1. Human Papilloma Virus

2. HPV

3. CERVICAL WARTS and HSIL

4. CERVICAL WARTS and HSIL

5. Other sites of Warts

6. CERVICAL CANCER

11. HPV Nomenclature Cervical / Vaginal / Vulvar / Anal / Penile Dysplasia Mild Dysplasia Moderate Dysplasia Severe Dysplasia Carcinoma in-situ Intraepithelial Neoplasia CIN I VIN 1 VAIN 1 CIN 2 VIN 2 VAIN 2 CIN 3 VIN 3 VAIN 3 Squamous Intraepithelial Lesion (SIL) Low Grade SIL (LSIL) High Grade SIL (HSIL) High Grade SIL (HSIL)

13. Cervical Carcinogenesis

18. HPV Vaccine

20. Natural History of HPV Infection: Surrogate Markers for Cervical Cancer 0–1 Year 0–5 Years 1–20 Years HPV Infection Low Grade Lesions High Grade Lesions Invasive Cancer Demonstrate efficacy against high grade lesions LSIL (CIN1) or HSIL (CIN2/3), low- or high-grade squamous intraepithelial lesion. CIN= Cervical Intraepithelial Neoplasia

21. Vaccine should demonstrate efficacy against CIN2/3 rather than focusing on antibody titers Human Papillomavirus and HPV Vaccines: technical information for policy –makers and health professionals Initiative for Vaccine Research Department of Immunization, Vaccines and Biologicals World Health Organization have been reviewed in depth76. For vaccine licensing, the endpoint of CIN2/3 or AIS has been widely accepted as a proxy for cervical cancer that can be studied ethically. This endpoint can be evaluated among young women. In children or young adolescents, however, it is not practical to study this endpoint, since cervical specimens would be required, and the endpoint is rare in young people. Bridging studies are therefore conducted, in which the antibody responses of young people are compared with those of women for whom data on the clinical endpoint (CIN2/3 or AIS) will be available. WHO Guidelines Guidelines to assure the quality, safety and Efficacy of recombinant human papillomavirus Virus-like particle vaccines. Expert committee on biological standardization Geneva, 23 to 27 october 2006. available at http://www.who.int/biologicals/publications/trs/areas/vaccines/human_ papillomavirus/HPVg%20Final%20BS%202050%20.pdf accessed on January 22, 2009.

22. What is the relevance of neutralizing and non-neutralizing antibodies ?

23. Antibody color legend: Blue = Neutralizing antibodies Yellow = Nonneutralizing antibodies Chen XS, et al. Molecular Cell. 2000;5:557–567. Neutralizing antibodies prevent HPV infection Non-neutralizing antibodies do not prevent infection No antibodies – viral infection Cell surface receptors Neutralizing Antibodies and HPV Infection

24. Types of antibodies after HPV vaccination Neutralizing and Non neutralizing antibodies Bivalent HPV Vaccine measures Quadrivalent HPV Vaccine measures Neutralizing + Non neutralizing antibodies Neutralizing antibodies ELISA Assay – ELISA units/ml cLIA Assay – milli Merck units/ml Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y

25. Does HPV vaccine protect any disease other than cervical cancer?

27. What is the efficacy of HPV vaccine?

28. Efficacy of Gardasil HPV induced lesions Cervical Cancer & Precancers (Grade 2/ 3) 1 Vulvar/ Vaginal Precancers (Grade 1- 3) 2 Genital Warts 2 Protection by QHPV 98% 100% 99% 1. The Future II Study Group. Lancet 2007; 369: 1861–68 2.Garland SM et al. New Engl J Med. 2007;356:1928–1943.

30. What is the difference between two HPV vaccines?

31. Quadrivalent Vs Bivalent Vaccine CIN=cervical intraepithelial neoplasia; HPV=human papillomavirus. aProven in combined analysis of Phase II and III trials. bIn postlicensing evaluation (http://www.who.int/vaccine_safety/en/). cIn clinical trials. dCorresponds to duration of trials in 2007, Bosch et al. BJC 2008; 98: 15-21

32. For how long does HPV vaccine provide protection?

34. QHPV: Demonstrated Immune Memory GMT = geometric mean titer *Similar response with the other three types of HPV within vaccine Olsson SE et al. Vaccine 2007;25:4931-4939.

