5. CERVICAL CANCER DISEASE BURDEN IN INDIA
Bruni L, Barrionuevo-Rosas L, Albero G, Aldea M, Serrano B, Valencia S, Brotons M, Mena M, Cosano R, Muñoz J, Bosch FX, de Sanjosé S,
Castellsagué X. ICO Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in India.
Summary Report 2015-12-23. [Accessed on 2016-04-20 from http://hpvcentre.net/statistics/reports/IND.pdf]
2nd Common cause of
female cancer
2nd
Most common female
cancer in women aged 15-44
years
• India has a population of 436.76 million
women aged 15 years and older who
are at risk of developing cervical cancer.
6. India ~1,22,844
Total world ~ 5,27,624
India ~23% of new
Cervical Cancer cases in world
India ~ 67,477
Total world ~ 2,65,653
India ~23%
Rest of World - 77%
India ~25% of deaths
due to Cervical Cancer in world
Rest of World - 73%
India - 27%
India accounts for ~ 1/4th of Cervical
cases and deaths worldwide
Incidence Mortality
India ~25%
Rest of World - 75%
2. Bruni L, Barrionuevo-Rosas L, Serrano B, Brotons M, Cosano R, Muñoz J, Bosch FX, de Sanjosé S, Castellsagué X. ICO Information Centre on HPV and
Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in India. Summary Report 2014-01-31. [Accessed on 11th Feb 14]
7. 7
67,477
Deaths
Annually
Approx. 185 women die every day
A women is dies every 8 minutes
Approx. 8 women die every hour
CERVICAL CANCER MORTALITY IN INDIA
Bruni L, Barrionuevo-Rosas L, Albero G, Aldea M, Serrano B, Valencia S, Brotons M, Mena M, Cosano R, Muñoz J, Bosch FX, de Sanjosé S,
Castellsagué X. ICO Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in
India. Summary Report 2015-12-23. [Accessed on 2016-04-20 from http://hpvcentre.net/statistics/reports/IND.pdf]
2nd Cause in female cancer deaths and 2nd leading
cause of cancer deaths in women aged 15-44 years
8. An Airbus-320 full of WOMEN crashing every day in India
Deaths Due to Ca Cx ..more than
Deaths due to Pregnancy !!
9. Harald zur Hausen (1936 - ) won the Noble Prize in 2008 for discovering
that a virus, human papilloma virus, causes cervical cancer.
10. HPVTHE CAUSE
HPV infection is a necessary cause of cervical cancer and is
linked to several other anogenital diseases
15/200 HPV
Cause
Cancer
11. 1. Forman D et al. Vaccine 30S (2012) F12– F23; 2. Lacey CJ et al (2006). Vaccine, 24 (Suppl 3), S35–S41.
HPV Causes More Than Cervical Cancer
Genital
Warts ~100%
70%
~100%
43%
88%
Cervical
Cancer
Vaginal
Cancer
Vulvar
Cancer
Anal
Cancer
13-56%
Orophar
yngeal
Cancer
50%
Penile
Cancer
HPV
Percent of cases attributable to HPV infection 1,2
12. What Genders are infected by
Oncogenic HPV
• 90% of Cancers caused by Oncogenic
HPV occur in Women only.
• 2% of Cancers caused by Oncogenic
HPV occur in Men only
• 7% case Anal & Oropharangeal cancers
in both men & women
13. At what Age Genital HPV
Infection detected ?
• There is no age at which all boys & girls
are uninfected with oncogenic HPV
types
• Half of the new cases annually are
coming from Adolescents
• In Adolescents
prevalence peaks at 60 --80% in young women between
second & third decade due to onset of sexual exploration
• 15% infections not associated with penetrative sex
14. Women Remains at Risk for Acquiring
HPV Infection Throughout Their
Lifetimes
15. Cervical Cancer and HPV infection
• Human papillomavirus (HPV) infection is now a
well-established cause of cervical cancer. HPV
causes virtually 100% of cervical cancer cases
• There is growing evidence of HPV being a relevant
factor in other anogenital cancers (anus, vulva,
vagina and penis) and head and neck cancers.
• HPV is also responsible for other diseases such as
recurrent juvenile respiratory papillomatosis and
genital warts
Bruni L, Barrionuevo-Rosas L, Albero G, Aldea M, Serrano B, Valencia S, Brotons M, Mena M, Cosano R, Muñoz J, Bosch FX, de Sanjosé S, Castellsagué X.
