PREVENTION OF CERVICAL CANCER

PREVENTION OF CERVICAL CANCERDR EMAGBETERE O .A (MBBS, FMCOG, FWACS)PRETEST Answer true or falseCervical cancer is a sexually transmitted disease.Lack of basic health education is a serious contributor to cancer of cervix(ca cervix) occurrence.Health practitioners and government contribute to high incidence of ca cervix in Nigeria.About 25% of women will be infected with Human pappiloma virus at some point in their livesVaccination alone is the only effective way of preventing ca cervix.Cervarix is a highly effective vaccine against HPV 11, 16 and 18

2OUTLINEIntroductionCauses of cancer increaseCervical screeningPreventionHuman papilloma virusHPV vaccinesCAPITOL HILL CCLINIC/HOSPITALIntroduction Disease of inequitySecond most common cancer among women worldwide, with about 493,000 new cases diagnosed annually. 274,000 deaths due to cervical cancer each year.>80% occur in developing countries.Expected to increase to 90% by 2020(1).It is the largest single cause of years of life lost to cancer in the developing world(2) (1)Parkin DM, Bray F. Chapter 2: the burden of HPV-related cancers. Vaccine 2006;24:Suppl 3:S11-S25 (2) Agosti JM, Goldie SJ. Introducing HPV Vaccine in Developing Countries Key Challenges and Issues NEJM 2007;356:1908-1910 SOGON 2007 BENIN CITY

CAPITOL HILL CLINIC/HOSPITAL Global Cervical Cancer Incidence

6Globally, the highest mortality rates for cervical cancer occur in africa, central and south america and parts of south central and south eastern asiaSOGON 2007 BENIN CITYComparison of Mortality due toCancer vs. Infectious Diseases

SOGON 2007 BENIN CITYProjected Evolution of Cancer Cases

REASONS FOR CANCER INCREASE IMMUNOSUPPRESIONAssociated with the persistent of HPV infection & may hasten the journey to carcinoma in-situHIV/AIDS pandemic in AfricaPoverty Many live on < 1$ a day!Sexual networking (?) effects from other STIsSchiffman et al 2007 Lancet,370:890 907Chama et al 2005, J Obstet Gynecol 25(3):p286-8.CAPITOL HILL CLINIC/HOSPITALCAPITOL HILL CLINIC/HOSPITALLack of political will/CommitmentWomen are dying not just because we do not understand the cause but we have not consider their lives worth savingMahamud Fathalla Former FIGO president

Many African Leaders of head of states do not have concrete plans for genital cancer screening e.g. Nigeria has no national programme in place not to mention the poorer and war torn countries!

POOR HEALTH SEEKING BEHAVIOURBelief that health institution needs to be visited only when one is sick negates screening opportunities.Women in our continent typically do not receive care until their disease is well advanced, it is usually fatalVisit at least a native practitionerApathy of Men to womens health issues. Lack of economic empowerment of women.80% present late

CAPITOL HILL CLINIC/HOSPITALCAPITOL HILL CLINIC/HOSPITALLack of Awareness and Knowledge women lack basic health educationSome women do not know the importance of a pap smear test, find them embarrassing or even traumatic, and in part this may explain why screening fails to reach everyone who is at riskHealth practitioners underestimate level of risk CAPITOL HILL CLINIC/HOSPITALWeak Health Systemslittle existing public health infrastructureA 2001 study by the World Health Organization found no organized cervical cancer screening programs in many Latin American countries, any of the high-risk Sub-Saharan African countries or IndiaCAPITOL HILL CLINIC/HOSPITAL PovertyPap smears are expensive, costing about (US$9) each, and any abnormality detected requires referrals and follow-up which, according to Prof Helen Rees, executive director of the Reproductive Health and HIV Research Unit at the University of Witwatersrand, "don't always happen when services are overstretched CAPITOL HILL CLINIC/HOSPITALPoverty Index: % Living below Poverty Line.CountryPercentageNigeria70.8Ghana44.8Zambia75.8South Africa10.7Rwanda51.7Tunisia< 2.0CAPITOL HILL CLINIC/HOSPITALCervical Cancer:A Failure of Screening !Failure to be screened: 50 60 %EverAt an appropriate intervalFailure of screening: 40 50%Screening did not show an abnormalityFalse negativeInterpretation errorSmear takers errorFailure to follow up on recommendations of screening program: 10 20 %

CAPITOL HILL CLINIC/HOSPITALWHY IS IT PREVENTABLE ? Sexually transmitted malignancy: HPV 16, 18 & others

Window of opportunities.Premalignant latency period.Comparatively slow growing.Screening extremely cost effective.Cure of premalignant lesion realizable

