1. Latest Update
on
CERVICAL CANCER
&
HPV- Vaccine
Dr. Sharda Jain
Director :-
Sec General : Delhi Gynae ForumLatest Update 2013

2. Cervical Cancer
• Second most frequent
cancer among
women
worldwide
• Most common cancer
among women in developing
countries
• Most frequent cause of death
from
cancer in women from
developing countries
2nd 15.3
7.8
GLOBOCAN 2008

3. • 500,000 women diagnosed per year1
• 270,000 deaths per year1
– >1 million new cases of cervical cancer each
year,
• 1 out of 4 women who die due to Cervical Cancer
in the world is an Indian3
1. Ferlay J, et al. GLOBOCAN 2002 Cancer Incidence, Mortality and Prevalence Worldwide. IARC CancerBase; Lyon, 2004;
2. Parkin DM, et al. Eur J Cancer 2001; 37(Suppl 8):S4-S66.
3. GLOBOCAN 2008

4. • Every year 134000 Indian women are diagnosed
with Cervical cancer and around 72000 die from
the disease
• Cervical cancer ranks No. 1 among cancers in
Indian women, that’s even more than Breast
Cancer
GLOBOCAN 2008 Cancer Incidence, Mortality andPrevalence India

5. Age-standardised incidence and mortality rates:
Indian women
GLOBOCAN 2008

6. > 200 women die every day
Every 7 minutes a women dies
8 women die every hour
Cervical Cancer :
India
This ‘Cause’ need to be taken up by multiple stake holders.
Cervical Cancer in India

7. Economic burden
• With 1,32,000 cases and 75-
80% in advanced stage,
bimodality treatment, the cost
will be huge
• With only forty percent
surviving, tremendous cost
involved
• Human loss, human
manpower, hospital resources
added to the cost.
• According to the National
Commission on
Macroeconomics of Health report
(2005), the per unit cost of
providing secondary care for
cervical cancer at the level of
district hospitals is 10,016.04
INR, higher than that of all other
chronic conditions with the
exception of cardiovascular
diseases.
• Due to the high number of
cervical cancer cases in the
population, it has the highest
total cost of secondary care
(100,000 INR per 100,000
population) relative to all other
cancers.
“Report of the National Commission on Macroeconomics and Health”,
NCMH, Ministry of H &FW, Government of India, August 2005.

8. The Nobel Prize in Physiology or Medicine 2008
Herold Zur Hausen
HPV is the necessary or the key cause of
cervical cancer
Cervical cancer does not and will not
develop in the absence of the
persistent
presence of HPV DNA.

9. Converted this extra-ordinary
discovery into UTILIZABLE
INVENTION BY Producing HPV
Vaccine
Awarded “Australian of the year”
award in 2006
Ian Frazer – An Australian Scientist

10. HPV causes more than cervical cancer
80+%
~40%
~100%
60-90%
~100%
Percentages represent cases atrributable to HPV infection
Cervical
Cancer1,3
Vulvar
Cancer1
Vaginal
Cancer1
Anal
Cancer1-3
Genital
Warts1,3
12-70%
Head &
Neck
Cancer3
45%
Penile
Cancer3
Braaten KP et al. Rev Obstet Gynecol. 2008;1:2–10.
Hoots BE et al. Int J Cancer. 2009;124:2375–2383.
IARC. IARC monographs on the evaluation of carcinogenic risks to humans. Human papillomaviruses. Vol 90. Lyon, France: IARC, 2007.

11. Attributable to
HPV
Site
Total
cancers
% Cases
Cervix 492,800 100 492,800
Vulva,
vagina
40,000 40* 16,000
Anus 15,900 90* 14,300
Oropharyn
x
9,600 12* 1,100
Mouth 98,400 3* 2,900
Total 527,100

12. In India 4 HPV Types: HPV 16, 18, 31 and 45 are responsible for
>90%>90% Squamous Cell Carcinoma2
>95%>95% Adenocarcinoma2
100 HPV Types Have Been Identified1
30 HPV Types are Transmitted by Genital skin to skin Contact
15 HPV Types are Oncogenic
1.Munoz N et al. N Engl J Med 2003; 348(6):518-527
2. WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre). Human Papillomavirus
and Related Cancers in India. Summary Report 2010.

