% of cervical cancer cases

detected are cured because of early detection. • However, in developing countries 80% of cervical

cancer cases are incurable at the time of detection, if they are detected at all.

• (Bulletin of the World Health Organization, 1996, 74 (4): 345-351)

Global burden on cervical cancer• ½ million women die of cervical cancer world wide/ yr• Cervical cancer is the most common cancer in Lesotho ¹ • with a high pick up age 40-49 ¹ and the leading cause of death from

cancer amongst women in sub Saharan Africa.²• Cervical cancer screening programs have reduced the incidence of

cancer of the cervix• because cervical cancer generally develops slowly and has a readily

detectable and treatable precursor condition [severe dysplasia / Carcinoma insitu (CIS)] – By Cytology

• It can be prevented through screening and treatment of at risk women.

• Through vaccination of young population for high risk HPV viruses which cause CXCA

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 epithelial tissue covering the lining of the neck of the womb in women

• 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 ( see later)

Developed Developed Countries: Countries: 80,002 cases80,002 cases

Leading cause of Leading cause of cancer death for cancer death for women in women in developing developing countriescountries

83% in developing 83% in developing countries countries -- who have only -- who have only 5% of cancer care 5% of cancer care resourcesresources

Developing CountriesDeveloping Countries390,598 cases390,598 cases

Denny, BJOG, 2005

Magnitude of the Problem

Distribution Of Common Cancer Between the Sexes

Males Lung Prostate Stomach Liver Colorectal Oesophagus

Females Cervical Breast Lung Stomach Colorectal

S.Phaaroe et al

S. Phaaroe etal

Estimated number of adults and children newly infected with HIV, 2007

Western & Central Europe

31 00031 000[19 000 – 86 000][19 000 – 86 000]

Middle East & North Africa

35 00035 000[16 000 – 65 000][16 000 – 65 000]

Sub-Saharan Africa

1.7 million1.7 million[1.4 – 2.4 million][1.4 – 2.4 million]

Eastern Europe & Central Asia

150 000 150 000 [70 000 – 290 000][70 000 – 290 000]

South & South-East Asia

340 000340 000[180 000 – 740 000][180 000 – 740 000]Oceania

14 00014 000[11 000 – 26 000][11 000 – 26 000]

North America

46 000[38 000 – 68 000]

Latin America

100 000100 000[47 000 – 220 000][47 000 – 220 000]

East Asia

92 00092 000[21 000 – 220 000][21 000 – 220 000]Caribbean

17 000[15 000 – 23 000]

Total: 2.5 (1.8 – 4.1) million

Why the shift?

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

• Area of metaplasia at Area of metaplasia at squamocolumnar junctionsquamocolumnar junction

• ~99% of HPV-related ~99% of HPV-related genital cancers arise within genital cancers arise within the transformation zone.the transformation zone.

• The Pap test obtains cells The Pap test obtains cells from the transformation from the transformation zone for cytology zone for cytology screening.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

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% ?

Do we know what causes cervical cancer?

Yes There is a paradigm shiftIn Medical Science and Laboratory Medicine

Human Papilloma Virus (HPV) and Cervical Cancer

1008 cervical cancer specimens 32 hospitals in 22 countries HPV DNA detected in 99.7% of specimens Over 20 different subtypes identified HPV 16 and/or 18 present in 64%

Bosch FX et al. J Natl Cancer Inst 87:796, 1995Walboomers JMM et al J Pathol 189:12-19,1999

Morphogenesis of squamous dysplasia & Invasive squamous cell carcinoma

• Ectocervical Endocervical mucosa

reserve cell hyperplasia • Dysplasia squamous metaplasia small cell CA O

• Infiltating large cell CA O ?

• INFILTRATION INFILTATION

• Keratinizing SQCA Non-Kerat Sq Ca small cell sqca

Cytological Manifestation of Dysplasia• Involve • the Ectocervix• Portio/ transformation zone• Endocervix• Number of abnormal cells

• Varies with site and size of the lesion

• Varies with the method of making the smear

• Cytologists judge the severity of a dysplasia on the degree of morphological atypia, N/C ratio, and Medical intelligence 0

50

100

150

200

250

300

mild

no;# ofcells onsmears<300microinvasion<320cancer

Subclassification of cases of Dysplasia and Cancer of the cervix

-distribution of 2180 cases -( S.Phaaroe et al 2004 )

0

200

400

600

800

1000

1200

1400

1600

1800

Slight moderate severe total

keratinisingnon-keratmetaplastic

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.)

