Flash Player 9 (or above) is needed to view presentations.
We have detected that you do not have it on your computer. To install it, go here.

Like this presentation? Why not share!

HPV Vaccines






Total Views
Views on SlideShare
Embed Views



0 Embeds 0

No embeds



Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
Post Comment
Edit your comment

HPV Vaccines HPV Vaccines Presentation Transcript

  • HPV Vaccines Dr W H LI Queen Elizabeth Hospital 5 August 2007
  • Content
    • Introduction
    • Basic Information for Human Papillomavirus
    • HPV Vaccine Target Antigens
    • Vaccine Types
    • Phase II/III clinical trials
    • Gardasil / Cervarix
    • FAQ
    • Conclusion
  • Introduction (1)
    • Cervical cancer is one of the leading causes of cancer mortality worldwide
    • Estimated to have 470 000 new cases and 230 000 deaths every year worldwide with 80% of the cases occurred in developing countries
    View slide
  • Cervical Cancer in Hong Kong 439 (2004) 126 (2005) View slide
  • Introduction (2)
    • Even though screening reduces the risk of cervical cancer, it does not prevent pre-cancerous lesions, which need careful / expensive follow-ups and intervention
    • Although there are effective treatment for CIN lesions, recurrence still occur and management of recurrent disease maybe difficult
    • Establishing screening programs is not the only solution to the problem
  • Introduction (3)
    • Especially in developing / under-developed countries, limited national screening program, late presentation of disease and limited treatment facilities are the main obstacles in fighting against cervical cancer
    • High morbidity / mortality for advanced disease
    • New modality for prevention and treatment of cervical cancer is required
  • Introduction (4) ≥ 95% Cervical >70% Anal 50% Penile >50% Vulval 50% Vaginal Association with HPV Cancer Human papillomavirus is the perfect candidate to investigate for Prevention and Treatment of Anogenital Tract Cancers
  • Introduction (5)
    • HPV infection is primarily transmitted by genital contact:
      • Penetrative sexual intercourse
      • Oral-genital, manual-genital, genital-genital
      • Sharing sex toys / auto-innoculation (from your own hand to your genital tract)
    • Non sexual route include transmission from mother to newborn baby (Caesarean section not indicated)
  • Introduction (6)
    • Up to 70% of sexually active women will become infected with HPV during their sexual life, but the majority of these infections are transient with 70-90% spontaneously cleared within 12-30 months
    • High-risk HPV highly associated with pre-cancerous cervical lesions and cervical cancer (up to 99.7% with highly sensitive PCR tests)
    • Most important factor is persistent type-specific high-risk HPV infection
  • Introduction (7)
    • Most prevalent HPV types associated with cervical cancer are:
      • HPV 16 (54.3%) HPV 18 (12.6%)
      • HPV 45 (4.2%) HPV 31 (4.2%)
      • HPV 33 (4.3%) HPV 58 (3%)
      • HPV 52 (2.5%)
    *Prevalence of HPV 58 in Chinese may be up to 23.8%
  • Introduction (8)
    • HPV vaccines that protect against HPV infections theoretically prevent women from developing pre-cancerous lesions and cervical cancer (Prophylactic vaccine)
    • HPV vaccine that control the HPV infected cells theoretically treat women with active disease or act as adjuvant agent (Therapeutic vaccine)
  • Introduction (9)
    • HPV type 16 and 18 present in
      • ~70% of Ca cervix cases
      • ~50 % HGSIL cases
      • ~14-25% LGSIL cases
    • Provides an estimate of the potential impact of a vaccine against HPV-16 and HPV-18
  • Basic Information for Human Papillomavirus
  • Human Papillomavirus
  • Human Papillomavirus
    • Non enveloped virions consists of 72-capsomere capsid (outer coat) containing the double stranded circular DNA genome
    • Capsid made up of the major structural protein L1 (80%) and minor structural protein L2 (20%)
  • HPV genome
    • 3 regions:
      • Long control region (LCR) without coding potential
        • Origin of replication and regulation of HPV gene expression
      • Regulatory (early) proteins E1-E8
      • Structural (late) proteins L1 and L2 (capsid)
  • Gene Function/HPV Proteins
    • L1 : Major capsid protein: can form virus-like particles.