13. • HPV infections are very common and up to 80% of women
will acquire an HPV infection in their lifetime5–7
• The risk of oncogenic HPV infection is high even after first
intercourse and continues throughout a woman’s sexually
active lifetime2–4
• Although new infections decrease with age, risk of their
persistence increases with age8
• The cumulative risk of acquiring cervical HPV infection in
women with only one sexual partner is 46% (3 years after
first sexual encounter)1
1. Collins S, et al. Br J Obstet Gynaecol 2002; 109:96–98; 2. Schiffman M, et al. J Natl Cancer Inst 2003; 31:14–19;
3. Sellors JW, et al. CMAJ 2003; 168:421–425; 4. Dunne EF, et al. JAMA 2007; 297:813–819;
5. Brown DR, et al. J Infect Dis 2005; 191:182–192; 6. Koutsky L, et al. Am J Med 1997; 102:3–8;
7. Bosch FX, et al. J Natl Cancer Inst Monogr 2003; 31:3–13; 8. Castle PE, et al. J Infect Dis 2005; 19:1808–1816.
8. Castle PE, et al. J Infect Dis 2005;191:808–816;

14. The NEED for
vaccination against
Cervical cancer

15. 1.Stanley M. Vaccine 2006; 24: S106-13, 2.Tindle, Nat Rev Cancer 2002; 2, 59,
3.Stanley M. Vaccine 2006; 24: S16-22, 4. Stanley M. HPV Today 2007; 11: 1-16
No viremia
Local immunosuppression
No inflammation, no danger signals
Natural HPV infection induces a
weak immune response1-4

16. 1. Parr EL et al. J Virol 1997;71(11):8109-15, 2. Nardelli-Haefliger D et al. J Natl Cancer Inst 2003;95(15):1128-37, 3.
Schiller JT et al. Nat Rev Microbiol 2004;2(4):343-7, 4. Poncelet et al. ESPID, Porto, Portugal 2007; Abstract 37,
session ES2, 5. Stanley M. HPV Today 2007; 11: 1-16, 6. Einstein M, Cancer Immunol Immunother 2007; 57(4):443-
51.
Vaccination induces higher
antibodies in the blood and
site of infection
• Vaccine induces higher antibody levels
in the blood which means higher
antibody levels at the site of infection4
• These Antibodies neutralize the virus &
prevent entry into cells5,6

17. 1. Induce high antibody levels at the
basal epithelium of the cervix
2. Induce long lasting protection

18. Basic Characteristics of
CERVARIX and GARDASIL

19. Quadrivalent vs Bivalent Vaccine
Parameters Quadrivalent HPV Vaccine Bivalent HPV Vacine
Time of follow-up 36 months (advanced) 15 months (interim)
HPV types included 6, 11, 16, 18 16, 18
Efficacy HPV 16 or 18 CIN 2+ Proven Proven
Efficacy HPV 16 CIN 2+ Proven Proven
Efficacy HPV 18 CIN 2+ Proven Not yet provena
Efficacy 16 or 18 CIN 2 Proven Proven
Efficacy 16 or 18 CIN 3 Proven Not yet provena
Therapeutic efficacy None None
Efficacy on VIN 2/3 Proven Not yet reported
Efficacy on VAIN 2/3 Proven Not yet reported
Efficacy on genital warts Proven Not in target
Safety at 6 years follow-up Safeb
Safec
Tolerability Acceptable Acceptable
Cross protection (persistent HPV infection) 6 months 12 months
Cross protection (lesions) Reported Not yet reported
Duration of protectiond
5 – 6 years 5 – 6 years
Immunogenicityn preadolescents Proven Proven
Immunogenicity in older women Proven Proven
Immune memory at 6 years Proven Not yet reported

