Slayt 1

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Prospects for a Prophylactic HPV Vaccine and
Future Implications for Cervical Cancer
Screening
Dr. Fuat Demirkiran I.Ü Cerrahpasa Tip Fak. Kadin
Hast. ve Dogum ABD, Jinekolojik Onkoloji Bilim
Dali Antalya ,2011
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Prevalence of cervical cancer in the world
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case increase 50-55
case increase 6-23
World population prospects for women gt15 years.
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Secondary prevention
Primary prevention
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Faz III Etkinlik Sonuçlari
Cervarix (15 aylik takip Paavonen Lancet 2007) N18,644 Gardasil (3 yillik takip Koutsky et al. NEJM 2007 N12,167 Garland et al. NEJM 2007 N5,455)
CIN 2/3 HPV 16/18e bagli 90 (97.9 GA 53-99) P/V 21/2 olay, TVC 100 (97.9 GA 74-100) P/V 20/0 olay, PPR 95 (95 GA 85-99) P/V 62/3 olay, USP 98 (95 GA 86-100) P/V 42/1 olay, PPSP
CIN 1 HPV 16ya bagli HPV 18e bagli 94 (97.9 GA 54-100) P/V 17/1 olay, PPR 100 (97.9 GA 34-100) P/V 9/0 olay, PPR 100 ((95 GA 93-100) P/V 53/0 olay, USP 95 ((95 GA 72-100) P/V 22/1 olay, USP

• Ilk doz sonrasi
• Kadinlar 0. günde asiya özgü HPV tipleri için
  negatif

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American Cancer Society (ACS) Recommendations for
Human Papillomavirus (HPV) Vaccine Use to Prevent
Cervical Cancer and Its Precursors 2007
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CDC
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March 2009
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The Countries that are made reimbursement
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Screening for cervical pathology should be go
on after vaccination
Efficacy of HPV vaccines
Barriers to HPV vaccine and covarage rate
New HPV infection in advanced ages
Based on statistical analysis of HPV type
distributions in populations, it appears
unlikely that reducing the frequency of specific
HPV types in a population through vaccination
would lead to an increase in the frequency of
other HPV types
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Worldwide distribution of HPV types in cervical
cancer
Cancer cases associated with most frequent HPV
genotypes ()
1. Munoz N. Against which human papillomavirus
types shall we vaccinate and screen? The
international perspective Int J Cancer 2004 111
27885.
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Efficacy Against HPV 6/11/16/18 Related CIN 2/3
or Worse and AIS (Protocols 005, 007, 013, and
015)
Gardasil Gardasil Gardasil Placebo Placebo Placebo
Day 1 Status N No. cases Incidence N No. of cases Incidence Efficacy 95 CI
MITT-3 9831 122 0.7 9896 201 0.9 39.0 (23.3, 51.7)
PCR (-) Sero (-) 9342 1 0.6 9400 81 0.4 98.8 (92.9, 100.0)
PCR (-) Sero () 853 0 0.0 910 4 0.2 100 (-63.6, 100.0)
PCR () Sero (-) 661 42 3.2 626 57 4.6 31.2 (-4.5, 54.9)
PCR () Sero () 473 79 121 9.1 499 69 130 7.3 -25.8 (-76.4, 10.1)
Total number of cases in subjects who were
sero and/or PCR at baseline for the relevant
HPV type which was associated with
disease. Source Table 1-1, Additional efficacy
analysis requested by CBER
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Gynecologic Oncology 115 (2009) S15S23
In fact, in the total vaccinated cohort, efficacy
against any CIN II/III irrespective of HPV type
was 30.4 at 39 months after the first
vaccination and is expected to increase with
longer follow-up.
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Worldwide female population and a speculative
anticipation on the initial introduction of HPV
vaccines.
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Covarage Rate
Expanded Program of Immunization 19802005 DTP3
coverage by level of development
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HPV Vaccination Coverage by dose number, age in years as at mid 2007 and place of vaccination, as notified for the National HPV Vaccination Program catch up cohorts (Avustralia Women vaccinated between April 2007-December 2009) HPV Vaccination Coverage by dose number, age in years as at mid 2007 and place of vaccination, as notified for the National HPV Vaccination Program catch up cohorts (Avustralia Women vaccinated between April 2007-December 2009) HPV Vaccination Coverage by dose number, age in years as at mid 2007 and place of vaccination, as notified for the National HPV Vaccination Program catch up cohorts (Avustralia Women vaccinated between April 2007-December 2009) HPV Vaccination Coverage by dose number, age in years as at mid 2007 and place of vaccination, as notified for the National HPV Vaccination Program catch up cohorts (Avustralia Women vaccinated between April 2007-December 2009) HPV Vaccination Coverage by dose number, age in years as at mid 2007 and place of vaccination, as notified for the National HPV Vaccination Program catch up cohorts (Avustralia Women vaccinated between April 2007-December 2009) HPV Vaccination Coverage by dose number, age in years as at mid 2007 and place of vaccination, as notified for the National HPV Vaccination Program catch up cohorts (Avustralia Women vaccinated between April 2007-December 2009) HPV Vaccination Coverage by dose number, age in years as at mid 2007 and place of vaccination, as notified for the National HPV Vaccination Program catch up cohorts (Avustralia Women vaccinated between April 2007-December 2009)
Place of Vaccination Place of Vaccination School Program School Catch Up School Catch Up GP/community GP/community
Age (in years as at mid 2007) Age (in years as at mid 2007) 12-13 14-15 16-17 18-19 20-26
Population (as at mid 2007) Population (as at mid 2007) 275,597 277,689 282,408 281,065 1,031,500
Total No of Doses Notified Total No of Doses Notified 649,310 652,014 624,410 433,856 1,278,678
Coverage rate as at 21 Mar 2011 Dose 1 83 84 81 64 52
Dose 2 80 79 75 53 42
Dose 3 73 72 66 38 30



