Hpv vaccine

HPV and its prevention

1. HPV Dr Menaal Kaushal JR II Department of S P M

2. Contents Introduction Problem Statement Clinical manifestation Screening Prevention- Vaccination, Condom, Circumcision Special Cases& Controversies: Girls 9- 12 years Unmarried Girls 13- 26 years Unmarried older women Married HPV negative women HPV positive women Men

3. Introduction ds- DNA virus- Papillomavirus >100 HPV types Needs keratinocytes- “Skin virus ” Skin or Mucous membranes- about 40 genital HPV types Of which, 15 -18 genital types associated with cancer

4. HPV Classification “ Low Risk ” HPV Genital warts Low grade cervical dysplasia “ High Risk ” HPV Low and high grade cervical dysplasia Cervical Cancer

5. Cervical Dysplasia Classification Basement Membrane Basal Cell Layer Histology of Cervical Squamous Epithelium Low Risk HPV High Risk HPV

6. High and Low Risk HPV Oncogenic Potential Clinical Manifestations Types Low CIN I Genital warts 6, 11 Low CIN I 40,42,43,44,54 55,57,61,84 High CIN I-III carcinoma 16,18,31,33,35, 39,45,51,52,56, 58,59,68,73,82

7. Detection of HPV Types in Cervical Cancer

8. Problem Statement Human papillomavirus (HPV) is an extremely common STD , with an estimated 80 percent of sexually active people contracting it at some point in their lives; Incidence: 14 million new infections occur yearly. Prevalence: About 79 million people (both men and women) are thought to have an active HPV infection at any given time . SKIN contact, not body fluids Genital HPV is EVERYWHERE!

9. In India In India, Ca Cervix is the No 1 cancer among women, with an incidence of 27.0 per 100,000 women and an age standardized mortality rate as high as 45.2 per 100,000 women (2008)

10. Epidemiologic Relationships of HPV Well Established: Cervical Dysplasia and Cancer Genital Warts Recurrent Respiratory Papillomatosis As well as: Anogenital cancers (vulvar, penile, vaginal) Head and Neck Cancer (esophagus, pharynx)

11. In the West, 30% of oral carcinoma is related to HPV. It is commonly seen in ages 20 - 39 years The risk of contracting oropharayngeal cancer (cancer of the tonsils, back of throat or base of the tongue) heightens 3.4 times with 6 or more oral sex partners The survival rate for those with HPV-positive head and neck tumors is 85% in non-smoking people. The survival rate drops down to 45-50% for smokers .

12. Global Perspective on Cervical Cancer 2nd most common cancer in women The cancer that kills more women on a world wide basis every year >250,000 women die each year world wide One woman dies every two minutes from cervical cancer Leading cause of death from cancer in developing countries

13. HPV Transmission Sexual- Intercourse Genital (non-penetrative), oral, digital contact (skin to skin contact) Condoms help, but not completely protective Non-sexual Mother to newborn (vertical transmission - rare) Possibly via fomites (underwear, equipment) Can be seen in virgins (rare ) SKIN contact, not body fluids

14. Clinical Manifestation Asymptomatic Persisted Cleared S ymptomatic If an HPV infection is persistent past the age of 30, there is a greater risk of developing cervical cancer .

15. Most HPV Infections Resolve HPV “ Clearance ” 80 - 90 % of infections will resolve in 2 years Average duration of infection 9 - 13 months Unclear if virus is eradicated or latent HPV “ Persistence ” 10 - 20 % of infections persist Major risk factor for developing cancer Risk factors for persistence not well understood * Clearance and persistence is age related

16. Age-related Trends in HPV Infection in Women

17. Age Specific Rates of HPV-Related Genital Cancers in the U.S.

18. HPV During Adolescence Risk of Genital HPV Infection from Time of First Sexual Intercourse ~50% Cumulative Incidence

19. HPV in Adolescence Of all new HPV infections, 74% occur in the 15 - 24 year old age group Adolescents particularly vulnerable Biological : Immune immaturity Large transformation zone of cervix Behavioral (In the West)

20. Why are Adolescent Women More Susceptible to HPV? Large transformation zone

21. The New ACOG Screening Guidelines (Oct 2012) Pap tests should begin at age 21 , regardless of sexual history Pap testing should not be done for most women more often than every 3 years - NO traditional "annual Pap" regimen, but those with abnormal Paps will be tested more often (yearly) Rather than using a Pap test alone, HPV/Pap co-testing is now the preferred method of screening women age 30 and over. Such co-testing should only occur once every 5 years with women who have normal test results

22. HPV testing should NOT be done in women under age 30 other than as follow-up to unclear Pap test results Cervical cancer screening can end for most women at age 65 , provided she has no history of cervical pre-cancer or cancer, and has had at least three consecutive, normal Pap tests (or two normal HPV tests) within the last 10 years. Women at greater risk for cervical cancer (e.g., those with a history of cervical pre - cancer or cancer and those who are HIV-positive or otherwise have weakened immune systems) may require screening more frequently

