HPV Vaccination, Cerviocal Cancer : Do we need it for Prevention of cervical cancer & other HPV related diseasesm, Presentation Outlines Cervical cancer disease burden Prevention with HPV vaccination Vaccination of sexually active women Opportunity of Postpartum HPV vaccination Importance of genital warts prevention Real world effectiveness data Safety of HPV vaccine

1. HPV VACCINATION : Do we need it
for Prevention of cervical cancer &
other HPV related diseases
HPV
DR. SHARDA JAIN
CHAIRMAN & FOUNDER
ISO 9001:2008
ISO 14001:2004 (EMS)
…..Caring hearts, healing hands
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25/08/2015

2. Presentation Outlines
 Cervical cancer disease burden
 Prevention with HPV vaccination
 Vaccination of sexually active women
 Opportunity of Postpartum HPV vaccination
 Importance of genital warts prevention
 Real world effectiveness data
 Safety of HPV vaccine

3. 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%
Cervical cancer: Disease Burden
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]

4. Years of Life Lost (YLL)

5. An Airbus-320 full of WOMEN crashing every day in India
Deaths Due to CaCx - Just Think !

6. HPV 16
HPV 18
HPV 6
HPV 11
Cancer causing Types
High risk group-16,18,
31,33,45,52,58
Non-cancer causing types
Low risk group- 6,11.
• >75% of Cervical Cancer5,6
• >50% of Vaginal & Vulvar Cancer5
90% of Anogenital warts5
HPV is a necessary cause of cervical cancer – 99.7%4
HPV
1.Schiffman M, Castle PE. Arch Pathol Lab Med. 2003;127:930–934. 2. Wiley DJ, Douglas J, Beutner K, et al. Clin Infect Dis. 2002;35(suppl 2):S210–S224. 3. Muñoz N, Bosch FX, Castellsagué X, et al. Int J
Cancer. 2004;111:278–285. Reprinted from J Virol. 1994;68:4503–4505 with permission from the American Society for Microbiology Journals Department. 4. Walboomers JM, Jacobs MV, Manos MM, et al. J
Pathol. 1999;189:12–19. 5. X. Castellsagué, S. de Sanjose, T. Aguado, K. S. Louie, L. Bruni, J.Muñoz, M. Diaz, K. Irwin, M. Gacic, O. Beauvais, G. Albero, E. Ferrer, S. Byrne,F. X. Bosch. HPV and Cervical
Cancer in the World. 2007 Report. WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre). Available at: www.who.int/hpvcentre6. Bhatla N et al.Vaccine (2008;26; 2811-17
Human Papillomavirus (HPV)
Need for multivalent HPV vaccine for broader HPV protection

7. 1. Forman D et al. Vaccine 30S (2012) F12– F23; 2. Lacey CJ et al (2006). Vaccine, 24 (Suppl 3), S35–S41.
THE CAUSE
HPV infection is a necessary cause of cervical cancer and is
linked to several other anogenital diseases
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
HPV Causes More Than Cervical Cancer

8. HPV Vaccination: The Basis of Cancer Control
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

9. Cervical Cancer Screening Practices in India
Estimated coverage of cervical cancer screening in India, by age & study
(1) WHO Household Surveys with geographical information system (GIS) multistage cluster sampling. Screening coverage among women aged 18-69.
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]

10. WHY VACCINATION ?
• HPV vaccines are highly effective at preventing the infection
of susceptible women with the HPV types covered by the
vaccine.
• HPV vaccine should be given to females before they reach an
age when the risk of HPV infection increases and they are at
subsequent risk of cervical cancer.
• HPV vaccine can be given to all female between 9 to 45 years
of age group.
• HPV vaccine is given as 3 doses over a period of 6 months.
The ‘Green Book’ chapter on Human papillomavirus (HPV)
Gardasil : Quadrivalent
Cervix : Bivalent
Nonovalent (2016)

11. Rationale for Vaccination
Natural Infection – Weak AB response
Vaccination - High AB Response
Higher AB level at
cervical epithelium
prevents HPV infection

12. GARDASIL®: The Only Quadrivalent
HPV Vaccine1
• HPV types 6, 11, 16, 18
• Manufactured in Saccharomyces
cerevisiae
• Amorphous aluminum
hydroxyphosphate sulfate (AAHS)
adjuvant – 225 μg per dose
• 0-, 2-, 6-month dosing regimen
• Does not contain viral DNA and
therefore not infectious
1. Worldwide Product Circular. GARDASIL® [Quadrivalent Human Papillomavirus
(Types 6, 11, 16, 18) Recombinant Vaccine]; WPC-GRD-I-122008.