ICO Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in India. Summary Report 2015-12-
23. [Accessed on 2016-04-20 from http://hpvcentre.net/statistics/reports/IND.pdf]
16. CERVICAL CANCER & HPV TYPES
• HPV types 16 and 18 are responsible for about 70% of all
cervical cancer cases worldwide. After HPV16/18, the six
most common cervical cancer causing HPV types are 31,
33, 35, 45, 52 and 58
• In India 82.7% of invasive cervical cancers are attributed
to HPVs 16 or 18.
• In India about 5.0% of women in the general population
are estimated to harbor cervical HPV-16/18 infection at
a given time
• HPV types 6 and 11 are responsible for over 90% of all
anogenital warts
Bruni L, Barrionuevo-Rosas L, Albero G, Aldea M, Serrano B, Valencia S, Brotons M, Mena M, Cosano R, Muñoz J, Bosch FX, de Sanjosé S, Castellsagué X. ICO
Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in India. Summary Report 2015-12-23. [Accessed
on 2016-04-20 from http://hpvcentre.net/statistics/reports/IND.pdf]
17. *Ray K et al, Indian J Med Res 2006; 124: 559-56 - done in STD clinic
18.1%
5.8%
11% 10.5%
0
2
4
6
8
10
12
14
16
18
20
1990-93 1994-97 1998-01 2002-04
Study Period
Percentage
Genital Warts – Disease Burden: India*
THERE IS AN INCREASING TREND OF
GENITAL WARTS INCIDENCE IN INDIA
In approximately
10 years time the
incidence of GW
have increased 3
times
18. Diagnosis of GW was strongly related to Anal, Vulvar,
Vaginal, Cervical and Head & Neck cancer with confirmed
HPV association [DENMARK study ]
Standardized Incidence Ratios (SIRs) of Cancer among women (n = 33,422) diagnosed of GW in Denmark during 1978–2009
2.8
1.5
5.9
7.8
14.8
4.7 4.8
0
2
4
6
8
10
12
14
16
All HPV
related
cancers
Cervix
uteri
Vagina
Anus
Vulva
Tonsils
HPV
Associat
ed HNC
StandardizedIncidenceRatios
(SIRs)
CI: 2.4- 3.1
CI: 5.5-
9.2
CI: 2.2-12.9
CI: 5.4- 11.0
CI: 11.7-18.6
CI: 2.3-8.4
CI: 2.7-8.0
Blomberg, Friis, Munk et al, Genital Warts and Risk of Cancer: A Danish Study of Nearly 50 000 Patients With Genital Warts, JID, 2012
19. CERVICAL CANCER PREVENTION
World Health Organization, United Nations Population Fund. Preparing for the Introduction of HPV
Vaccines: Policy and Programme Guidance for Countries. Geneva, Switzerland: World Health
Organization; 2006.
Palliative
care
Cancer treatment
Secondary prevention:
Screening and
treatment
of precancers
Primary prevention:
Vaccination
20. Rationale for Vaccination
Natural Infection – Weak AB response
Vaccination - High AB Response
Higher AB level at
cervical epithelium
prevents HPV infection
21. PREVENTION STRATEGIES
SCREENING:
• Well-organised cervical screening programmes or
widespread good quality cytology can reduce cervical
cancer incidence and mortality.1
• However, competing health care priorities, insufficient
financial resources, weak health systems, and limited
numbers of trained providers have made high coverage for
cervical cancer screening in most low- and middle-income
countries difficult to achieve. 2
Vaccination:
• The introduction of HPV vaccination has considerably
reduced the burden of Cervical cancer.
1. Bruni L, Barrionuevo-Rosas L, Albero G, Aldea M, Serrano B, Valencia S, Brotons M, Mena M, Cosano R, Muñoz J, Bosch FX, de Sanjosé S, Castellsagué X. ICO
Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in India. Summary Report 2015-12-23. [Accessed
on 2016-04-20 from http://hpvcentre.net/statistics/reports/IND.pdf]; 2. WHO guidance note: comprehensive cervical cancer prevention and control: a
healthier future for girls and women. Accessed online on 20-4-2016 from http://apps.who.int/iris/bitstream/10665/78128/3/9789241505147_eng.pdf?ua=1
22. HEALTH IMPACT OF HPV VACCINATION AND
CERVICAL CANCER SCREENING IN INDIA
Impact on cancer reduction*
Diaz M, Kim JJ, Albero G et al. Health and economic impact of HPV 16 and 18 vaccination and cervical cancer screening in India. British Journal of
Cancer (2008) 99, 230 – 238
*Base case assumes 70% vaccination and screening coverage
Vaccination only
Screening only (VIA – 1x, 2x, 3x)
23. COMBINING SCREENING AND VACCINATION HAS MAXIMUM
IMPACT ON CERVICAL CANCER REDUCTION
Impact on cancer reduction*
Diaz M, Kim JJ, Albero G et al. Health and economic impact of HPV 16 and 18 vaccination and cervical cancer screening in India. British Journal of Cancer (2008)
*Base case assumes 70% vaccination and screening coverage
Vaccination only
Screening only (VIA – 1x, 2x, 3x)
Vaccination followed by screening (VIA – 1x, 2x, 3x)
Health impact of HPV vaccination followed by cervical cancer screening in India
24. CERVICAL CANCER PREVENTION in
India
World Health Organization, United Nations Population Fund. Preparing for the Introduction of HPV
Vaccines: Policy and Programme Guidance for Countries. Geneva, Switzerland: World Health
Organization; 2006.
