PREVENTION OF CERVICAL CANCER

1. PREVENTION OF CERVICAL CANCER DR EMAGBETERE O .A (MBBS, FMCOG, FWACS)

2. PRETEST Answer true or false • Cervical 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 lives • Vaccination alone is the only effective way of preventing ca cervix. • Cervarix is a highly effective vaccine against HPV 11, 16 and 18

3. OUTLINE • Introduction • Causes of cancer increase • Cervical screening • Prevention • Human papilloma virus • HPV vaccines

4. Introduction • Disease of inequity • Second 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 IssuesNEJM 2007;356:1908-1910 CAPITOL HILL CCLINIC/HOSPITAL

5. SOGON 2007 BENIN CITY

6. Global Cervical Cancer Incidence CAPITOL HILL CLINIC/HOSPITAL

7. Comparison of Mortality due toCancer vs. Infectious Diseases SOGON 2007 BENIN CITY

8. Projected Evolution of Cancer Cases SOGON 2007 BENIN CITY

9. REASONS FOR CANCER INCREASE IMMUNOSUPPRESION Associated with the persistent of HPV infection & may hasten the journey to carcinoma in-situ • HIV/AIDS pandemic in Africa • Poverty – Many live on < 1$ a day! • Sexual networking (?) – effects from other STIs Schiffman et al 2007 – Lancet,370:890 – 907 Chama et al 2005, J ObstetGynecol 25(3):p286-8. CAPITOL HILL CLINIC/HOSPITAL

10. Lack of political will/Commitment • “Women are dying not just because we do not understand the cause but we have not consider their lives worth saving…” MahamudFathalla – 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! CAPITOL HILL CLINIC/HOSPITAL

11. POOR HEALTH SEEKING BEHAVIOUR • Belief 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 fatal • Visit at least a native practitioner • Apathy of Men to women’s health issues. • Lack of economic empowerment of women. • 80% present late CAPITOL HILL CLINIC/HOSPITAL

12. Lack of Awareness and Knowledge • women lack basic health education • Some 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 risk • Health practitioners underestimate level of risk CAPITOL HILL CLINIC/HOSPITAL

13. Weak Health Systems • little existing public health infrastructure • A 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 India CAPITOL HILL CLINIC/HOSPITAL

14. Poverty • Pap 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/HOSPITAL

15. Poverty Index: % Living below Poverty Line. CAPITOL HILL CLINIC/HOSPITAL

16. Cervical Cancer:A Failure of Screening ! • Failure to be screened: 50 – 60 % • Ever • At an appropriate interval • Failure of screening: 40 –50% • Screening did not show an abnormality • False negative • Interpretation error • Smear takers error • Failure to follow up on recommendations of screening program: 10 – 20 % CAPITOL HILL CLINIC/HOSPITAL

17. WHY 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

18. PREVENTIONS • Primary Prevention • Risk reduction • Condom use • Circumcision • Vaccine • Secondary Prevention • Screening CAPITOL HILL CLINIC/HOSPITAL

19. PRIMARY PREVENTION • OBSTACLES • Difficult to change behaviour • Cultural practices • Costly • Political • Religious • Lack of awareness CAPITOL HILL CLINIC/HOSPITAL

20. SECONDARY PREVENTION • Methods of screening • Pap smear • HPV DNA testing • Liquid cytology/Thin prep • Visual inspection of cervix using acetic acid • VILI • MVIA • Cervicograms • Polarprobe • Optical Technologies CAPITOL HILL CLINIC/HOSPITAL

21. SECONDARY PREVENTION • Drawbacks • Cost • Need for specialized skilled personnel • Need for functional laboratories • Follow-up schedules • Lack of resources • Sensitivity/Specificity CAPITOL HILL CLINIC/HOSPITAL

22. What does a Pap smear test involve? • vaginal speculum exam during which a sample of cells from a woman’s 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. CAPITOL HILL CLINIC/HOSPITAL

23. Specimen Preparation for Clinical CytoPathology (Pap Smears) Transfered on the slide (Fixation) Spatula-CytoBrush Papanicolaou staining Pathology Review CAPITOL HILL CLINIC/HOSPITAL