20. Worldwide
Guidelines

21. Organizations That Have Issued
Guidelines for Quadrivalent HPV Vaccine
• Advisory Committee on Immunization Practices (ACIP)
• American College of Obstetricians & Gynecologists (ACOG)
• American Cancer Society (ACS)
• American Academy of Pediatrics (AAP)
• American Academy of Family Physicians (AAFP)
• American College Health Association (ACHA).
• World Health Organization (WHO) - Consultation on HPV
vaccines
• Canada (National Advisory Committee on Immunization)
• Australia and New Zealand HPV Project
• High Council of Public Health - France
• The International Union Against Cancer (IUCC)
• Canadian Pediatric Society

22. ACIP & AAP - 2011
Consider giving HPV4 to
MALES age 9 through 26yrs to
reduce their likelihood of
acquiring genital warts.

23. IAP & FOGSI
• HPV vaccine should be given to
females from 9-45 years of age
for prevention of cervical
cancer.

24. GARDASIL®
indication as per DCGI
GARDASIL®
is indicated in females aged
9 through 45 years "for prevention of
cervical, vulvar, and vaginal cancer,
precancerous or dysplastic lesions,
genital warts, and infections caused
by Human Papillomavirus (HPV) Types
6, 11, 16 and 18 (which are included in
the vaccine).“

25. Clinical Trials
Overview

26. GARDASIL
Conclusions (FUTURE Trials)
• GARDASIL yields the greatest benefit in adolescent girls
prior to exposure to HPV
• However, women of all ages remain at risk for HPV-
related infection and disease
• Data demonstrate that women aged 24-45 benefit from
vaccination with GARDASIL
– GARDASIL showed a high level of efficacy against disease
caused by HPV Types 6/11/16/18 in this age group
– GARDASIL significantly reduced abnormal Pap tests caused by
vaccine HPV types
– Vaccination with GARDASIL may significantly impact the burden
of cervical cancer and HPV-related diseases among women
aged 24-45

27. A registry based long term
follow up (LTFU) study of
the Quadrivalent HPV
vaccine in
4
Nordic Countries

28. Future I (2002-06) - Age group – 16 to 24 years (end point cervical,
vulvar, vaginal, anal disease & warts) (n=5,455) Efficacy 100%
Future II (2004-08) - Age group – 15 to 26 years (n=12,167)
Extended as Nordic Study (end point cervical disease) Efficacy
100% Extended in Nordic region for 10 years
Future III (2004-08) - Age group – 24 to 45 years - Adult Woman
Efficacy Study (end point cervical, vulvar, vaginal diseases & warts)
(n=3,819) Efficacy 91%
Vaccine – Quadrivalent FUTURE Trials.
On the basis of causality established by monovalent vaccine, Phase 3 trials with Quadrivalent
vaccine started named as FUTURE Studies
FUTURE = Females United To Unilaterally Reduce Ecto/endo cervical diseases
Adolescent Study (’04-06) (N=4800) 9-15 yrs both sexes – 3 year extension
Male Efficacy Studies

29. 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

30. 2003 2004 2005 2006 2007 2008 20132010 2011 20122009
FUTURE II Study Registry-Based Follow-Up
VaccinationVaccination
Efficacy Reports
5 yr 7 yr 9 yr
4 yr 6 yr2 yr
2002
Launch in USLaunch in US
3.5 yr
Evaluation of Long-Term Disease
Protection: Follow-Up Through Registry
Program

31. Conclusions – Nordic Study
• Extensive monitoring of Gardasil is ongoing
in Nordic countries as an extension of
FUTURE 2 study.
• No breakthrough cases of HPV 16/18 related
CIN 2 or worse.
• GARDASIL shows a trend of continued
protection in women who were vaccinated up
to 7 years previously.
• GARDASIL continues to be generally safe
and well tolerated up to 6 years following
vaccination.