Palliative
care
Cancer treatment
Secondary prevention:
Screening and
treatment
of precancers
Primary prevention:
Vaccination
Less than 1%C
2.6%
26. NEXT FEW SLIDES WILL FOCUS
DIFFERENT ASPECT OF
HPV VACCINATION
• Adolescence is a vulnerable age – ACE10/10
involve pediatricians
• Why to vaccinate early
• The clinical evidence
• Impact of early vaccination
• Safety
• The recommendations
27. Adolescence is a vulnerable age
IAP’s initiative
for involving pediatricians
28. ADOLESCENCE IS A VULNERABLE AGE
• IAP launched Adolescent Care
Endeavor (ACE) to drive
awareness and education on
comprehensive adolescent
CARE targeting Health, nutrition
and vaccination.2
1. http://www.who.int/topics/adolescent_health/en/
2. http://health.economictimes.indiatimes.com/news/policy/indian-academy-of-paediatrics-launches-
ace-10/10-healthcare-initiative-for-adolescents/50923836
29. ACE10/10 (Adolescent Care Endeavor)
1. http://health.economictimes.indiatimes.com/news/policy/indian-academy-of-paediatrics-launches-ace-10/10-healthcare-initiative-for-adolescents/50923836
32. Increased Risk of HPV Infection in Young Females:
Progression of the Transformation Zone
Adolescent females may have
increased susceptibility to HPV
infection, compared with adults.
During and after puberty, the
transformation zone is
particularly vulnerable to
infection and carcinogenesis.1,2
~99% of HPV-related genital cancers
arise within the transformation
zone of the cervix.1
1. Castle PE. J Low Genit Tract Dis. 2004;8:224–230.
2. 2. ACOG Committee on Adolescent Health Care. Obstet Gynecol. 2004;104:891–898.
SCJ = squamocolumnar junction.
33. Exposure to HPV at a Young Age Increases the Risk of
Cervical Lesions and Cancer in Women[1]
1
2
3
4
5
6
7
CIN Invasive Cervical Cancer
RelativeRiskEstimatesa
≤17
18–22
aMantle-Haenszel estimates adjusted for age only.
1. La Vecchia C et al. Cancer. 1986;58:935–941.
Relative risks for CIN and invasive cancer increase with decreasing age of first
sexual intercourse.
Age at First
Intercourse (Years)
(n=206) (n=327)
Reference Population: First intercourse 23 years of age or never
5 times higher risk
of Invasive cancers
34. Optimal Timing for Primary Prevention Is
Before Exposure1s
“…HPV infection is sexually transmitted
and is usually acquired within the first
few years following sexual debut.”
“Ideally, therefore, the vaccine should
be administered before sexual debut,
ie, before any risk of exposure to HPV.”
World Health Organization
1. World Health Organization, United Nations Population Fund. Preparing for the Introduction of
HPV Vaccines: Policy and Programme Guidance for Countries. World Health Organization; 2006.
36. Comparison of the Immunogenicity and Reactogenicity of a
Prophylactic QHPV Vaccine in Male and Female
Adolescents and Young Adult Women
The Bridging study: Stan L Block etal
Background
• HPV vaccine efficacy studies were not
conducted in adolescents younger than 16 years
due to legal and ethical issues regarding
evaluations of sexual activity in this population
and the relatively low rate of exposure at this
age.
Stan L. Block, Terry Nolan, Carlos Sattle et al Comparison of the Immunogenicity and Reactogenicity of a Prophylactic
Quadrivalent Human Papillomavirus (Types 6, 11, 16, and 18) L1 Virus-Like Particle Vaccine in Male and Female Adolescents
and Young Adult Women PEDIATRICS Volume 118, Number 5, November 2006
37. CONCLUSION
• Non-inferior immunogenic responses to all
4 human papillomavirus types in the
quadrivalent vaccine in young women &
girls.
• The vaccine generally was well tolerated.