• The Cytologist should expect micro-biopsies or an inadequate smear scraping because of blood

• The Clinician should blot the blood with 5%CH3COOH

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

Clinical Staging of CACX• Precancer: Dysplasia- a degree of epithelial abnormality

occurs when normal cells undergo bad changes but too early to be called malignant, however if the condition is left untreated will progress to cancer. CIN 1, 2, and CIN3

• There is no agreement over the progression rate• Stage CA CX 1.O = CAO= CIN3/CAO= confined to surface

epithelium• CACX stage 1.A= Less or equal < 5mm invasive beyond

stroma= micro-invasive CACX• CACX stage 1.B= > 5mm invasive beyond stroma• Stage CACX 2. A = Spread beyond CX• CACX 2.B =Early para-metrium invasion

Stage CACX 3

• More Extensive spread• CACX 3.A = Involves lower third of vagina• CACX 3.B= Parametrium and pelvic side wall

metastasis

• STAGE CACX 4• Extension to bladder• Rectum• True pelvis• Distant organs

viruses causing HIV/AIDS defining cancers

HERPES & K.S

EPSTEIN B Virus Non Hodgkin's Lymphoma

Human Papiloma virus

Cervical, Anal, ConJunctival squamous cancers, Germ cell tumours

HIV & CMV Cervical, Anal, Conjnctival squamous cancers, Germ cell tumours

HIV Clinical stages at different CD + counts (1993 CDC) CD 4+ COUNT INFECTIONS NEOPLASIA/

CANCERS >500 cells/ ml CANDIDIASIS

CERVICITIES CIN Invasive Cancer of cervix Idiopathic Thrombocytopenia purpura Hodkins Lymphoma Non Hogkins Lymphoma K.S

200-500 TB , Bacterial pneumonia Herpes Zoster Oral candidiasis Oesophagial candidiasis

CIN Invasive Cancer of cervix Idiopathic Thrombocytopenia purpura Hodkins Lymphoma Non Hogkins Lymphoma K.S

50- 200 Extra pulmonary TB PCP Cryptococoosis Toxoplasmosis Blastomycetes Septicaemia Herpes

Wasting- Anaemia Peripheral Neuropathy Non Hodgkins Lymphoma Cardiomyopathy

<50 CMV

Human Papilloma Virus (HPV)

• Double-stranded DNA virus• More than 100 different types• Sexually transmitted

• “Low-risk” types (6, 11, 42, 43, 44) are associated with genital warts

• “High-risk” types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58) are associated with cervical cancers

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.

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

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

Desktop Baseline study of CACX 2007 • 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

Lesotho Disease Burden Leribe and Mohale’s Hoek Referrals*

1 Jan 2005 – 31 March 2006 Retrospective analysis of cytology

and histology archives Age Standardized Incidence Rate

66.7:100,000 women*Phaaroe, 2007

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

cont• Total cost of treatment was crude estimated to M 10, 692 000.00 Million for already histological

confirmed cervical cancer in a period• Cytological Intervention could have been done

earlier in the women ‘s lives (10 yrs) had the right criteria for screening been used-

• All invasive cases SHOULD HAVE been / have been referred to South African hospital for treatment at a standard cost of R108 000 per patient course of treatment until the patient is cancer free. (This fee was R35 000 in 1995, WHO Report)

• What is the Cost Now ??????????

• CYTOLOGY COST REDUCTION INTERVENTION =M 17 064 000, 00 m in the stipulated

period ( 1 year.3months)• This depends upon if all patients

HAVE been well recalled/followed up using SOP’s and treated Modalities in the Guidelines when intervention is still possible

Cervical cancer is highly preventable with both Primary and Secondary

Prevention

Prevention Strategies

So What do we do? Pap smears and HPV testing has to be capacitated in

Lesotho There is a strong relationship between HPV, HIV and

cervical cancer progression rate Direct Visual Inspection (DVI) with immediate treatment

can reduce cervical cancer by about 37% in a single visit, BUT requires quality control, competency, QMS and is provider dependent .

Over diagnosis possible- (ethico-Legal issues) Immunization against HPV is now feasible and can

reduce cervical cancer by about 70%!

WHO- Public Health

(Stjernsward, 2007)

Oncology ?

problem

Lab tests?