32. • Cervical cancer causes significant
morbidity/ mortality
• HPV vaccine to be offered to all
appropriate females who can afford the
vaccine
• Vaccine should be given prior to sexual
debut
www.fogsi.org/hpv vaccine

33. • Age for initiation of vaccination is 10- 12 years.
– Catch up vaccination is permitted up to the age of 45
years for both vaccine
• 3 doses at 0, 2 and 6 months with quadrivalent
vaccine
• 3 doses 0, 1 and 6 months with bivalent vaccine
www.fogsi.org/hpv vaccine

34. •At present there is no data to
support use of boosters

35. • Sexually active women and women
with previous abnormal cervical
cytology can receive the HPV vaccine
• Benefits may be limited to the
protection against infection of HPV
genotypes with which they have not
been infected

36. • The vaccine can be given to patients with
previous CIN, but the benefits may be limited to
the protection against infection of HPV
genotypes (and related CIN) with which they have
not been infected
• The HPV vaccine is not therapeutic. It does not
treat existing HPV infection or cervical
intraepithelial neoplasia (cervical pre-cancers)
FOGSI Recommendations:
Women With Previous CIN

37. –Not recommended for use in pregnancy
–If patient becomes pregnant - Delay remaining
doses till delivery
–If vaccinated during pregnancy - No
intervention (MTP) needed
–Lactating women can receive the HPV vaccine
(Gardasil) and still continue breastfeeding as it
is a vaccine without live viral DNA
FOGSI Recommendations:
Pregnancy & Lactation

38. • Vaccinated women should be screened as per
the standard guideline
• Screen positive women may be vaccinated
after counseling
• Screening/ HPV test is NOT REQUIRED prior
to vaccination
FOGSI Recommendations:
Vaccination & SCREENING

39. The WHO’s (World Health Organisation) Global
advisory committee on vaccine safety (GACVS),
the Vaccine adverse event reporting system
(VAERS), the Food & drug administration (FDA)
and the Centers for disease control &
prevention (CDC) have all confirmed and
declared that the HPV vaccination is safe &
effective providing protection against HPV 16,
18, 6 & 11 associated cervical, vulvar & vaginal
cancer, genital warts and other HPV-related
genital diseases in females.
Vaccination against HPV is safe & effective

40. • VACCINATION: One of greatest public health
achievements in the world
• With the exception of clean drinking water,
vaccines are the most effective intervention in
reducing and preventing the return of
infectious disease1
• 26 diseases are now vaccine preventable2
Let’s add Cervical Cancer to this list!
Value of Vaccination Today

41. Summary
 HPV is a necessary cause of cervical cancer – 99.7%
 Induction of neutralizing antibodies by vaccination is critical for
protection
 HPV 16 & 18 cause ~75%*
of cervical cancer cases while HPV 6
& 11 cause ~90% genital warts
 27% of the world burden of Cervical Cancer is seen in India.
 Every 7 minutes a woman dies in India due to cervical cancer
 Cervical Cancer is usually diagnosed in late stages in India.
 Cervical cancer screening is recommended in women >30yrs
 Vaccination between 9-45yrs can be an effective strategy to
help reduce this huge disease burden.

42. Let’s
Recap
HPV Vaccination

43. Is cervical cancer
common?

44. What is the best age to vaccinate?

45. Is there any benefit in vaccinating
sexually active women?

46. Why do we need to vaccinate
women in monogamous
relationships?

47. Do we need to screen before
vaccination?

48. Do we need to screen after
vaccination?

49. Looking at the high cost of
vaccination is it not better to
screen?

50. What is expected of a good
cervical cancer vaccine?

51. What are the key differences
between the two vaccines?

52. Head- to-Head comparison
between the two vaccines?

53. Efficacy & Duration of Protection?

54. Which are the global bodies that
have recommended vaccination?

55. What about safety and adverse
effects?

56. How should it be administered?

57. Thank You