Stan L. Block, Terry Nolan, Carlos Sattle et al Comparison of the Immunogenicity and Reactogenicity of a Prophylactic
Quadrivalent Human Papillomavirus (Types 6, 11, 16, and 18) L1 Virus-Like Particle Vaccine in Male and Female
Adolescents and Young Adult Women PEDIATRICS Volume 118, Number 5, November 2006
38. SAFETY and Persistent Immunogenicity of a qHPV
Vaccine in Preadolescents and Adolescents
- Keith S. Reisinger et al
OBJECTIVE:
• To evaluate the tolerability and immunogenicity
of quadrivalent vaccine in males and females
9 to 15 years of age through 18 month post
enrollment.
STUDY POPULATION:
• 1781 sexually naive children were assigned (2:1)
to qHPV vaccine or saline placebo administered
at day 1 and months 2 and 6.
Keith S. Reisinger, Stan L. Block, Eduardo Lazcano-Ponce et al Safety and Persistent Immunogenicity of a Quadrivalent
Human Papillomavirus Types 6, 11, 16, 18 L1 Virus-Like Particle Vaccine in Preadolescents and Adolescents The Pediatric
Infectious Disease Journal Volume 26, Number 3, March 2007
39. Results: Anti-HPV Responses at Month
7 (PP)
0
10
20
30
40
50
60
70
80
90
100
Anti HPV 6 Anti HPV 11 Anti HPV 16 Anti HPV 18
Girls
Boys
%ageseroconversion
99.8%
99.8%
99.8%
99.6%
99.8%
99.5%
99.8%
99.8%
Keith S. Reisinger, Stan L. Block, Eduardo Lazcano-Ponce et al Safety and Persistent Immunogenicity of a Quadrivalent
Human Papillomavirus Types 6, 11, 16, 18 L1 Virus-Like Particle Vaccine in Preadolescents and Adolescents The Pediatric
Infectious Disease Journal Volume 26, Number 3, March 2007
At month 7, seroconversion rates were 99.5% for all the 4 vaccine-HPV-types.
40. Results: Anti-HPV Responses at Month
18 (PP)
%ageseroconversion
99.8%
99.8%
99.8%
99.6%
99.8%
99.5%
99.8%
99.8%
Keith S. Reisinger, Stan L. Block, Eduardo Lazcano-Ponce et al Safety and Persistent Immunogenicity of a Quadrivalent Human Papillomavirus Types 6, 11, 16,
18 L1 Virus-Like Particle Vaccine in Preadolescents and Adolescents The Pediatric Infectious Disease Journal Volume 26, Number 3, March 2007
0
10
20
30
40
50
60
70
80
90
100
Anti HPV 6 Anti HPV 11 Anti HPV 16 Anti HPV 18
Girls
Boys99.3%
97.8%
99.2%
92.5%
99.3%
99.8%
97.9%
91.5%
At month 18, >/=91.5% of vaccine recipients were seropositive,
regardless of gender.
41. CONCLUSION
• In 9- to 15-year-old adolescents, the quadrivalent vaccine was
generally well tolerated and induced persistent anti- HPV
serologic responses in the majority of subjects for at least 12
months following completion of a three-dose regimen.
• No serious vaccine-related adverse experiences were reported.
• The vaccine durability supports universal HPV vaccination
programs in adolescents .
Keith S. Reisinger, Stan L. Block, Eduardo Lazcano-Ponce et al Safety and Persistent Immunogenicity of a Quadrivalent
Human Papillomavirus Types 6, 11, 16, 18 L1 Virus-Like Particle Vaccine in Preadolescents and Adolescents The Pediatric
Infectious Disease Journal Volume 26, Number 3, March 2007
42. Two – Dose regime of 4HPV :
Indian Perspective
Dr. Jyoti Agarwal
…..Caring hearts, healing hands
43. Long-term Study (8 yr follow-up of
Reisinger etal) of qHPV Vaccine in
preadolescents and adolescents
Daron Ferris et al
Daron Ferris, Rudiwilai Samakoses, Stan L. Block et al Long-term Study of a Quadrivalent
Human Papillomavirus Vaccine PEDIATRICS Volume 134, Number 3, September 2014
44. STUDY GROUPS
• The cohort who received HPV4 vaccine at
months 0, 2, and 6 in the base study are
referred to as the Early Vaccination Group
(EVG) (n=1179)
• The cohort who received placebo in the base
study and who later received a 3-dose
regimen of HPV4 vaccine starting at month
30 are referred to as the Catch-up Vaccination
Group (CVG) (n=482)
Daron Ferris, Rudiwilai Samakoses, Stan L. Block et al Long-term Study of a Quadrivalent Human
Papillomavirus Vaccine PEDIATRICS Volume 134, Number 3, September 2014
45. RESULTS – EFFECTIVENESS*
Early vaccination Group (EVG) Female (n=256) -
• No cases of HPV6/11/16- or 18-related disease were observed
• No observed cases of HPV6/11/16 or 18 related persistent
infection of >/=12 months duration
100% effectiveness at 8 years in EVG
Catch-up Vaccination group (CVG) female (n=126) -
• 2 cases of HPV16-related persistent infection and 4 cases of HPV
18-related persistent infection were detected.