13. 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
√

14. GARDASIL® : Nordic Cancer Registry Extension Evaluation of Long-
Term Efficacy of Vaccination
• Nordic European countries have
organized mass screening programs.
– Compulsory reporting of Paps, biopsies,
CIN/cancer
• By enrolling phase III studies in the
region, we can evaluate:
– Duration of effectiveness
– Data for use in assessing interaction of
vaccination with cervical screening
programs
– Long-term safety
Denmark
Norway
Iceland
Sweden
CIN = cervical intraepithelial neoplasia.

15. Data on File
a FUTURE= Females United to Unilaterally Reduce Endo/Ectocervical Disease
Registry-Based Follow-Up
Vaccination
Reports
6 years 8 years 10 years
US FDA
Approval
5 years 7 years3 years
2003 2004 2005 2006 2007 2008 20132010 2011 20122009
3.5 years
FUTUREa II Study
Total Duration
Time since
approval
Report of
6-yr F/U
Follow-Up Through Nordic Registries Provides a
Sentinel Cohort (vaccinated at the start of study)

16. 0 0 0
100 % 100 % 100 %
0
20
40
60
80
100
Zero number
of cases
Vaccine
Effectiveness
Vaccine
Effectiveness
Vaccine
Effectiveness
(N=1,080) (N=921) (N=1.032)
HPV 16/18-Related
CIN 2 or Worse
HPV 16-Related CIN
2 or Worse
HPV 18-Related CIN
2 or Worse
Zero number
of cases
Zero number
of cases
Vaccine effectiveness measures the relative reduction of the disease incidence in vaccine recipients compared to the baseline incidence rate of 0.0287 per 100 person-years established from the incidence rate in an
unvaccinated cohort and under the assumption vaccine efficacy is 90%.
Per Protocol Efficacy Population
Percentage
Data on File
Effectiveness Against HPV 16/18-Related CIN 2 or Worse
(8 years registries based f/u data from Nordic countries)
Nygard, M., Long-term immunogenicity, safety and effectiveness of Gardasil in the Nordic countries Obstetrics & Gynaecology Forum;Aug2013, Vol. 23 Issue 3, p36

17. 0 0 0 0 0
0
20
40
60
80
100 Vaccineeffectiveness
(N=1,080)
Vaccineeffectiveness
Vaccineeffectiveness
Vaccineeffectiveness
Vaccineeffectiveness
Zero number
of cases
Zero number
of cases
Zero number
of cases
Zero number
of cases
Zero number
of cases
(N=1,080) (N=1,080) (N=1,080) (N=1,080)
CIN 2 CIN 3 CIN 3 + AIS CC
Vaccine effectiveness measures the relative reduction of the disease incidence in vaccine recipients compared to the baseline incidence rate of 0.0287 per 100 person-years established from the incidence rate in an
unvaccinated cohort and under the assumption vaccine efficacy is 90%.
Percentage
Per Protocol Efficacy Population
100 % 100 % 100 % 100 % 100 %
Data on File
Effectiveness by Lesion Type
(8 years registries based f/u data from Nordic countries)
Nygard, M., Long-term immunogenicity, safety and effectiveness of Gardasil in the Nordic countries Obstetrics & Gynaecology Forum;Aug2013, Vol. 23 Issue 3, p36

18. Is it worth vaccinating sexually
active women

19. 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

20. 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.