35. What is the efficacy in women aged 27 – 45 yrs against vaccine type related CIN 2/3?

36. Efficacy of Gardasil HPV 6/11/16/18-Related Persistent Infection or Cervical/ Vulvar/ Vaginal Disease (Women 24 - 45 yrs of Age) Per-Protocol Efficacy Population* – Primary Endpoint Only Gardasil has demonstrated efficacy against CIN 2/3 in women aged 27 – 45 yr 1. Luna J et al. Poster presented at: 24th International Papillomavirus Congress; November 3-9, 2007; Beijing, China. Presentation No. PA1-04. 2. Worldwide Product Circular. GARDASIL™ [Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine]; WPC-GRD-I-122007. *Efficacy after three doses in women 24 to 45 years of age naïve to the relevant type at baseline

37. Are HPV vaccines safe?

38. Vaccine Profile: Side Effects No serious vaccine related adverse effects with both vaccine Consensus Recommendations on Immunization, Indian Academy of Pediatrics Committee On Immunization (IAPCOI). Indian Pediatrics 2008; (45)635-648 12% 4% Systemic: Fever 40% 25% Local: Swelling and erythema 90% 83% Local: Pain at inj. Site ( mild to moderate) Bivalent Quadrivalent Side Effects

39. What are the recommendations for HPV vaccine?

44. Indian and United States Organizations IAP – Indian Academy of Pediatrics FOFSI - The Federation of Obstetric & Gynaecological Societies of India AAP = American Academy of Pediatrics ACHA = American College Health Association ACOG = American College of Obstetricians and Gynecologists AAFP = American Academy of Physicians SAM = Society for Adolescent Medicine Recommendations by US based organizations are only for Gardsil as it is the only USFDA approved HPV vaccine 1. http://www.acog.org/from_home/publications/press_releases/nr08-08-06.cfm, visited on7th March 2008 2. American Academy of Family Physicians. Practice guidelines: ACIP releases recommendations on quadrivalent human papillomavirus vaccine. Am Fam Physician. 2007;75(9). Available at: http://www.aafp.org/afp/20070501/practice.html. Accessed May 30, 2007. 3. Society for Adolescent Medicine. Human papillomavirus (HPV) vaccine: a position statement of the Society for Adolescent Medicine. Available at: http://www.adolescenthea lth.org/positionstatement_HPV_vaccine.pdf. Accessed May 16, 2007. 4. American College Health Association (ACHA). Vaccine Preventable Diseases Committee. Recommendations for institutional prematriculation immunizations. August 2006. Available at: http://www.acha.org/info_resources/guidelines.cfm. Accessed May 16, 2007. 5. PEDIATRICS Volume 120, Number 3, September 2007 6. INDIAN PEDIATRICS: VOLUME 45--AUGUST 17, 2008 7. The Federation of Obstetric & Gynaecological Societies of India (FOGSI). Recommendations for Vaccination against Human Papilloma Virus (HPV) Infection For the prevention of Cervical Cancer. Available at http://www.fogsi.org/hiv_vaccine.html. accessed on 20th Feb 20009 √ √ √ √ FOGSI √ √ √ √ IAP √ √ √ √ ACHA Recommendations ACOG AAFP SAM AAP Routine vaccination in females 11-12 years old & catch-up vaccination in 13-26 year olds √ √ √ √ Females 9-10 years old may be vaccinated √ √ √ √ Vaccinate regardless of previous HPV infection or abnormal Pap test results √ √ √ √ Continue Pap testing after vaccination √ √ √ √

47. Should screening be done prior to vaccination?

49. Should vaccine be administered in sexually active women/ women with abnormal cytology?

51. Can HPV vaccine be given in lactating women?

53. Can HPV vaccine be given in Pregnant women?

56. GARDASIL ® is recommended for females aged 9 through 26 years (see INDICATIONS). DOSE, METHOD OF ADMINISTRATION AND USAGE

60. Preventive Health Care is right of every woman. . . Let’s execute & offer;

64. Mrs. Reena (25yr) Post Delivery Her follow up visit @ 6weeks ROUTINE Check up + Counseling PAP, 1st dose of HPV Enroll in Reminder System PAP Result PAP Result Abnormal PAP Result Normal Further Investigations Vaccination 2nd Dose Vaccination 3rd Dose

65. Ms Rosy ~ DUB Complaint of Bleeding P/V Follow up ~ No bleeding PAP Result Abnormal PAP Result Normal Further Investigations Vaccination 2nd Dose Vaccination 3rd Dose Investigation & Management ROUTINE Check up + Contraception Counseling PAP, 1st dose of HPV Enroll in Reminder System

66. Kamini 22 yr ~ Spontaneous abortion Complaint of Bleeding P/V Follow up@ 6 wk ~ No bleeding Enroll in Reminder System PAP Result Abnormal PAP Result Normal Further Investigations Vaccination 2nd Dose Vaccination 3rd Dose + contraception counselling USG, D&E, Lab Ix ROUTINE Check up + Contraception Counseling PAP, 1st dose of HPV

67. Mrs. Sadhna (26yr) For IUCD Insertion Clinic visit on day 5 of M.Cycle for IUCD Insertion Enroll in Reminder System PAP Result Abnormal PAP Result Normal Further Investigations Vaccination 2nd Dose Vaccination 3rd Dose IUCD Up exam ROUTINE Check up + Contraception Counseling PAP, 1st dose of HPV PAP Result