• There was also 1 case of CIN1 related to HPV18.
Daron Ferris, Rudiwilai Samakoses, Stan L. Block et al Long-term Study of a Quadrivalent Human Papillomavirus Vaccine PEDIATRICS Volume 134, Number
September 2014
46. LONG-TERM EFFECTIVENESS OF
GARDASIL™ IN THE
NORDIC COUNTRIES
• Effectiveness and safety analyses occur ~2 years
following completion of FUTURE II and every ~2
years thereafter for 10 yrs
• Immunogenicity analyses occur after the year 5
Kjaer SK, An evaluation of the long-term effectiveness, immunogenicity and safety of the
quadrivalent vaccine in previously vaccinated women, Presented at Eurogin 2015
47. 0
0
20
40
60
80
100
Zero number
of cases
Vaccine
Effectiveness
(N=1,984)
HPV 16/18-Related CIN 2 or Worse
Per Protocol Efficacy Population (N=1984)
Longest follow up: 10 years
Effectiveness Against HPV 16/18-Related
CIN 2 or Worse
VE:100 %VaccineEffectiveness*(VE)
Percentage
LONG-TERM EFFECTIVENESS OF GARDASIL™ IN THE NORDIC COUNTRIES. Kjaer et al. Poster presented at EUROGIN 2015.
48. Long term effectiveness of Gardasil in
NORDIC COUNTRIES: Summary
• This is the longest follow-up (10 years)
effectiveness data available with Gardasil so far.
• In HPV16 & 18 naïve women aged 15-26 years
old, Gardasil has shown 100% effectiveness in
preventing HPV 16/18-Related CIN 2 or Worse,
when followed up for 10 years
LONG-TERM EFFECTIVENESS OF GARDASIL™ IN THE NORDIC COUNTRIES. Kjaer et al. Poster presented at
EUROGIN 2015.
49. SUMMARY so far on
ADOLESCENTS
• Adolescent females are at higher risk of HPV
infection
• Organization like WHO , FOGSI & IAP recommend
early HPV vaccination
• In adolescents qHPV vaccine is well tolerated
• The 8 year follow up data showed that qHPV
vaccine is safe and effective in adolescents
• 10 year follow-up after qHPV vaccination showed
100% effectiveness against HPV 16/18 related CIN2
in HPV 16 & 18 naïve women aged 15-26 years old
51. Estimated Benefit of Vaccination With
GARDASIL in Sexually Active Women
99.9% of
women will
benefit2
99.6% of
women will
benefit2
► Women who have been exposed to at least 1 but not all vaccine-
targeted HPV types will derive some benefit from vaccination.1
1. Wright TC Jr et al. Gynecol Oncol. 2008;109(2 suppl):S40-S47. 2. Data on file, MSD.
Infected with all 4 types
Infected with 3 types
Infected with 2 types
Infected with 1 typeWomen unexposed to any
vaccine-targeted type
52. aEfficacy after 3 doses in women 24–45 years of age naïve to the
relevant type at baseline.
Per-Protocol Efficacy Populationa – Primary Endpoint
Related
Cases
5510
86
56
30
0
20
40
60
80
24- to 45-Year-Olds 24- to 34-Year-Olds 35- to 45-Year-Olds
n=1910 n=1907
88.7%
Reduction
(78, 95)
91.3%
Reduction
(78.4, 97.3)
83.8%
Reduction
(57.9, 95.1)
GARDASIL® PlaceboTotal
Mean Follow-Up: 3.8 Years
GARDASIL®: Adult Women Efficacy Study
Combined Incidence of HPV 6/11/16/18-Related Persistent Infection or
Cervical/Vulvar/Vaginal Disease in Women 24–45 Years of Age1
1. Castellsagué X et al. Br J Cancer. 2011.
53. GARDASIL®: FUTURE III: Adult Women Study (LTFU)
Combined Incidence of HPV 6/11/16/18-Related CIN2 or worse in Women
24–45 Years of Agea
a Effectiveness in the early vaccination group after 3 doses in women 24–45 years of age naïve to the
relevant type at baseline in an extension study of FUTURE III trial in Columbia.
