1. CERVICAL CANCER & OTHER HUMAN PAPILLOMAVIRUS- RELATED DISEASES Dr.Ahmed Eltigani Elmahdi Hussain Consultant Obstetrician & Gynaecologist, IRELAND

2. Incidence of Cervical Cancer In Europe Globocan 2002: ASR (World) < 1.5 < 0.4 <16.6 < 4.4 Age-adjusted incidence rates per 100,000 women per year < 7.9 38 countries: European Union except Cyprus (24 countries) + Iceland, Norway, Switzerland, Belarus, Bulgaria, Moldova, Romania, Russian Federation, Ukraine, Albania, Bosnia Herzegovina, Croatia, Macedonia, Serbia and Montenegro. 27 countries: European Union except Cyprus (24 countries) + Iceland, Norway, & Switzerland (3 countries). EUROPE (38 COUNTRIES): 60,000 new cases per year EUROPE (27 COUNTRIES): 33,386 new cases per year

3. * Ovary, Fallopian tube, broad ligament, round ligament, parametrium, and uterine adnexa. European Union except Cyprus (24 countries) + Iceland, Norway, & Switzerland (3 countries). Age-standardized (World) incidence & mortality rates EUROPE INCIDENCE MORTALITY 4.9 5.4 7.5 34.0 10.4 0 10 20 30 40 Thyroid Ovary &…* Melanoma of skin Cervix uteri Breast Number of cases per 100,000 women per year 1.3 1.3 1.7 2.0 5.7 0 2 4 6 Colon and rectum Brain, nervous system Lung Cervix uteri Breast SOURCE: GLOBOCAN 2002.

4. Cervical cancer is the second most frequent cancer in young women (15-44 years) in Europe 1 1. Ferlay et al. Globocan 2002: Cancer incidence, mortality and prevalence worldwide. IARC Cancer-Base No.5, version 2. Lyon. IARC Press, 2004. 2. Cancer Research UK, Cancer Mortality Figures 2004 http://info.cancerresearchuk.org/images/excel/cs_mort_t6.2.xls Breakdown of cancers in the young European female population (15-44 years) in 2002 21 women die each week on average in the UK 2

8. Human papillomavirus types 6,11,16 & 18 are four common types affecting women’s health 1.Clifford, GM et al. Br J Cancer 2003; 88: 63-73. 2.Daling JR, et al. Gynecol Oncol 2002; 84: 263-270 3.Madeleine et al. J Natl Cancer Inst 1997;89:1516–1523. 4.Clifford GM, et al. Br J Cancer 2003; 89: 101–105 5.Sotlar K, et al. J Clin Microbiol 2004; 42: 3176-3184. 6.van Beurden M, et al. Cancer 1995; 75: 2879-2884. 7.Hording U, et al. Gynecol Oncol 1995; 56: 276–279. 8.Clifford GM, et al. Cancer Epidemiol Biomarkers Prev 2005; 14:1157-1164. 9.von Krogh G. Eur J Dermatol 2001; 11: 598-603. 10.Wieland U, Pfister H. Human Papilloma Virus: A clinical atlas. Ullstein Mosby; 1997. p1-18.

12. Circumcision Castellsagué et al, NEJM 2002 Male circumcision reduces the risk of HPV infection in men and of cervical cancer in the female partner

13. DISEASE CAUSED BY HPV 6/11 Causative agent of genital warts Causative agent of JORRP

17. In women, peak exposure to human papillomavirus occurs in late teens and early twenties Sanofi Pasteur MSD Data on File 2006 06/004

18. Percentage of 15 year old girls who have had sexual intercourse by country Adapted from Ross J, Godeau E, Dias S. Sexual health. In: Currie et al. Eds. Young people’s health in context. Health behaviour in school-aged children study : international report from the 2001/2002 survey. WHO Europe;2004.p. 153-160.

19. Estimated HPV DNA prevalence in the world (Meta-analysis of 67 studies involving 139,777 cytologically normal women) GLOBAL 10.2% (10.0-10.5) AFRICA 23.4% (22.0 - 24.8) AMERICA 12.8% (12.1 - 13.5) EUROPE 8.2% (7.9 - 8.6) ASIA 7.6% (7.2 - 8.1)

20. Which specific HPV types are important in cervical cancer?

23. Cervical Intraepithelial neoplasia (CIN1) 1 Vulval Intraepithelial neoplasia (VIN) 4 Cervical Intraepithelial neoplasia (CIN 2/3) 2,3 Genital warts 6,7 Vaginal Intraepithelial neoplasia (ValN) 5 1.Clifford GM etal. Cancer Epidemiol Biomarkers Prev 2005; 14:1157 – 1164 2. Clifford GM, Smith JS, Aguado T et al. Comparison of HPV type distribution in high-grade cervical lesions and cervical cancer: A meta-analysis. Br J Cancer 2003; 89: 101–105 3. Sotlar K, Diemer D, Dethleffs A et al. Detection and typing of human papillomavirus by E6 nested multiplex PCR. J Clin Microbiol 2004; 42: 3176-3184. 4.Madeleine MM, Daling JR, Carter JJ et al. Cofactors with human papillomavirus in a population-based study of vulvar cancer.J Natl Cancer Inst 1997;89:1516–1523. 5. Daling JR, Madeleine MM, Schwartz SM et al. A population-based study of squamous cell vaginal cancer: HPV and cofactors. Gynecol Oncol 2002; 84: 263-270.6.Von Krogh G. Eur J Dermatol 2001;11:598-603. 7. Wieland U., Pfister H. In:Gross, Barrasso eds Human papillomavirus: A clinical atlas.Ullstein Mosby; 1997.p1-18

25. Infection with human papillomavirus can lead to genital warts 4,174 people in Ireland were diagnosed in 2004 with genital warts which is an increase of 4.8% compared with 2003 1

27. UK burden of disease – cervical cancer 17.9% 7.3% CC Cases * Management of abnormal findings CC Screening Hospital days for existing cervical cancer cases New cervical cancer cases £104.3 million £34.5 million £33.3 million £13.5 million 56.2% 18.6% 25.2% *No data for NI Brown RE et al. Curr Med Res Opin 2006; 22 : 663–670 Total estimated cost of cervical cancer from screening to management of the disease in the UK in 2003 is around £185.6 million Estimated cost of disease management

30. Vaccines- prepared from exogenously expressed HPV major L1 capsid proteins VLPs (virus-like particles) and have been induce HPV type-specific antibody responses

32. * CIN = Cervical intraepithelial neoplasia ** World Health Organisation *** Food and Drug Administration US Proven efficacy in the prevention of cervical cancer against a truly predictive clinical endpoint 0 years 10 + years 1. Adapted from Franco EL, Harper DM. Vaccine 2005; 23:2388-94 2. Sanofi Pasteur MSD Data on File 06/008 2

33. Rationale for designing a quadrivalent HPV vaccine 1. Clifford, G. M et al. British Journal of Cancer, 88, 63-73. 2003 2. Von Krogh G. Eur J Dermat . 2001;11: 598-603. 3. Koutsky L. Am J Med. 1997; 102: 3-8. Reason for choice of the human papillomavirus types Anticipated benefits 41

36. THEORETICAL IMPACT OF A VACCINE INCLUDING HPV Types 6, 11, 16 & 18 67-71% 52-60% ~35% ~20-30% ASCUS: Atypical Squamous Cell of Undetermined Significance L/HSIL: Low/High Grade Squamous Intraepithelial Lesion ICC: Invasive Cervical Cancer ICC ASCUS LSIL HSIL POTENTIAL REDUCTION Months Years Decade(s)

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