    • L2 : Minor capsid protein: possible DNA packaging protein
    • E1 : DNA-dependent ATPase, ATP dependent helicase: allow unwinding of the viral genome and act as an elongation factor for DNA replication.
    • E2 : Responsible for recognition and binding of origin of replication. Exists in two forms: full length (transcriptional transactivator) and truncated (transcriptional repressor). The ratio of these found in the heterotrimeric complex formed before complexing with E1 regulates transcription of viral genome.
    • E3 : ???
    • E4 : Late Expression: C terminal binds intermediate filament, allowing release of virus-like particles. Also involved in transformation of host cell by deregulation of host cell mitogenic signalling pathway.
    • E5 : Obstruction of growth suppression mechanisms: e.g EGF receptor; activation of mitogenic signalling pathways via transcription factors: c-Jun and c-Fos (important in ubiquitin pathway degradation of p53 complex by E6). Inactivation of p21 (p53 induced expression halts cell cycle until DNA is proof-read for mutations).
    • E6 : E6 Transformation of host cell by binding p53 tumour suppressor protein.
    • E7 : Transforming protein, binds to pRB
    • E8-E2 fusion protein : Long distance transcription and replication repressor protein
  • HPV Proteins
    • Structural proteins L1 and L2:
      • Building the capsid (outer coat)
    • Replication proteins E1 and E2
      • Viral replication inside the infected cells
    • Oncoproteins E6 and E7
      • Inhibiting tumour suppressor genes (p53 and pRB)
  • Life Cycle
    • After HPV infection, early (replication) proteins (E1, E2, E6 and E7) are expressed within the basal epithelial layers and viral replication occurs
    • As infected cells reach the surface, late proteins (structural) L1 and L2 proteins are produced and allow shedding of mature virions with exfoliated cells
  • Tumourigenesis
    • Majority of tumour showed integration of HR HPV DNA into host genome
    • Integration disrupts the HPV virus in the E2 open reading frame.
    • Loss of E2 increase expression of E6 and E7 leading to uncontrolled proliferation and tumour formation
  • HPV Vaccine Target Antigens
    • Capsid proteins L1 and L2 (Viral entry)
    • Replication proteins E1 and E2
    • Oncoproteins E6 and E7
  • HPV Vaccine Target Antigens (1)
    • Capsid proteins L1 and L2 (outer coat of the HPV particles)
      • Interact with the surface molecules of human epithelial cells during early stages of infection to gain entry for the viral DNA
      • Ideal targets for prophylactic but not therapeutic vaccines since L1/L2 are not present when HPVs are integrated into tumour cells
      • Most candidate vaccines target L1 since L1>L2 for 30x
  • HPV Vaccine Target Antigens (2)
    • Replication proteins E1 and E2
      • Necessary for HPV to replicate within cells before the virus is integrated into host DNA
      • Expressed in early stage of HPV infection
      • Targets for therapeutic vaccines to treat early stages of disease such as low-grade dysplasia
  • HPV Vaccine Target Antigens (3)
    • Oncoproteins E6 and E7
      • Bind tumour supressor genes (p53/pRB) which are involved in malignant transformation / continue tumour growth
      • Expressed in the later stage of disease
      • Targets for therapeutic vaccines to treat later stages of disease
  • HPV Vaccines
    • Prophylactic Vaccines
      • Before HPV exposure
      • Antibody-mediated immunity at genital mucosal surface
      • Inactivate HPV before the virus infects the host cells
      • Takes many years to make impact on the prevalence of cervical cancer
    • Therapeutic Vaccines
      • Already exposed to HPV
      • Cell-mediate immunity at the genital mucosal surface
      • Adjunct to standard therapies
        • Prevent progression of low-grade lesions
        • Induce regression of existing lesions
        • Control metastasis
        • Prevent recurrence
  • Ideal HPV Vaccine
    • Safe and effective
    • Both prophylactic and therapeutic
      • Stimulating cell-mediated immunity to eliminate lesions when neutralizing antibodies fail to block all of the virus
      • Distributed to young women whether or not that are infected with HPV
    • Single inoculation with long-term protection