Availability of the vaccine

CAPITOL HILL CLINIC/HOSPITAL PREVENTIONSPrimary PreventionRisk reductionCondom useCircumcisionVaccineSecondary PreventionScreeningCAPITOL HILL CLINIC/HOSPITALPRIMARY PREVENTIONOBSTACLESDifficult to change behaviourCultural practicesCostlyPoliticalReligiousLack of awarenessCAPITOL HILL CLINIC/HOSPITALSECONDARY PREVENTIONMethods of screeningPap smearHPV DNA testingLiquid cytology/Thin prepVisual inspection of cervix using acetic acidVILIMVIACervicogramsPolarprobeOptical Technologies

CAPITOL HILL CLINIC/HOSPITALSECONDARY PREVENTIONDrawbacksCostNeed for specialized skilled personnelNeed for functional laboratoriesFollow-up schedulesLack of resourcesSensitivity/SpecificityCAPITOL HILL CLINIC/HOSPITALWhat does a Pap smear test involve?vaginal speculum exam during which a sample of cells from a womans cervix using a small flat spatula or brush.Smearing and fixing cells onto a glass slide.Sending the slide to a cytology laboratory where it is stained and examined under a microscope to determine cell classification.Transmitting the results back to the provider and then to the woman.

22Slide overview: The Pap test involves a number of steps that have to be done with the appropriate lab technology.CAPITOL HILL CLINIC/HOSPITAL

Spatula-CytoBrushTransfered on the slide(Fixation)

Papanicolaoustaining

Pathology Review Specimen Preparation for Clinical CytoPathology (Pap Smears)CAPITOL HILL CLINIC/HOSPITALStrengths of cytology:Historical success in developed countries.High specificity, meaning women with no cervical abnormalities are correctly identified by the test with normal test results.A well characterized screening approach.May have the potential to be cost-effective in middle-income countries.24Slide overview: There are many strengths to cytology, including its tremendous contribution to reducing cervical cancer incidence and mortality rates in developed countries.

Note for bullet 1: When the Pap test was introduced in the 1940s, it was the only cervical screening test to date worldwide. Cervical cancer incidence and mortality rates have decreased in developed countries where the Pap test is used as part of well-organized screening and treatment programs. Note for bullet 3: Well characterized means that the Pap smear technique and the test qualities have been well studied and described.Note for bullet 4: Middle-income countries tend to have more substantial infrastructural, technical, and clinical capacities that can support the provision of effective cytology services.CAPITOL HILL CLINIC/ HOSPITALLimitations of cytology:Moderate to low sensitivity:High rate of false-negative test resultsWomen must be screened frequentlyRater dependentRequires complex infrastructureResults are not immediately availableRequires multiple visitsLikely to be less accurate among post-menopausal women

25Slide overview: The Pap test also has imperfections which limit its effectiveness, particularly in low-resource settings.

Note for bullet 1: As defined earlier, sensitivity is the proportion of individuals with disease who are correctly identified by the test as having disease. A test with low sensitivity means that women with disease will be falsely identified as being free of disease. As many lesions go undetected, program impact is limited unless women are screened frequently. Frequent screening can be difficult in low-resource settings. Note for Bullet 2: Rater dependent means the test's performance depends on the abilities of the person doing the test (versus a machine, as for HPV testing). This means that even when service providers have training, test performance may vary depending on service delivery conditions and other factors. Note for bullet 3: Few low-resource countries have the resources to provide frequent and effective screening.Note for bullet 5: The fact that the Pap test requires multiple visits can lead to a great deal of loss to follow-up in many low-resource settings. Between screening, getting the results analyzed, getting a woman back in for the results, and getting her treated if confirmed abnormal, programs often are not able to follow up with women. It is noteworthy here that there is also loss to follow-up in developed countries.

CAPITOL HILL CLINIC/HOSPITALAssessment Newer TechnologiesFluorescence and reflectance spectroscopy for real-time screening and diagnosisQuantitative cytology for objective, real-time screening (Hybrid Capture, HPV DNA, mRNA)Quantitative histo-pathology to relate optical measurements to a quantitative model of progressionConfocal Microscopy and In Vivo Confocal EndocopyVisual Inspection( ACA/LI) CAPITOL HILL CLINIC/HOSPITALNew version of the CytoSavant : works with H@E stained specimen

CAPITOL HILL CLINIC/HOSPITALSpecimen Preparation for Quantitative Cytology (Thin-Prep)

Feulgen-Thionin Staining

PreservCyt solution

ThinPrep Processor CytoSavant Automatic Scanning Spatula-CytoBrushCAPITOL HILL CLINIC/HOSPITALMulti-spectral digital colposcopyMulti-spectral digital colposcopy is a technology unlike the probe in that the device has no contact with tissue and takes an image of the entire cervix. The device consists of white, green, and blue light. The green light fluoresces blue and the blue light fluoresces green. CAPITOL HILL CLINIC/HOSPITALFluorescence SpectroscopyFluorescence and reflectance spectroscopy have been shown to differentiate precancerous and normal tissues. Using a point probe that interrogates a 2mm area, it has demonstrated increased sensitivities and specificities respectively. A diagnostic trial in which all measured sites were biopsied reveals a sensitivity and specificity of 80% and 70% using a variety of algorithmic approaches

SOGON 2007 BENIN CITYPatient 5

CAPITOL HILL CLINIC/HOSPITAL

Patient 9CAPITOL HILL CLINIC/HOSPITALHuman Papilloma VirusThe Necessary Cause AboundsGenital HPV is an extremely common viral infection. (Of the more than 100 known HPV strains, 30 are sexually transmissible and are considered genital HPV.) Up to 80% of women will be infected with HPV at some point during their livesThe vast majority of cases are transient: The body's immune system fights off the infection, which then either becomes inactive or resolves on its own. Why does it persist in some individuals?