Per-Protocol Efficacy Population a – Primary Endpoint
Related
Cases
1511
29
21
7
0
30
CIN & EGL or worse CIN or worse CIN 2 or worse
GARDASIL® Expected cases
Total
Mean Follow-Up: 6.3 Years
1
20
10
una J, et al. Long-term follow-up observation of the safety, immunogenicity, and effectiveness of Gardasil™ in adult women PLoS One. 2013 Dec
31;8(12):e83431
High efficacy seen in
adult women
55. The impact of vaccination
with various
National Immunization Programs
56. Impact of qHPV Vaccine in Public Vaccination Programs:
Select Reportsa
*Study links effectiveness data to vaccination status.
aIncludes reports published in the peer-reviewed scientific literature and does not encompass reports at scientific conferences.
Please see corresponding slide notes for references.
Genital Warts
Cervical Abnormalities
HPV Prevalence
New
Zealand
Denmark
Sweden
United
States
Germany
Australia
Canada
Introduction of qHPV vaccine1–4
Fairley
Sex Trans Infect5
Ali
BMC Infect Dis13
Ali
BMJ14
Baandrup
Sex Transm Dis4
Baldur-Felskov
Cancer Causes
Control23
Baldur-Felskov
JNCI24
Bauer
Am J Public
Health10
2006 2007 2008 2009 2010 2011 2012 2013 2014
Blomberg
CID11
Brotherton
Lancet18
Chow
BMJ16
Crowe
BMJ21
Deleré
BMC Infect Dis28
Donovan
Lancet Infect
Dis7
Flagg
Am J Public
Health15
Gertig
BMC Med20
Harrison
PLOS One17
Leval
J Infect Dis9
Leval
JNCI3
Mahmud
J Clin Oncol22
Markowitz
JID26
Mikolajczyk
Sex Transm Dis12
Oliphant
NZMJ8
Powell
Vaccine19
Read
Sex Trans Infect6
Tabrizi
JID25
Tabrizi
Lancet Infect
Dis27
*
*
*
*
*
*
*
*
*
*
*
57. Why Genital Wart data is Important?
A reduction in the incidence of GWs is one of
the first markers of the effectiveness of HPV
vaccination at a population level, as they
develop over a few months, whereas
precancerous lesions and cancer usually
develop over several years.
1
1. Blomberg et al: Clinical Infectious Diseases 2013;57(7):929–34
58. Five Years Into qHPV Vaccination Program, Significant Declines in Rates
of Genital Warts in AUTRALIAN FEMALES<30 Years of Age1
aAnalyses included a total of 34,900 females.
Figure reproduced from BMJ, Ali H et al, 346, f2032, 2013, with permission from BMJ Publishing Group Ltd.
1. Ali H et al. BMJ. 2013;346:f2032.
Year
20
18
16
12
10
8
6
4
2
0
14
2004 2005 2006 2007 2008 2009 2010 2011
Prevaccine period Vaccination period
Ptrend <0.001
Ptrend <0.001
Patients(%)
–72.6%
–92.6%
qHPV vaccine introduced <21 years (n=9,405)a
21–30 years (n=15,228)
>30 years (n=10,246)
• Significant decline in proportion of females diagnosed with genital warts
at first visit seen during qHPV vaccination period, especially in those
<21 years of age.
Proportion of Australian-Born Women Diagnosed as Having Genital Warts at
First Visit, by Age Group, 2004 to 2011
59. 1. Oliphant J et al. N Z Med J. 2011;124:51–58.
New Zealand: Impact of qHPV Vaccine on
Genital Warts1
63%
reduction
%First-visitclients
withgenitalwarts
2010a
60. 0
10
20
30
40
50
60
70
80
90
100
10–13 14–16 17–19 20–22 23–26 ≥27
Vaccine Effectiveness Against Genital Warts Was Greatest in
Females Vaccinated at a Younger Age
qHPV Vaccine Effectiveness: A Swedish National Cohort Study1
aEstimated effectiveness for women 27 years of age and older was <0 (95%CI: <0–13).
Estimated Effectiveness of qHPV Vaccination on Incidence
Rates of Genital Warts, by Age Group
Age (years)
Estimatedeffectiveness(%)
• Maximum reduction in incidence decreased with increasing age.
