Hpv vaccine

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HPV and its prevention

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  • The reason for moving away from the annual Pap is evidence shows little gain in testing more often, but potential harm of “over screening” such as follow-up exams (like colposcopy/biopsy) and treatment to the cervix, especially with women of child-bearing age.
  • Hpv vaccine

    1. 1. HPV Dr Menaal Kaushal JR II Department of S P M
    2. 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. 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. 4. HPV Classification “Low Risk” HPV Genital warts Low grade cervical dysplasia “High Risk” HPV Low and high grade cervical dysplasia Cervical Cancer
    5. 5. Cervical Dysplasia Classification Low Risk HPV Histology of Cervical Squamous Epithelium Basal Cell Layer Basement Membrane High Risk HPV
    6. 6. High and Low Risk HPV Oncogenic Clinical Potential 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. 7. Detection of HPV Types in Cervical Cancer 11.4 16 18 45 31 33 58 52 35 Others 0.4 0.6 3.20.2 3.9 3.3 54.9 22.1 Europe Europe 0.5 0.5 4.4 0.5 2.2 0.8 4.2 0.8 4.4 4.2 2.9 Asia 16 18 0.5 13.5 20.8 16 16 45 18 18 45 45 31 5.4 2.9 56 17.2 4.2 31 33 58 1 3.4 Africa 17.2 2 16 4.5 56 1.4 52 35 Others 15.3 43.4 31 33 58 33 58 52 35 Oth 13 3.3 52 16 31 3.1 2 17.5 1.6 Latin America 18 45 18 35 33 58 Others 1.6 2.6 45 7.9 31 2.9 4 51.7 7 5.5 10.6 50.2 52 14.1 33 35 58 52 Others 35 Others
    8. 8. Genital HPV is Problem Statement EVERYWHERE! 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
    9. 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. 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. 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. 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. 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. 14. Clinical Manifestation Symptomatic • Persisted Asymptomatic • Cleared If an HPV infection is persistent past the age of 30, there is a greater risk of developing cervical
    15. 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. 16. Age-related Trends in HPV Infection in Women Mean Prevalence 2.5 2 1.5 Oncogenic Non-oncogenic 1 0.5 0 <25 25- 3534 44 45- 55- >65 54 64 Age group
    17. 17. Age Specific Rates of HPV-Related Genital Cancers in the U.S. 20 Cervix Vulva 15 Penis 10 Anus Female Vagina 5 Anus Male Age Range in Years 85+ 80-84 75-79 70-74 65-69 60-64 55-59 50-54 45-49 40-44 35-39 30-34 25-29 20-24 0 15-19 Incidence per 100,000 25
    18. 18. HPV During Adolescence Risk of Genital HPV Infection from Time of First Sexual Intercourse 1 Cumulative Incidence of HPV 0.9 0.8 0.7 ~50% Cumulative Incidence 0.6 0.5 0.4 0.3 0.2 0.1 0 0 4 8 12 16 20 24 28 32 36 40 44 Months Since First Intercourse 48 52 56 60
    19. 19. HPV in Adolescence Of all new HPV infections, 74% occur in the 1524 year old age group Adolescents particularly vulnerable • Biological: • Immune immaturity • Large transformation zone of cervix • Behavioral (In the West)
    20. 20. Why are Adolescent Women More Susceptible to HPV? Large transformation zone
    21. 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. 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. 23. HPV VLP Vaccines Bivalent (Cervarix) : {0, 1, 6} HPV 16 HPV 18 70% of Cervical Ca ASO4 Adjuvant (MPL + Alum) Quadrivalent (Gardasil) : HPV 16 {0, 2, 6} HPV 18 70% of Cervical Ca HPV 6 HPV 11 90% of Genital Warts Aluminum as adjuvant IM Injections at 0, 1 or 2, and 6 months
    24. 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. 25. Assembly of HPV VLPs Structural model of papillomavirus VLP* VLP (~20,000 kD) L1 Protein (55–57 kD) L1 Capsomere (~280 kD) 5 x L1 VLP = Virus- like particle 72 Capsomeres
    26. 26. IMMUNOGENICITY RESULTS (PER PROTOCOL POPULATION): HPV; VLP; PCR
    27. 27. Immunologic Titers To HPV 6, 11, 16, & 18 After Vaccination HPV 6 HPV 16 HPV 11 HPV 18
    28. 28. Sustained Seropositivity And High Antibody Levels Up To 4.5 Years log (EU/ml) 10000 HPV-16 100% % seropositive 100% 1000 99.7% Vaccine HPV-16 IgG Placebo HPV-16 IgG 99% 100% 99% 100% 100% 17 fold higher 100 Natural Infection 10 6% 0% 17% 0% 0% 10% 10% 12% 11% 12% 1 month 0 month 7 month 12 month 18 [M25-M32] [M33-M38] [M39-M44] [M45-M50] [M51-M53] Initial efficacy Extended follow up Months follow up time
    29. 29. Sustained Seropositivity And High Antibody Levels Up To 4.5 Years log (EU/ml) HPV-18 10000 % seropositive 100% 100% 1000 99.7% Vaccine HPV-18 IgG Placebo HPV-18 IgG 99% 99% 99% 100% 100 14 fold higher Natural Infection 10 10% 100% 17% 0% 0% 0% 7% 12% 16% 13% 9% 1 month 0 month 7 month 12 month 18 [M25-M32] [M33-M38] [M39-M44] [M45-M50] [M51-M53] Initial efficacy Extended follow up Months follow up time
    30. 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 0 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. 31. Phylogenetic Tree Anogenital HPV Types 6 11 2 57 3 10 13 7 40 44 43 32 42 Low-risk HPV types 30 16 35 31 33 58 52 34 18 45 39 68 53 56 66 26 51 High-risk HPV types
    32. 32. Estimated Distribution of Time Participants Remained Free of HPV
    33. 33. SPECIAL SITUATIONS Equivocal or abnormal Pap test OK Positive HPV test OK Genital warts OK Immunosuppression OK Lactating women OK
    34. 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. 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. 36. HPV Among Boys 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
    37. 37. Increasing Incidence of Anal Cancers
    38. 38. Thank You

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