    • Cheap and easy to handle and administer
  • Vaccine Types
    • Virus-like particles (VLPs)
    • Recombinant live vector vaccine
    • Protein and peptide vaccines
    • “ Naked” DNA vaccines
    • Edible vaccines
  • Virus-Like Particles (VLPs) - 1
    • Capsid proteins L1 and L2 will self-assemble into virus-like particles (VLPs) when expressed in cells – Empty viral capsids
    • VLPs resembles native HPV particles and include the conformational epitopes that induce virus-neutralizing antibodies
    • The immune system perceives VLPs as infectious (indeed they are not since they do not include viral DNA) and induce the immune response
  • Virus-Like Particles (VLPs) - 2
    • Immune response targets the capsid proteins (at the time of viral entry), therefore ideal for prophylactic vaccine
    Vaccination No Vaccination
  • Selection of HPV Types in Vaccine Development
    • HPV type 16 and 18 present in
      • ~70% of Ca cervix cases
      • ~50 % HGSIL cases
      • ~14-25% LGSIL cases
      • Provides an estimate of the potential impact of a vaccine against HPV-16 and HPV-18
    • Quadrivalent vaccine also include HPV 6/11 to prevent genital warts
      • HPV 6/11 account for 90% of genital warts
      • Clinically apparent in 1% of sexually active US adult population
      • Estimated lifetime risk of genital warts ~10%
  • Selection of Trial Endpoints
    • Although prevention of cancer is the final endpoint for the success of a prophylactic vaccine
    • Studies to allow patients to develop cancers as endpoint are unethical
    • Surrogate endpoints are precancerous lesions (CIN, AIS, VAIN, VIN)
  • Multicenter Randomised Double Blind Controlled (Phase II) Trials Monovalent A Controlled Trial of a Human Papillomavirus Type 16 Vaccine (Nov 2002, NEJM) Median FU 17.4 mths Bivalent Efficacy of a Bivalent L1 Virus-Like Particle Vaccine in Prevention of Infection with HPV Type 16 and 18 in Young Women: A Randomised Controlled Trial (Nov 2004, Lancet) Up to 27 mths Quadrivalent Prophylactic Quadrivalent HPV (Types 6,11,16 and 18) L1 Virus-Like Particle Vaccine in Young Women: A Randomised Double-Blind Placebo-Controlled Multicenter Phase II Efficacy Trial (May 2005, Lancet Oncology) 36 mths Monovalent Efficacy of Human Papillomavirus-16 Vaccine to prevent Cervical Intraepithelial Neoplasia (Jan 2006, Obstetrics & Gynecology) 48 mths Bivalent Sustained efficacy up to 4.5 years of a Bivalent L1 virus-like particle vaccine against human papillomavirus Types 16 and 18 : follow-up from a randomised control trial (15 April 2006, Lancet) 4.5 years Quadrivalent High Sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up (Nov 2006, British Journal of Cancer) 5 years
  • Multicenter Randomised Double Blind Controlled (Phase III) Trials FUTURE I/II Trials: Females United to Unilaterally Reduce Endo/Ectocervical Disease Quadrivalent (Gardasil) Quadrivalent Vaccine against Human Papillomavirus to Prevent Anogenital Diseases (May 2007, NEJM) (FUTURE I Trial) N=5455 Average 3 yrs Efficacy of a quadrivalent prophylactic human papillomavirus (types 6,11,16 and 18) L1 virus-like particle vaccine against high-grade vulval and vaginal lesions: a combined analysis of 3 randomised clinical trials (May 2007, The Lancet) N=18174 Mean FU 3 yrs Quadrivalent (Gardasil) Quadrivalent Vaccine against Human Papillomavirus to Prevent High-Grade Cervical Lesions (May 2007, NEJM) (FUTURE II Trial) N=12167 Average 3 yrs Efficacy of prophylactic human papillomavirus L1 virus-like particle vaccine on risk of cervical intraepithelial neoplasia grade 2, grade 3 and adenocarcinoma in situ: a combined analysis of four randomised clinical trials (June 2007, The Lancet) N=20583 Mean FU 3 yrs Bivalent (Cervarix) Efficacy of a prophylactic adjuvanted bivalent L1 virus-like particle types 16 and 18 in young women: an interim analysis of a phase III double-blind, randomised controled trial (June 2007) N=18644 Mean FU 14.8 mths
  • Study Design
  • Phase II / III Clinical Trials
  • Side Effects
  • Two HPV Vaccines Available
    • Gardasil (HPV 6/11/16/18) approved in many countries including HK (Oct 2006)
    • Cervarix (HPV16/18) approved in Australia (July 2007), Indonesia, Kenya and pending approval in Europe and USA etc
  • Which is better ?