24. Strengths 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. CAPITOL HILL CLINIC/HOSPITAL

25. Limitations of cytology: • Moderate to low sensitivity: • High rate of false-negative test results • Women must be screened frequently • Rater dependent • Requires complex infrastructure • Results are not immediately available • Requires multiple visits • Likely to be less accurate among post-menopausal women CAPITOL HILL CLINIC/ HOSPITAL

26. Assessment Newer Technologies • Fluorescence and reflectance spectroscopy for real-time screening and diagnosis • Quantitative cytology for objective, real-time screening (Hybrid Capture, HPV DNA, mRNA) • Quantitative histo-pathology to relate optical measurements to a quantitative model of progression • Confocal Microscopy and In Vivo ConfocalEndocopy • Visual Inspection( ACA/LI) CAPITOL HILL CLINIC/HOSPITAL

27. New version of the CytoSavant : works with H@E stained specimen CAPITOL HILL CLINIC/HOSPITAL

28. Specimen Preparation for Quantitative Cytology (Thin-Prep) ThinPrep ® Processor Spatula-CytoBrush PreservCyt solution Feulgen-Thionin Staining CytoSavant Automatic Scanning CAPITOL HILL CLINIC/HOSPITAL

29. Multi-spectral digital colposcopy • Multi-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/HOSPITAL

30. Fluorescence Spectroscopy • Fluorescence 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 CAPITOL HILL CLINIC/HOSPITAL

31. Patient 5 SOGON 2007 BENIN CITY

32. Patient 9 CAPITOL HILL CLINIC/HOSPITAL

33. Human Papilloma Virus The Necessary Cause Abounds • Genital 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 lives • The 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? CAPITOL HILL CLINIC/HOSPITAL

34. Five Most Common HPV Types in Invasive Cervical Cancer by Region All Cases Africa 70.4% 71.8% % % HPV Type HPV Type Asia Europe 73.8% 66.9% % % HPV Type HPV Type North American and Australia South and Central America 75.8% 65.1% % % HPV Type HPV Type Smith et al. Unpublished

35. HPV: a challenge for the immune system HPV is designed to evade the natural immune defense mechanisms: • No viraemia • HPV does not kill keratinocytes: • no inflammation • no pro-inflammatory cytokines • poor activation of epithelial APCs CAPITOL HILL CLINIC/HOSPITAL

36. CAPITOL HILL CLINIC/HOSPITAL

37. Basis for Licensure/Cancer Efficacy:Demonstrate Prevention of HPV 16/18-CIN 2/3 + AIS Natural History of HPV Infection:Surrogate Markers for Cervical Cancer 0 to 5 Years Up to 20 Years CIN 3 CIN 2 Sq. Cell Carcinoma InitialHPV Infection PersistentInfection AIS Adeno- Carcinoma CIN 1 Cleared HPV Infection

38. HPV Vaccine Development • Creation of virus-like particles (1991) • Mimic natural virion structure • Generate potent immune response • Contain no DNA • **Non-infectious • **Cannot cause disease L1 L1 L1 CAPITOL HILL CLINIC/HOSPITAL

39. SOGON 2007 BENIN CITY

40. GARDASIL in Summary **Studies conducted in >27,000 subjects in 33 countries • GARDASIL is well-tolerated and safe • GARDASIL is highly effective at prevention of: • Persistent infection with HPV types 6/11/16/18 • Clinical disease caused by HPV types 6/11/16/18 • Protection appears to be durable, with stable antibody levels for at least 3.5 years post immunization • GARDASIL is a prophylactic vaccine and does not treat disease or infection with HPV • GARDASIL does not replace screening CAPITAL HILL CLINIC/HOSPITAL

41. CC is a critical public health problem • GSK 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/HOSPITAL

42. Making Cervical Cancer History 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 worldwide—a cancer that should now be largely preventable • Effective collaboration predicated on shared vision, trust and commitment to advocacy for global cervical cancer control • Funding to support vaccination and screening programs • Research to guide optimal implementation strategies • Realistic 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 CAPITOL HILL CLINIC/HOSPITAL

43. BE SCREENED TODAY BE VACCINATED TODAY

44. POST TEST Answer true or false • Cervical 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 lives • Vaccination alone is the only effective way of preventing ca cervix. • Cervarix is a highly effective vaccine against HPV 11, 16 and 18