21. 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

22. Opportunity of HPV vaccination
during postpartum period

23. 23
– Primiparous women aged between 15 and 24 years, living
in the metropolitan area of São Paulo for at least 6
months, and gave birth at this hospital after more than 32
weeks of gestation, were enrolled at their postnatal visit,
from June 2006 to February 2007.
– Exclusion criteria: non-Brazilian, inability or refusal to give
informed consent, or immunodeficiency (including
AIDS/HIV infection checked in medical records).
– Women were recruited to take part in the study during the
postdelivery follow-up period in the hospital.
J Epidemiol Community Health 2010;64:610-615

24. 24
• After the first dose of vaccine,
– 97.2% of women felt it was worthwhile to receive the vaccine,
– whereas 98.6% said that administration was convenient.
• When asked, 50.4% of participants said they would not have
asked to be vaccinated if they were not part of the study.
• Among those vaccinated,
– 99.3% were happy they participated in the study and
– 97.9% would have recommended the vaccine to a friend
• Despite the acceptability of this strategy, only 30.7% of
enrolled patients completed the three-vaccine series
Wright, Govindappagari, Pawar et al, Acceptance and Compliance With Postpartum Human Papillomavirus Vaccination, Obstet Gynecol 2012;120:771–82

26. How importance is prevention of
other HPV diseases e.g.
Genital Wart (GW)

27. PREVALENCE AND PATIENT EXPERIENCE WITH
CONDYLOMATA ACUMINATA (GENITAL WARTS) IN INDIA
Khopkar U et al. Poster presented at AOGIN Hong Kong 2012
PercentofGW
Estimates are adjusted for by specialty type
Females (95% CI) Males (95% CI)
18-24 years 0.69 (0.49; 0.89) 1.25 (0.95; 1.55)
25-29 years 1.36 (1.07; 1.65) 1.60 (1.38; 1.82)
30-34 years 1.16 (0.82; 1.50) 1.76 (1.23; 2.28)
35-39 years 1.04 (0.67; 1.41) 1.63 (1.09; 2.17)
40-44 years 1.04 (0.70; 1.38) 0.90 (0.70; 1.10)
45-49 years 0.88 (0.52; 1.24) 0.55 (0.27; 0.83)
50-54 years 0.93 (0.52; 1.34) 0.46 (0.31; 0.61)
> 54 years 0.31 (0.16; 0.46) 0.84 (0.32; 1.36)
Overall 0.99 (0.88; 1.10) 1.22 (1.12; 1.33)
Both males and females have shown significantly higher psychosocial
impact than those without GW diseases

28. Genital Warts and Risk of Cancer: A Danish Study of Nearly
50000 Patients With Genital Warts
Blomberg M et al. J Infect Dis. 2012 May 15;205(10):1544-53.
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 Associated
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
Diagnosis of GW was
strongly related to anal,
vulvar, vaginal, cervical &
sub sites of HN cancer with
confirmed HPV association.

29. Genital Warts and Risk of Cancer: A Danish Study of
Nearly 50000 Patients With Genital Warts
Blomberg M et al. J Infect Dis. 2012 May 15;205(10):1544-53.
Standardized Incidence Ratios (SIRs) of Cancer among women (n = 33,422) diagnosed of GW in
Denmark during 1978–2009,
The risks in anal cancer
remained elevated for >10
years following GW
diagnosis.
9.7
14.5
9.8
6.2
0
2
4
6
8
10
12
14
16
< 1 Yr 1-4 Yr 5-9 Yr ≥10 yr
StandardizedIncidenceRatios(SIRs)
Follow up time
CI: .1-54.0 CI: 5.8-29.8 CI: 3.9-20.1 CI: 3.6-9.7
According to Follow-up time by cancer site-Anus