    • Gardasil (0/2/6m IMI)
    • Storage 0-8 deg C
    • HPV 6/11/16/18
    • Adjuvant contained aluminum
    • Age 9-26 yrs
    • Up to 5 years
    • Efficacy 99%
      • 1 case CIN 3: HPV 58 at baseline and 5 histology samples, HPV 16 in only 1 sample
    • Cervarix (0/1/6m IMI)
    • Storage 0-8 deg C
    • HPV 16/18
    • Adjuvant AS04
      • Claimed to enhance immune response and longer duration
    • Age10-45yrs (Australia)
    • Up to 4.5 years
    • Efficacy 90.4%
      • 2 cases CIN 2+: Multiple infection with preceding cytology HPV 16/18 -ve (Efficacy 100%)
    • Cross-protection ?
      • 45 and 31
      • Pending results from a head-to-head trial to compare immunogenicity of Cervarix and Gardasil initiated in 2007
  • Phylogenetic Tree of HPV Family 11 6 35 31 16 33 18 45 Human Genital Papillomavirus Human Cutaneous Papillomavirus Genotypying of HPV is based on DNA sequences of the L1 genes
  • Cross-Protection for Bivalent Vaccine (Cervarix) No cross protection for other HPV types other than 16/18 has been approved
  • FAQ (For Gardasil)
    • When and whom to vaccinate ?
    • Vaccination for females <9yr and >26 yrs ?
    • Vaccination in sexually active females
    • Prior HPV testing before vaccination
    • Past history of abnormal pap smear / histology ?
    • History of genital warts
    • Antibody testing before vaccination
    • Will a booster be required ?
    • Vaccination in pregnancy / during lactation
    • Duration of protection
    • Interrupted schedules / Incorrectly vaccinated individuals
    • Simultaneous administration of other vaccines
    • Immunocompromised patients
    • Precautions / Contraindications
    • Any therapeutic effect ?
    • Role of cervical screening ?
    • Other ways to prevent HPV infection
    • Vaccination in males ?
    • Social acceptance
  • When and Whom to Vaccinate
    • Licensed for use in 9-26 yr females
      • Age 16-26:
        • Based on phase II/III studies conducted among females aged 16-26 yrs
      • Age 9-15:
        • Based on immunological studies
        • Not inferior to 16-26yrs
      • Recommendation at age 11-12:
        • Before sexual exposure
          • US: 3.7% females sexually active before age 13
          • HK: 4.9% before age 15
        • High probability of HPV acquisition within several yrs of sexual exposure
        • Immune system “ages” after puberty
          • Antibody level after vaccination 9-10y > 13-15y > 16-23y
        • Incorporate into adolescent vaccination program
  • Vaccination for females <9yrs and > 26 yrs
    • Not licensed for use in these age range
    • Protocol 019 (FUTURE III)
      • In 3870 24-45yr women followed for 3 years
      • Primary endpoint:
        • Persistent HPV 16/18 infection and related disease
        • Efficacy against HPV 16/18-related CIN 2/3 and AIS
    • Off-label use: Counseling on limitations and based on clinical judgment
    • No studies are under way among children aged <9 years
  • Vaccination in Sexually Active Females
    • May also benefit from the vaccine
      • May have less benefit since they may have already been infected
      • Unlikely that they acquired all 4 types
      • Even if the patient has been infected, vaccination would provide protection against infection with HPV vaccine types not already acquired
  • Prior HPV Testing before Vaccination
    • No indication for prior HPV testing:
      • Specific HPV testing not performed routinely in clinical setting
        • Although Hybrid Capture 2 is available to test for high-risk HPV (16/18/31/33/35/39/45/51/52/56/58/59/68)
        • Does not identify specific HPV types
      • Unlikely that the women having all 4 HPV types (0.1%)
            • Positive to >= 1 types 23.7%
            • Positive to >= 2 types 6%
            • Positive to >= 3 types 1.1%
            • Positive to >= 4 types 0.1%
        • Even if the patient has been infected, vaccination would provide protection against infection with HPV vaccine types not already acquired
      • HPV infection mostly transient in young women and a positive HC 2 test may cause confusion and unnecessary anxiety
  • Prior HPV Testing before Vaccination
    • In the combined analysis of previous studies
      • Analysis of Intent-To-Treat subset :
        • Received at least 1 dose of vaccine (Protocol violation)
        • Any follow-up 1 month after the first dose
        • Even if pap smear abnormal on day 1
        • Regardless of initial PCR or serology for HPV (Overall 27% of the study population at baseline had evidence of infection with a vaccine HPV type)
        • i.e. Presumed HPV status unknown / no prior HPV testing before vaccination / Regardless of pap smears results (General Population)
      • Prevention of vaccine-related (6/11/16/18) lesions:
        • CIN2/3/AIS – 39% - 46.4%
        • VAIN 2/3 and VIN 2/3 – 69.1%
        • Genital warts – 68.5%
  • Past history of Abnormal Pap Smears / Histology
    • No contraindication for vaccination:
      • Females with equivocal / abnormal pap smears could be infected with any HPV types (high/low-risk)
        • Might not be infected with any of the 4 vaccine-types (6/11/16/18)
        • Unlikely to have infected all 4 types (0.1%)
        • Vaccination would protect them against infection with HPV vaccine types not already acquired
      • With increasing severity of pap smear (such as HGSIL)
        • Likelihood of infection with HPV 16/18 increases
        • Benefit of vaccine wound decrease
  • History of Genital Warts
    • No contraindication
      • Most often HPV 6 or HPV 11
      • But might not have infection with both types or infection with HPV 16 or HPV 18
      • Vaccination would protect them against infection with HPV vaccine types not already acquired
  • Antibody Testing before Vaccination
    • No indication for prior antibody testing:
      • Not all naturally infected individuals have antibodies
        • Only 54%-69% with incident HPV 6/16/18 seroconvert
      • Serological assays are only available in research settings and only being done by the manufacturer
        • Key laboratory reagents are not standardized
      • No gold standard for setting a threshold for a positive result
  • Decision to Vaccinate should NOT be based on Pap testing, HPV DNA or HPV serologic testing
  • Booster
    • Not recommended at this moment
      • High efficacy for preventing anogenital lesions through 5 years follow-up
      • High seropositivity remained at 36 months:
            • HPV 6 94%
            • HPV 11 96%
            • HPV 16 100%
            • HPV 18 76%
      • No evidence of waning efficacy among seronegative individuals
      • Demonstration of
      • immune memory
      • when a challenge
      • dose was given
      • at 5 yrs
    HPV 6 HPV 11 HPV 16 HPV 18
  • Vaccination in Pregnancy
    • Not recommended for use during pregnancy (Category B)
      • Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women / Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester
    • Not been causally associated with adverse outcome
  • Vaccination in Pregnancy
    • Vaccine group 1396/10418 (13.4%) vs Placebo group 1436/9120 (15.7%)
      • No difference in live birth, difficulty with delivery, spontaneous abortion, late fetal deaths
      • No difference in congenital abnormality (vaccine 25 VS placebo 22)
    Vaccination within 30 days of conception Vaccination more than 30 days of conception Vaccine Placebo Vaccine Placebo Spontaneous Abortion 19/112 26/115 266/1198 283/1218 Congenital Abnormality 5 0 20 22
  • Vaccination in Pregnancy
    • If a women is found to be pregnant after initiating the vaccination series:
      • The reminder of the dose(s) should be delayed until after delivery
      • No intervention is needed (TOP not indicated)
  • Vaccination During Lactation
    • No contraindication
      • Serious adverse event:
      • None were considered vaccine related
    Vaccine Placebo 17/500 (3.4%) 9/495 (1.8%) 12 Respiratory infection 5 Gastroenteritis
  • Duration of Protection
    • Data available for up to 5 years and exact duration depends on on-going trials
      • Phase III trials up to 3 years
      • A subset 241 participants still demonstrated 100% efficacy up to 5 years
      • Women in the Nordic countries will be followed for at least 14 years and serological testing will be obtained at 5 and 10 years
  • Interrupted Schedules (0/2m/6m)
    • Does not need to be restarted
      • Interrupted after 1 st dose:
        • Second dose to be given as soon as possible and the 2 nd and 3 rd dose be separated by at least 12 weeks
      • Interrupted after 2 nd dose:
        • Third dose to be given as soon as possible
  • Incorrectly Vaccinated Individuals (0/2m/6m)
    • Studies:
      • Interval between 1 st and 2 nd dose
        • Ranged from 6-12 weeks
      • Interval between 2 nd and 3 rd dose
        • Ranged from 12-23 weeks
      • Variation in interval did not diminish the antibody titre after vaccination
    • Minimum intervals:
      • Between 1 st and 2 nd dose: 4 weeks
      • Between 2 nd and 3 rd dose: 12 weeks
    • Inadequate doses/shorter than recommended dosing interval should be readministered
  • Simultaneous Administration of Other Vaccines
    • No contraindication:
      • Can be given with other age appropriate vaccine
      • Not live vaccine with no components that adversely impact safety or efficacy of other vaccination
  • Immunocompromised Patients
    • No contraindication
      • Non-infectious vaccine
      • Immune response or vaccine efficacy might be lower
  • Precautions / Contraindications
    • Can be given with minor illness such as diarrhoea or mild URTI
    • Withhold in persons with moderate or severe acute illness
    • Manufacturing process for GARDASIL is free of egg or egg derivatives. Therefore, GARDASIL can be used in subjects with egg allergy
    • Contraindicated with history of allergy to yeast or to any known vaccine component
  • Any Therapeutic Effect ?