Smith et al. UnpublishedFive Most Common HPV Types in Invasive Cervical Cancer by Region%HPV TypeAll Cases

%HPV TypeAsia

%HPV TypeNorth American and Australia

%HPV TypeAfrica

%HPV TypeEurope

%HPV TypeSouth and Central America71.8%73.8%65.1%75.8%66.9%70.4%34CAPITOL HILL CLINIC/HOSPITALHPV: a challenge for the immune systemHPV is designed to evade the natural immune defense mechanisms:No viraemiaHPV does not kill keratinocytes:no inflammationno pro-inflammatory cytokinespoor activation of epithelial APCs

35CAPITOL HILL CLINIC/HOSPITAL

Natural History of HPV Infection:Surrogate Markers for Cervical Cancer0 to 5 YearsUp to 20 YearsInitialHPV InfectionCIN 1Cleared HPV InfectionSq. Cell CarcinomaCIN 2PersistentInfectionCIN 3Adeno- CarcinomaAISBasis for Licensure/Cancer Efficacy:

Demonstrate Prevention of HPV 16/18-CIN 2/3 + AIS37CAPITOL HILL CLINIC/HOSPITALHPV Vaccine DevelopmentL1L1L1 Creation of virus-like particles (1991) Mimic natural virion structureGenerate potent immune response Contain no DNA**Non-infectious**Cannot cause disease38Came in In 1991, when Zhou et al successfully created virus like particles based on the known HPV structure.These particles, known as VLPs, mimic the natural virion structure, and thus generate a potent immune response. They contain no DNA, however, and are thus non-infectious.

15 years of work later finally led to FDA approval of Gardasil..SOGON 2007 BENIN CITY

CAPITAL HILL CLINIC/HOSPITALGARDASIL in SummaryGARDASIL is well-tolerated and safeGARDASIL is highly effective at prevention of:Persistent infection with HPV types 6/11/16/18Clinical disease caused by HPV types 6/11/16/18Protection appears to be durable, with stable antibody levels for at least 3.5 years post immunizationGARDASIL is a prophylactic vaccine and does not treat disease or infection with HPVGARDASIL does not replace screening

**Studies conducted in >27,000 subjects in 33 countriesCAPITOL HILL CLINIC/HOSPITALCC is a critical public health problemGSK cervical cancer vaccine (Cervarix) is highly protective against HPV-16/18 CIN2+ in a broad population of women aged 15-25 years.GSK cervical cancer vaccine (Cervarix) is very immunogenic in women aged 10-25 years.GSK cervical cancer vaccine (Cervarix) is generally safe and well tolerated in the current clinical program, with pain at injection site being the most frequently reported symptom.CAPITOL HILL CLINIC/HOSPITALMaking Cervical Cancer HistoryEffective collaboration predicated on shared vision, trust and commitment to advocacy for global cervical cancer controlFunding to support vaccination and screening programs Research to guide optimal implementation strategiesRealistic efforts by all partners to share or mitigate risk Achievement of, and action on, common vision of optimal product profiles, vaccine demand forecasts and sustainable introduction strategies

Public health partners need to pursue a highly collaborative program of global HPV vaccination and screening to limit the impact of the second leading cause of cancer in women worldwidea cancer that should now be largely preventable BE SCREENED TODAYBE VACCINATED TODAYPOST TEST Answer true or falseCervical cancer is a sexually transmitted disease.Lack of basic health education is a serious contributor to ca cervix occurrence.Health practitioners and government contribute to high incidence of ca cervix in Nigeria.About 25% of women will be infected with Human pappiloma virus at some point in their livesVaccination alone is the only effective way of preventing ca cervix.Cervarix is a highly effective vaccine against HPV 11, 16 and 18

Chart49922674227133709751524297619

CountryNew CasesNew Cases - 2002 - Selected African Countries

Sheet1World493,243MDC83,437LDC409,404East Africa33,903Middle Africa8,201North Africa8,175South Africa7,698West Africa20,919Nigeria9,922RSA6,742Egypt2,713Congo3,709Tanzania7,515Uganda2,429Ethiopia7,619

Sheet100000000

CountryFigureGlobacom 2002 Incidence of Ca Cx

Sheet20000000

CountryFigureNew Cases - 2002

Sheet3