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

Training health professionals cervical cancer prevention guidelines and HPVV

Global Progress in HPV vaccine introduction

Global Progress in Visual Inspection (VIA) for Cervical Cancer Screening

Global Progress in HPV DNA testing

Screening for cervical cancerScreening for cervical cancer

Dr. George N. Papanicolaou, who devised the "Pap" smear test for cancer, Dr. George N. Papanicolaou, who devised the "Pap" smear test for cancer, examines a slide in his laboratory in 1958.examines a slide in his laboratory in 1958. NOVA, PBSNOVA, PBS

What does the pap test do? Detects pre-invasive disease which

can then be treated

Finds early cancer with better prognosis

Highly sensitive in picking up High risk CACX related / causing infections – HPV, Herpes, etc

How is it done?

Mortality Rate Cervical CancerMortality Rate Cervical CancerUS, 1950-presentUS, 1950-present

0.0

5.0

10.0

15.0

20.0

1950 1955 1960 1965 1970 1975 1980 1985 1990 1995

US

ASR , age 20+ (per 100,000)ASR , age 20+ (per 100,000)

US 50% pap US 50% pap coveragecoverage

World Health Organization Databank, November 2001

US 80% pap US 80% pap coveragecoverage

G3 G2 G1

RED MIX BLUE/GREEN

chromogenic in situ hybridization• CISH, or chromogenic in situ hybridization, is a process in which a

labeled complementary DNA or RNA strand is used to localize a specific DNA or RNA sequence in a tissue specimen.

• CISH is used to evaluate gene amplification, gene deletion, chromosome translocation, and chromosome number.

• CISH utilizes conventional peroxidase or alkaline phosphatase reactions visualized under a standard bright-field microscope, and is applicable to formalin-fixed, paraffin-embedded (FFPE) tissues, FNAB , blood or bone marrow smears, metaphase chromosome spreads, and fixed cells. CISH offers:

Evaluation of gene status simultaneously with tissue morphology ■Use of existing bright-field microscopy and techniques similar to FISH ■Archivable and quantitative results■

RED BLUE

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

Appearance of the Normal Cervixon 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.

Visual Inspection Identifies Early Cancer Related to HPV

NegativeNegative PositivePositive

Photo source: JHPIEGOVIA : - / + acidowhite lessions

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

Cervical Intraepithelial Neoplasia- VIAM

CIN 1 CIN 2 CIN 3

VIA-

Direct Visual Inspection:Lugol’s Iodine- VILI

Photo source: IARC

NEGATIVENEGATIVE POSITIVEPOSITIVE

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

Invasive Cervical Carcinoma

From IARC, 2003.1

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

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.

HPV Types 6, 11, 16, 18 in Cervical Cancer and Genital Warts

0

10

20

30

4050

60

70

80

90

100

LSIL HSIL Cervical cancer Genital warts

HPV 16 and 18 HPV 6 and 11

Pre

vale

nce

of H

PV

T

ype

30%30%50%50%

70%70%

90%90%

Are HPV Types 16 and 18 common in southern Africa?

High prevalence of HPV 16 in South Africa

Cervical cancer biopsies 82% contained type 16 and 10% type 18.

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.

MOLECULAR ANATOMY OF HPV

• HPV consists of a double-stranded circular DNA genome, containing 7800–7900 base pairs,

• a non-enveloped virion and an icosahedral capsid. • The genome is organized into three regions,• the upstream regulatory region (URR, non-coding)• and the early gene regions (EGR)• late gene regions (protein encodeing). LGR

URR

ERR

LRRE1-E7

Schematic drawing

by Sejojo PhaaroeHPV-DNA

Molecular structure of HPV

cont• These encode all the viral proteins except

for the viral capsid proteins, which are encoded in the late region..

• The E6 and E7 proteins are of specific importance in cancer.

• In fact, recent studies have shown that the oncogenic potential of the high-risk HPV genotypes depend on E6 and E7 expression.

HPV AND CELL INTRERACTION• The importance of HPV E6 in cancer appears to be

because of its effects on the epithelial cellular tumor suppressor gene, p53.

• Alterations in the p53 gene, including deletion, insertion and point mutation are the most frequent genetic events in many different carcinomas,

• such as in colon, breast skin , cervix and lung]. • The p53 gene negatively regulates cell cycle and

requires ‘‘loss of function’’ mutations for tumor formation

• The normal function of p53 includes transient increase in expression after DNA damage occurs, leading to cell cycle arrest in the G1 phase.

• This arrest allows for repair of the DNA,or if repair is not possible, cells will undergo an apoptotic death.

