Transcript PAP Smear

CERVICAL CANCER
& ITS PREVENTION
-Dr.MEETA AGRAWAL,
Obs & Gynae., Bhopal
Educational Program 2009
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Sad but True…
In India, 200 women die
each day due to Cervical
cancer
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For you & your daughter …..a
wonderful gift
Guard Yourself means
Protect yourself
very special programme
to prevent cervical cancer.
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where is cervix in woman?
CERVIX
Educational Program 2015
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What is cancer?
• Uncontrolled growth of abnormal cells in
any part of the body.
• Generally due to
1. chemicals (e.g. From smoking )
2. radiation
3. micro-organisms (e.g. Bacteria, viruses)
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Cervical Cancer – Disease Burden
New Cervical Cancer Cases
Deaths due to Cervical cancer
India ~1,32,000
World ~ 4,93,000
India ~ 74,000
World ~ 2,73,000
India ~27%
India ~27%
- 27%
India
Rest of World - 73%
Rest of World - 73%
India ~27% of new
Cervical Cancer cases in world
Rest of World - 73%
India ~27% of deaths
due to Cervical Cancer in world
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Incidence ( Women of all ages) – Cervical
Cancer vs. other Cancers
2. 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
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Cervical Cancer in the World. 2007 Report. WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre). Available at: www.who.int/hpvcentre
Human Papillomavirus (HPV)
HPV is a necessary cause of cervical cancer – 99.7%4
Cancer causing Types1,2,4
HPV
Non-cancer causing types1,2
HPV 16
HPV 6
HPV 18
HPV 11
• >75% of Cervical Cancer5
• >50% of Vaginal & Vulvar Cancer5
90% of Anogenital warts5
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/hpvcentre
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


Anogenital Disease: cervix, vulva, vagina, anus, penis
 Condylomata accuminatum
 Squamous intraepithelial neoplasia
 Cancer
Head/Neck Disease:
 Mouth, tongue, tonsils
 Sinuses
 Oropharangeal
 Respiratory mucosa (children; type 6, 11)
 Cancer: usually HPV 16
Cofactors: Smoking, Alcohol
5 – 10 years to develop cancer from time of infection
Infects only the epithelium – no viremia
Most cases – no histologic or cytologic changes (66% - 90%)
• Resolution of infection and cytologic changes occurs secondary to
antibodies, and NKC, activated CD-4 and T lymphocytes
HPV
Infection
Measured by HPV DNA
detection in cervical cells
Relative frequency
increases with severity of
lesion
Cervical
Lesions
Invasive
Cancer
Ranges
from
Normal
Development of Precancerous lesions
CIN1, CIN2 & CIN3
Long term use of Hormonal Contraceptive
-> 5-9yrs :: 3 times Risk
-> 10yrs or more :: 4 times Risk
Other STI’s
->Chlamydia Trachomatis
-> HSV 2
Early initiation of Sexual Activity
Immune Suppression
High Parity :: 4 times Risk
HIV Infection
Tobacco Smoking (Both active & passive)
Multiple Sex Partners
Low S/E status ; Diet poor in anti oxidants