30. Real world effectiveness of
QHPV vaccine

31. Impact of HPV Vaccine in Public Vaccination Programs: Selected
Reports as of April 20131–21
qHPV=quadrivalent human papillomavirus. Please see corresponding slide note for references.
Markowitz. IPV 2012.
2006–2007 Dec ‘09 Jul ‘11Jan ‘11 Dec ‘11 May ‘12Jun ‘11 Jul ‘12 Jan ‘13Dec ‘12Oct ‘12
Introduction of
qHPV vaccine
Oliphant et al.
NZ Med J. 2011.
Bauer et al. Am J
Pub Health.
2012.
Wikström et al.
EUROGIN 2012.
Mikolajczyk et al.
Sex Transm Dis. 2013.
Baandrup et
al. Sex
Transm Dis.
2013.
Fairley et al. Sex
Transm Infect.
2009; Donovan
et al. Lancet
Infect Dis. 2011. Kliewer et al. IPV 2012.
Kjaer et al. IPV 2012.
Brotherton et al.
Lancet. 2011.
Van Tielen;
Weyers et al.
EUROGIN 2012.
Leval et al.
J Infect Dis. 2012.
Ali et al. IUSTI
2012.
Read et al. Sex
Transm Infect. 2011.
Powell et al.
Vaccine. 2012.
Tabrizi et al.
J Infect Dis.
2012.
2012
Sep ‘12 Feb ‘13
Leval et al.
J Natl Cancer
Inst. 2013.
Mar ‘13
Ali et al.
BMJ 2013
Apr ‘13
Ali et al.
BMC Infect Dis
2013.

32. The incidence of high grade cervical abnormalities has decreased
following the qHPV programme
1. Reprinted from The Lancet, 377, Brotherton JM et al, Early effect of HPV vaccination programme on cervical abnormalities in Victoria, Australia: an ecological study, 2085–2092,
Copyright (2011), with permission from Elsevier.
Vaccination program begins
IMPACT1
“With data from a
state-based cervical
screening register, we have
shown a
decrease in high-grade
cervical abnormalities in
young women
after the implementation of
the vaccination programme”.
Using data from the Victorian Cervical Cytology Registry between 2003 and 2009, the incidence of histopathologically defined high-grade cervical abnormalities (HGAs, lesions coded as
cervical intraepithelial neoplasia of grade 2 or worse or adenocarcinoma in situ; primary outcome) and low-grade cytological abnormalities (LGAs) was compared in five age groups before (Jan
1, 2003, to March 31, 2007) and after (April 1, 2007, to Dec 31, 2009) the vaccination programme began. Green dots represent the number of new diagnoses within a 3-month period per 100
women tested. HGA = high-grade cervical abnormalities; qHPV = quadrivalent human papillomavirus.
Incidence of high grade abnormalities among girls < 18 yrs 1
Australian experience: Real World Effectiveness of QHPV Vaccine

33. The prevalence of vaccine-preventable HPV types has decreased
following the qHPV vaccination programme
1. Tabrizi S et al. The Journal of Infectious Diseases 2012;206:1645–51
Differences in HPV genoprevalence between pre-vaccine and
post-vaccine populations 1, *
IMPACT1
“……we have shown that a
substantial and statistically
significant decrease in the
prevalence of vaccine-preventable
HPV genotype infections has
occurred following implementation
of Australia’s national HPV
vaccination program”.
* P < 0.05 for differences in percentages between groups
This study used a repeat cross-sectional design to compare HPV prevalence in 2 samples of women recruited from sentinel clinical sites. The first or “pre–vaccine implementation” sample
was made up of women aged 18–24 years (at the time of recruitment) who were recruited from participating family planning clinics (FPCs) for Papanicolaou screening during the
recruitment period of 2005–2007 and had participated in the Women, Human papillomavirus prevalence, Indigenous, Non-Indigenous, Urban, Rural Study (WHINURS) study. The second or
“post–vaccine implementation” sample comprised women aged 18–24 years who had attended FPCs in the same cities during the recruitment period 2010–2011 for Papanicolaou
screening; qHPV = quadrivalent human papillomavirus.
28.7%
6.7%
Australian experience: Real World Effectiveness of QHPV Vaccine

34. 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
Post licensure: Health authorities reaffirm the positive safety profile of
Gardasil®
US CDC & other leading health organizations closely monitor the safety of GARDASIL,
as they do with other vaccines

35. 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

36. 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 forthe 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

37. Summary
• HPV infection is more than cervical cancer!
• There is an increasing evidence strongly
linking HPV DNA with cancers of anus, vulva,
vagina, penis &
sub sites of HEAD & NECK CANCER
• Genital Warts has confirmed HPV
association.

38. 38
NOW !!!

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