• No reduction in incidence was seen for those ≥27 years of age.
a
Amy Leval, Eva Herweijer, Alexander Ploner et al Quadrivalent Human Papillomavirus Vaccine Effectiveness: A Swedish National Cohort Study J Natl Cancer
Vaccine effectiveness was highest in girls vaccinated before age 14 years
(effectiveness = 93%, 95% CI = 73% to 98%)
61. 0
2
4
6
8
10
12
14
16
18
20
Female 14-19 yrs 20-24 yrs
Prevaccine era (2003–
2006)
Vaccine era (2009–2012)
Prevalence of HPV After Introduction of the
Vaccination Program in the United States
4vHPVtypeprevalencepercentage
11.5%
12.1%
18.5%
4.3%
34%
64%
LE Markowitz etal - PEDIATRICS Volume 1 37, number 3 , March 2016: e2 0151968
62. Diagnosis
qHPV Vaccination Reduced the Number of Precancerous
Cervical Lesions Among Women in the USA
aIncludes cases with known vaccination and trigger Pap dates.
AIS=adenocarcinoma in situ; CIN=cervical intraepithelial neoplasia.
1. Powell SE et al. Vaccine. 2012;31:109–113.
n=5
0
10
20
30
40
50
60
70
80
90
100
Overall CIN2 CIN2/3 CIN3 AIS/AIS+CIN
Patients(%)
≥1 Dose before trigger Pap ≥1 Dose on/after trigger Pap Not vaccinated
HPV Vaccination Status and Timing, by Diagnosis
n=1,900a n=1,096a n=251a n=526a n=27a
n=441
n=380
n=1,079
n=273
n=230
n=593
n=56
n=40
n=155
n=107
n=105
n=314
n=5
n=17
• Fewer diagnoses of CIN2+ seen in vaccinated (with ≥1dose) than in unvaccinated
women.
n=5
63. CANADA: Early Benefits of qHPV Vaccination on
Cervical Dysplasia
1
• Vaccine exposure was ascertained in
grades 8 to 9 and outcomes in grades
10 to 12.
• Minimum Follow up time for
Cervical Dysplasia: 2 Years post-
Vaccination
• Baseline Cervical Dysplasia: 9.4 per
1000 female
• Outcome: Reduction in Cervical
Dysplasia 5.7 per 1000 female
1. Smith et al: PEDIATRICS Volume 135, number 5, May 2015
0
1
2
3
4
5
6
7
8
9
10
BaseLine Vaccinated
CervicalDysplasia:per1000female
Reduction
5.7 per 1000
female
Significant reduction in Cervical Dysplasia in Post - QHPV vaccination
1
65. 1. http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2009/11/news_detail_000389.jsp&mid=WC0b01ac058004d5c1 2. Centers for Disease control website. Available at:
http://www.cdc.gov/vaccinesafety/vaers/gardasil.htm- last accessed on 16.04.10. 3. RELEVE EPIDEMIOLOGIQUE HEBDOMADAIRE, No. 15, 2009, 84, http://www.who.int/wer 4. Press release Spain MINISTERIO DE
SANIDAD Y POLÍTICA SOCIAL 23.04.2009
Health authorities reaffirm the positive safety
Both Vaccine available in INDIA
US CDC & other leading health organizations closely monitor the safety of GARDASIL,
as they do with other vaccines
66. Evaluation of Safety QHPV vaccine: From clinical
studies to surveillance in real-life populations
Studied during a decade
in large clinical studies,
including
>35,000 women
from 33 countries
111 million doses
worldwide1
Collect and evaluate
reports of events
occurring
after vaccination
Ongoing short-term and
long-term studies
including over
51,000 subjects,
in coordination
with regulatory
and health authorities
Clinical studies PharmacovigilanceSurveillance
Evaluation by experts
and authorities
Regular update of and
evaluation by authorities
Regular update of and
evaluation by authorities
Published
Reassuring safety statements by the authorities
in Europe and the U.S.