23. HPV VLP Vaccines Bivalent ( Cervarix ) : HPV 16 {0, 1, 6} HPV 18 ASO4 Adjuvant (MPL + Alum) Quadrivalent (Gardasil) : HPV 16 {0, 2, 6} HPV 18 Aluminum as adjuvant HPV 6 HPV 11 70% of Cervical Ca 70% of Cervical Ca 90% of Genital Warts IM Injections at 0, 1 or 2, and 6 months

24. Vaccine Schedule Dosing schedules with the vaccines are at 0, 1 to 2 months, and 6 months. Minimum intervals are 4 weeks between doses 1 and 2, 12 weeks between doses 2 and 3, and 24 weeks between the first and third doses. It is likely that variations in scheduled doses do not seriously impair the vaccines’ effectiveness; therefore, the vaccine series should not be restarted if the schedule is interrupted.

25. Structural model of papillomavirus VLP * VLP (~20,000 kD ) 72 Capsomeres L1 Capsomere (~280 kD ) 5 x L1 L1 Protein (55 – 57 kD) Assembly of HPV VLPs VLP = Virus - like particle

26. IMMUNOGENICITY RESULTS (PER PROTOCOL POPULATION): HPV; VLP; PCR

27. Immunologic Titers To HPV 6, 11, 16, & 18 After Vaccination HPV 6 HPV 16 HPV 18 HPV 11

28. Sustained Seropositivity And High Antibody Levels Up To 4.5 Years 1 10 100 1000 10000 month 0 month 7 month 12 month 18 [M25-M32] [M33-M38] [M39-M44] [M45-M50] [M51-M53] 0% 17% 0% 0% 12% 11% 12% 10% 10% 6% 100% 100% 100% 99% 99% 99.7% 100% 100% Vaccine HPV-16 IgG Placebo HPV-16 IgG % seropositive log (EU/ml) Months follow up time Initial efficacy Extended follow up Natural Infection 17 fold higher HPV-16

29. Months follow up time Sustained Seropositivity And High Antibody Levels Up To 4.5 Years 100% 100% 99% 99% 99% 99.7% 100% 100% 10% 1 10 100 1000 10000 month 0 month 7 month 12 month 18 [M25-M32] [M33-M38] [M39-M44] [M45-M50] [M51-M53] log (EU/ml) Initial efficacy Extended follow up 0% 17% 0% 0% 9% 13% 16% 12% 7% Vaccine HPV-18 IgG Placebo HPV-18 IgG % seropositive Natural Infection 14 fold higher HPV-18

30. Efficacy Against Incident Infection by Other High Risk HPV Types HPV16/18 Vaccine: ITT Analysis HPV Type # Vaccine # Placebo Efficacy (95%CI) 16 1 16 94 (53-99) 18 5 100 (24-100) 45 1 17 94 (63-100) 31 14 30 54 (11-78) 33 12 13 1 ( <0 - 61) 52 40 48 19 (-27 - 48) 58 14 16 14 (- 88 - 61 )

31. Low-risk HPV types Phylogenetic Tree Anogenital HPV Types High-risk HPV types 2 57 3 10 44 13 6 11 7 40 43 32 42 30 53 56 66 51 26 34 45 39 68 18 35 16 31 58 33 52

32. Estimated Distribution of Time Participants Remained Free of HPV

33. SPECIAL SITUATIONS Equivocal or abnormal Pap test OK Positive HPV test OK Genital warts OK Immunosuppression OK Lactating women OK

34. Precautions and Contradictions Moderate or severe acute illnesses: should be deferred until after the illness improves History of hypersensitivity or severe allergic reaction to yeast or to any vaccine component Pregnancy

35. Key Issues Remaining Pap smear screening recommendations will NOT change. Only HPV 16/18 are included in the vaccine; 13 other types implicated in Cervical Cancer Should older women (>26 years of age) be vaccinated? YES, older women who are not with abnormal Pap, and not currently HPV infected, can be vaccinated

36. When the percentage of girls getting vaccinated are in the 30 to 40 percent range, vaccinating boys is suggested to have a substantial enhancing impact on trying to protect those girls who are not vaccinated. This would provide "herd immunity." Boys don't get cervical cancer, but they can transmit HPV. So vaccinating boys would reduce the amount of HPV circulating in the population HPV Among Boys

37. Age-Specific Incidence of HPV Infection in Men

38. Incidence of Anal HPV Infection in HIV-negative MSM

39. Increasing Incidence of Anal Cancer Increasing Incidence of Anal Cancers

40. Anal High-Grade Squamous Intraepithelial Lesions: Progression Over 3 Years

41. Projected Number of Patients With Oropharyngeal Cancer

42. Recommendations for Quadrivalent HPV Vaccine in Males

43. Thank You