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Prevalence of HPV infection, precancerous lesions
and cervical cancer by age of women
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at least 5
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Age-specific incidence of oncogenic HPV
infections in Ontario, Canada , Adapted from
Sellors et al.
in different regions of the world have shown that
each year between approximately 5 and 15 of
sexually active mid-adult women acquire a new
infection with an oncogenic HPV type
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Gynecologic Oncology 115 (2009) S15S23
Approximately 515 of sexually active
midadult women acquire a new infection with an
oncogenic HPV type each year and in approximately
12 of these women, the responsible oncogenic
HPV types will be HPV-16 or -18
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CIN3
HPV16
HPV18
HC2
Cumulative incidence of cervical intraepithelial
neoplasia grade 3 and cancer ( CIN3) over a
10-year period in 12 976 women 30 years old
and older with negative cytology at enrollment,
according to oncogenic human papillomavirus (HPV)
status at enrollment. HPV status is defi ned
hierarchically as positive for HPV 16 ( closed
circles ), else positive for HPV18 ( open circles
), else positive for the non-HPV16/18 oncogenic
types in Hybrid Capture 2 (HC2) ( closed
triangles ), else oncogenic HPV negative ( open
triangles ).
HC2-
Cumulative incidence of cervical intraepithelial
neoplasia grade 3 and cancer ( CIN3) over a
10-year period in 20 514 women according to
oncogenic human papillomavirus (HPV) status at
enrollment. HPV status is defi ned hierarchically
as positive for HPV 16 ( closed circles ), else
positive for HPV18 ( open circles ), else
positive for the non-HPV16/18 oncogenic types in
Hybrid Capture 2 ( closed triangles ), else
oncogenic HPV negative ( open triangles
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It is unclear whether new acquisition or
reactivation of a latent infection is responsible
for the higher detection rates observed in older
women. It has been proposed that what we call
incident infections at higher ages may be due to
new infections as well as reactivation of latent
persistent infections
it is unclear whether a prophylactic vaccine
can be efficacious in preventing reactivation of
latent infection.
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Any suggested screening program.
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Implementation of a prophylactic HPV vaccination
program would have important implications for
cervical cancer screening. During the initial
period following the introduction of a vaccine
program, the population will include
both vaccinated women at low risk for cervical
neoplasia and women who have not been vaccinated
who will be at greater risk.
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TEN MOST FREQUENT HPV TYPES AMONG HIGH GRADE
CERVICAL LESIONS WORLDWIDE
WORLD
DEVELOPING REGIONS
DEVELOPED REGIONS
Data source IARC Infection and Cancer
Epidemiology Group. Clifford et al Br J Cancer
2003, Smith et al Int J Cancer 2007
Available at HPV Information Centre. Human
Papillomavirus and Related Cancers in World.
Summary Report 2009. Accessed 27 May 2010.
Available at www. who. int/ hpvcentre
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TEN MOST FREQUENT HPV TYPES AMONG LOW GRADE
CERVICAL LESIONS WORLDWIDE
WORLD
DEVELOPING REGIONS
DEVELOPED REGIONS
Data source IARC Infection and Cancer
Epidemiology Group. Clifford et al CEBP 2005
Available at HPV Information Centre. Human
Papillomavirus and Related Cancers in World.
Summary Report 2009. Accessed 27 May 2010.
Available at www. who. int/ hpvcentre
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Vaccination of adolescents reduction in rates
of HPV infection
low-grade SIL High-grade
SIL- Cancer
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With Vaccination program, over time The SILs
remaining in the population would be related
increasingly to HPV types that are less likely to
persist and to progress to cancer.
Consequently, there would be fewer SILs in the
population, and the SILs remaining would be more
likely to spontaneously regress without treatment.
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In general population, the
lifetime risk for developing carcinoma in
women with low-grade SIL..1. In
vaccinated population, this
risk.1/500-1000
Would LSIL require treatment ?

focus on the detection of high-grade SIL.
After post-vaccination program
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Increase incidence of low risk lesions following
vaccination
Many problems related to screening program
after Broad-Spectrum Vaccination
Decrease the alertness of the cytology screeners,
decrease the positive predictive value of
cytological screening.
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Long term impact of vaccination
As time goes on, more women will receive the HPV
vaccine before the onset of sexual activity. This
will result in a fall in positive predictive
value of the Pap test.
Modifications to the screening Program. a
change in the age of commencement of screening,
a change to the screening interval, the
addition of HPV DNA tests.
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Cost-efective cancer prevention in
HPV-vaccinated population.
probably require targeted screening with HPV
testing
a few times during entire lifetime
secondary screening with cytology
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.
Combining vaccination with screening still will
be the most effective way to reduce the lifetime
risk of cervical cancer in next years.
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Forward looking views on cervical cancer
prevention strategies
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Widespread implementation of an HPV vaccine
program is unlikely to occur until the next
century, and its impact would not be fully
appreciated for decades.
Dramatic changes in screening program of cervical
cancer has not been seen reasonable for next
few decades.
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Modifications to the screening program will be
necessary in the long term.
A clear message is that the vaccine is not a
substitute for screening tests
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