Licensed in
127
countries
67. Global Vaccine Safety
Human papillomavirus vaccines safety (HPV)
Extract from report of GACVS meeting of 11-12 December 2013, published in the WHO Weekly
Epidemiological Record on 14 February 2014
69. IN INDIA, BOTH IAP AND FOGSI RECOMMEND THE
HPV VACCINE AND SCREENING
► Both are equally efficacious against cervical cancer and precancerous lesions. The quadrivalent vaccine
additionally protects against anogenital warts
► The recommended age for initiation of vaccination is 11-12 years. Catch up vaccination is permitted up to
the age of 45 years
► Experience with the HPV vaccines used in the post-licensure observational study confirms the good safety
profile reported in clinical trials
Indian Academy of Pediatrics (IAP) 1,2
Efficacy
Cohort
Safety
1. Yewale V, Choudhury P, Thacker N. IAP Immunization Committee - IAP Guidebook on Immunization 2009-2011; 2. VIPIN M VASHISHTHA, AJAY KALRA, ANURADHA BOSE, PANNA
CHOUDHURY, VIJAY N YEWALE, CP BANSAL, SAILESH G GUPTA Indian Academy of Pediatrics, Advisory Committee on Vaccines and Immunization Practices (ACVIP) , 2013; 3. Purandare CN
and Saraiya UB. Recommendations for vaccination against Human Papilloma Virus (HPV) infection for the prevention of cervical cancer. FOGSI ICOG Good Clinical Practice
Recommendations
► Both protect against HPV genotypes 16 and 18. The quadrivalent vaccine also protects against types 6 and
11 that are responsible for about 90% of genital warts
► Routine HPV vaccination is recommended for females aged 10 to 12 years. HPV vaccination may be
offered to all upto 45 years, but offers less benefit if already sexually active
Federation of Obstetric & Gynecology Societies of India (FOGSI)3
Efficacy
Cohort
70. WHO SAGE recommendations
for 9 to 14 years
• SAGE recommends that the immunological evidence
is sufficient to conclude that a
• 2-dose prime-boost schedule (given with a
minimal interval of 6 months)
was non-inferior to a
• 3-dose (prime-prime-boost, at 0, 1–2, and 6
months) schedule
for adolescent/pre-adolescent girls aged 9-14 years
71. IAP Recommendations
• Only 2 doses of either of the 2 HPV vaccines for adolescent/pre-adolescent
girls aged 9-14 years.
• For girls 15 years and older and immunocompromised individuals 3 doses are
recommended
• For 2 –dose schedule, the minimum interval between doses should be 6
months
• For 3 dose schedule, the doses can be administered at 0, 1-2 (depending on
brands) and 6 months.
VASHISHTHA et al, Indian Academy of Pediatrics (IAP) Recommended Immunization Schedule for Children Aged 0 through 18 years – India,
2014 and Updates on Immunization VOLUME 51__OCTOBER 15, 2014
72. Adolescent vaccination: Summary
• Adolescent females may have increased
susceptibility to HPV infection, compared with
adults
• Exposure to HPV at a Young Age Increases the
Risk of Cervical Lesions and Cancer
• Studies have shown that early qHPV vaccination
is effective and safe
• Population based/national HPV immunization
programs have shown significant reduction in
the HPV infection and disease burden
• Organization like WHO, FOGSI, IAP recommend
early HPV vaccination
73. QUADRIVALENT BIVALENT
HPV Types
Indicated age and
gender
Female 9-45 years old
Female 10-45 years
old
Indicated for
preventing…
Cervical cancer,
Vulvar cancer,
Vaginal cancer,
Genital warts
Cervical cancer
Important Differences
1. Villa LL, Costa RLR, Petta CA, et al. Lancet Oncol. 2005;6:671–678. 2. Harper DM, Franco EL, Wheeler C,
et al. Lancet. 2004;364:1757–1765.
2. PI of gardasil and Cervarix
6 11 16 18 16 18
74. Genital Warts2
Vulvar/ Vaginal Precancers
(Grade 1- 3)2
Cervical Cancer &
Precancers (Grade 2/ 3)1
99%
98%
100%
HPV induced lesions Protection
1. The Future II Study Group. Lancet 2007; 369:
1861–68 2.Garland SM et al. New Engl J Med.
2007;356:1928–1943.
Efficacy of Quadrivalent/ Bivalant HPV Vaccine:
BIVALANT
cervarix
√
X
√
75. Outcomes of phase III randomized controlled trials to date: per-
protocol efficacy populations
Quadrivalent HPV Vaccine Bivalent HPV Vaccine
Trial FUTURE - Females United to
Unilaterally Reduce Endo/Ectocervical
Disease (N ~ 20,000, FUTURE I & II
&Protocol 007)
PATRICIA (PApilloma TRIal
against Cancer In
young Adults) (N=18,644)
Efficacy HPV-16/18
CIN2/3
98%a (94-100) 93%a (79.9 – 98.3)
- HPV-16/18 VIN3/VaIN3 100% (83–100) Not reported
- HPV6-11/16/18
VIN1/VAIN1
100% (86–100) Not reported
EGL 99% (97–100) Not reported
Tolerability Well tolerated Well tolerated
Therapeutic efficacy None None
Efficacy in Adult women
(> 26 years )
Proven with FUTURE 3 Trials with
~ 90% efficacy (N= 3819)
Immunogenicity study
done
Lactation May be given in lactating women (SAFE) Data insufficient
Margaret Stanley, Potential mechanisms for HPV vaccine-induced long-term protection, Gynecologic Oncology 118 (2010) S2–S7