    • No therapeutic effect on existing infection / precancerous lesions / genital warts demonstrated
    • However, among subcohort of women:
      • HPV 16 DNA +ve / seronegative at enrollement less likely to develop HPV 16 related CIN 2/3 than those received placebo
      • No such benefit if they were HPV 16 DNA +ve and seropositive at enrollment
      • Vaccination may have some benefit in recent infection or in the early stage of disease (Hypothesis only)
    • Sub-analysis in 1,565 women who were infected with HPV at the time of study enrollment
      • 28 percent reduction in the rate of progression to CIN 2 or worse
      • Not statistically significant
  • Role of Cervical Screening Program
    • Even if an ideal vaccine is developed, reduction of cervical cancer would not become apparent for at least a decade
    • Decline in abnormal pap smears, especially in high risk groups, may become evident within months
  • Role of Cervical Screening Program
    • Pap smear screening programs remain vital
      • Millions have already been exposed to HPV
        • Multivalent vaccine may protect them from other HPV types (immunological interference)
      • Unless a multivalent vaccine can prevent every type of high-risk HPV, a proportion of women will continue to develop cervical cancer
      • Certain cervical cancers may not be associated with HPV
      • Some women may not respond immunologically to the vaccine
        • Efficacy in immunocompromised patients (HIV, organ transplant) unclear
      • Vaccine coverage will not be 100% especially in under-developed and developing countries
  • Role of Cervical Screening Program
    • Need to continue Pap smear screening even after vaccination
    • Screening program may evolved from cytopathology basis to DNA basis
    • Need modification of screening recommendations when more long term data is available
      • Safety and cost-effectiveness to lengthen the screening interval
    • Providers should educate women about the importance of cervical cancer screening
  • Other Ways to Prevent HPV Infection
    • Avoid potential cofactors involved in HPV carcinogenesis:
      • Stop smoking
      • Prevent Co-infection with other STDs (Chlamydia and Herpes)
    • Use of Condom
    • Decrease the number of sexual partners
  • Vaccination in Males
    • Immunological studies showed immune response equally well among adolescent boys and girls
    • Theoretically prevents Genital warts / Anal cancer in males
    • Important transmission vector
      • Protect females from HPV 16 and 18 infection by herd immunity
    • Not licensed for use yet
    • Protocol 020 to evaluate young men
      • 3870 men in 16-26 year old men
      • Endpoints: HPV 6/11/16/18 related external genital lesions
      • HPV 6/11/16/18 infection
      • HPV 16/18 AIN (anal cancer)
  • Social Acceptance
    • Stigmata of STD
      • Unwilling to discuss about sexuality / STD to children
      • Concern about riskier sexual behaviors after vaccination
      • Over 80% of respondents indicated that they would get or let their daughters get vaccinated against cervical cancer
      • Over 95% of respondents would like to know more about the new cervical cancer vaccine
  • Conclusion
    • HPV Vaccines have high efficacy in preventing vaccine-related anogenital diseases
    • On-going studies to establish its duration of protection and impact on general health / cervical cancer
    • Pap smear screening is still the most important and useful test to prevent cervical cancer
  • Thank You