• p53 acts through downstream regulators, such as p21,leading to inhibition of cyclin-dependent kinases, and eventually blocks Retinoblasoma (RB) gene phosphorylation pre-venting cell cycle progression

• It can lead to apoptosis through changes in levels of BAX and BCL-2 family members expression

                                                                                        

The Cell Cycle

The checkpoints are surveillance mechanism and quality control of the genome to maintain genomic integrity. Checkpoint failure often causes

mutations and genomic arrangements resulting in genetic instability.

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

risk

• Some Adenoviruses , HIV and, HPV E6 protein all can form a complex with and inactivate p53.

• E6 also stimulates p53 degradation through a selective ubiquitin-dependent proteolytic pathway( cascade reaction)

• The E6 proteins of high oncogenic risk types of HPV have higher affinity for p53 compared with the low-oncogenic risk types

Advanced infection

• The rate of HIV production determines the amount of virus in the blood and this in turn, determines the rate of CD4+ cell destruction

• HIV accumulation eventually results in the destruction of lymph node architecture , the immune system –Military force and the release of virus and other previously trapped contents[fungi, TB, bacteria] into circulation

OPI’s - Entamoeba histolytica-

                                                             Trophozoite of E.histolytica

forma minuta. 10-20 µm in diameter.

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!

Risk of Cervical Lesions and Cancer in Risk of Cervical Lesions and Cancer in Women Exposed to HPV at a Young AgeWomen Exposed to HPV at a Young Age11

0

1

2

3

4

5

6

7

CIN Invasive Cervical Cancer

Re

lati

ve

Ris

k E

sti

ma

tes

*

≥23 or Never

18–22

≤17

*Mantle-Haenszel estimates adjusted for age only1. La Vecchia C, Franceschi S, DeCarli A, et al. Cancer. 1986;58:935–941.

Relative risks for CIN and invasive cancer increase with decreasing age of first sexual intercourse

Age at First Intercourse (Years)

(n=206) (n=327)

Prevention: GARDASIL“Merck to Donate Three Million Doses of Gardasil, its Cervical Cancer

Vaccine, to Support Vaccination Programs in Lowest Income Nations” - Sept. 26, 2007

1 million females over 5 years

- Criteria included justification of evidence of magnitude of the problem, and intervention strategies

- Lesotho had the baseline study and tools in place - I am blessed and proud to have been a Lead in this Lesotho study , Thanks to funding from WHO.

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

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]

Intramuscular administration

Each 0.5ml dose contains approximately 20 mcg of HPV 6 L1 protein, 40 mcg of HPV 11 L1 protein, 40 mcg of HPV of 16 L1 protein and 20 mcg of HPV 18 L1 protein.

Each 0.5ml dose of vaccine contains 225mcg of aluminum hydroxyphosphate sulfate adjuvant 9.56 mg of sodium chloride, 0.78 mg of L-histidine, 50 mcg of polysorbate 80, 35 mcg of sodium borate, and water for injection.

This product doesn’t not contain a preservative or antibioticsAfter agitation, Gardasil is white, cloudy liquid. Injection will be intramuscular in the right hand or upper

anterior right thigh over 6 months period. First dose at elected date, second dose two months from the

first dose and the third dose is after the six months of the first dose

Mechanism of action • L1 VLP vaccines is mediated by the

development of humoral immune responses to Gardasil (quadrivalent human papillomavirus type 6,11,16,18 recombinant vaccine)

• Gardasil is designed to prevent HPV 6,11,16,18 related cervical cancer, cervical dysplasias.

• Gardasil is a prophylactic vaccine

• Gardasil doesn’t prevent infection with the HPV types not contained in the vaccine.

EPI Information and Data Flow

100

Organization Personnel Equipment

Purchasing & Inventory

Process Control

Information Management

Documents& Records

Occurrence Management Assessment

Process Improvement

Customer Service

Facilities & Safety

The cervical cancer Quality Management Systems

Making a Case for Cervical cancer M&E

The Legs (Programme Implementers):

Coordinate Implement of projects, spend the budget, report on results and leave footprints of the organisation in the community.

The Arms and Spine (M&E Champions):

Standard bearers of M&E Values and principles, concepts, methods, tools

.Head (Senior Management):Think Tank (Lesotho breast cancer network, The Org Brain Machine)Sets the Agenda. Eye, Nose, and Ears and Mouth of the Org, break the silence

Impact assessment

Sejojo Phaaroe 2009

Road is clear now , only remove some few misconceptions and myths obstructing the way

• THANK YOU FOR LISTENING