Normal
Cervix
Infection
Clearance
Persistence
Progression
HPV
Infection
Invasion
Pre-cancer
Regression
Cancer
CIN (CERVICAL INTRAEPITHELIAL NEOPLASIA)
as Seen in Colposcopy
Colposcopy findings confirmed by histology1
CIN 1
Photo courtesy of Dr. J. Monsonego
CIN 2
Photo courtesy of Dr. J. Monsonego
CIN 3
From IARC, 2003.4
1. Wright TC Jr, Cox JT, Massad LS, et al, for the ASCCP-Sponsored Consensus Congress. JAMA. 2002;287:2120–2129. 2. Bonnez W. In: Richman DD,
Whitley RJ, Hayden FJ, eds. Washington, DC: American Society for Microbiology Press; 2002:557–596. 3. Canadian Cancer Society. Cervical Cancer: What
you need to know. Available at: http://www.cancer.ca/vgn/images/portal/cit_86751114/63/40/151140772cw_library_wyntk_cervical_en.pdf. Accessed March 13,
2006. 4. Reprinted with permission from Sellors JW, Sankaranarayanan R, eds. Colposcopy and Treatment of Cervical Intraepithelial Neoplasia. A Beginner’s
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Manual. Lyon, France: International Agency for Research on Cancer; 2003.
How HPV infection can occur?
 Through sexual intercourse, vertical
transmission i.e. mother to child &
fomites.
 It is found that in every 10 women 8
women might have HPV infection at
anytime in life.**Ref: CDC Factsheet on Genital HPV infection
www.cdc.gov/STD/healthcomm/factsheet.html
Educational Program 2009
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Beware of this symptoms
Consult your doctor immediately if you have
•
•
•
•
•
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Continuous vaginal discharge,inspite of treatment
Foul smelling, thick discharge,
Repeated vaginitis and UTI
Post coital bleeding(bleeding after sex)
Non healing or recurrent cervical erosion
Irregular or intermenstrual bleeding specially in pre
menopausal phase
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Cervical cancer screening
•
•
•
•
Chronic pain
distension
loss of weight
Heavy prolong bleeding ,before or during
menopausal age
• Post menopausal bleeding-important
• Cervical polyp
• tumor during or before menopause age
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Is it possible
to get
protection
against
cervical cancer?
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Cervical Cancer is now a virtually preventable disease due to
 Early Vaccination
 Screening strategies
 Long natural history
 Cervix is easily accessible
Secondary Prevention
Screening may help in early detection
of cervical abnormalities
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What is the use of screening
program?
• Secondary prevention or screening
program are helpful in detecting cancer
at the early stage hence useful in saving
lives.
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Visual Inspection
VIA
VILI
Pap Smear
Conventional
LBC
HPV DNA Testing
Cervicography
Pap Net
Polar Probe
Community low
resource
settings
Still Experimental
Population
USPSTF
ACS/ASCCP/ASCP
Younger
than 21
years
Recommends against screening.
Women should not be screened regardless of the age
of sexual initiation or other risk factors. ?
Grade: D recommendation.
21–29 years Recommends screening with cytology
every 3 years.
Screening with cytology alone every 3 years is
recommended.
Grade: A recommendation.
30–65 years Recommends screening with cytology
Screening with cytology and HPV testing (“coevery 3 years or for women who want testing”) every 5 years (preferred) or cytology alone
to lengthen the screening interval,
every 3 years (acceptable) is recommended.
screening with a combination of
cytology and HPV testing every 5
years.
Grade: A recommendation.
Population
USPSTF
ACS/ASCCP/ASCP
Older than 65
Recommends against screening
Women with evidence of adequate negative prior
years
women who have had adequate prior screening and no history of CIN2+ within the last 20
screening and are not otherwise at years should not be screened. Screening should not
high risk for cervical cancer.
be resumed for any reason, even if a woman reports
having a new sexual partner.
Grade: D recommendation.
After
Recommends against screening in
Women of any age following a hysterectomy with
hysterectomy
women who have had a
removal of the cervix who have no history of
hysterectomy with removal of the
CIN2+ should not be screened for vaginal cancer.
cervix and who do not have a
Evidence of adequate negative prior screening is not
history of a high-grade precancerous required. Screening should not be resumed for any
lesion (i.e. CIN 2 or 3) or cervical
reason, including if a woman reports having a new
cancer.
sexual partner.
HPV
vaccinated
Grade: D recommendation
Women who have been vaccinated Recommended screening practices should not change
should continue to be screened
on the basis of HPV vaccination status.
PAP Smear
 PAP smear sampling of cervix involves scraping of
cervical surface and a portion of non visualised
cervical canal using various sampling devices
 disasters “prevention is better than cure’holds true for cervical cancer
 This can be achieved by regular health
check up and regular pap smear test
 Pap- smear is cancer screening which is easy
,painless and reliable method in which the
discharge from vagina is taken on slide and
sent for examination for presence of
abnormal cells
 Routine pap smear has reduced ca cx by 75%
in developed world
 Repeat pap is advised if it shows abnormal
cells & than advised colposcopy & biopsy.
 It can give early diagnosis of cancer before
its sets in and hence early treatment can
avoid disease
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Significance of Pap smear
 Detect precancerous & invasive cancer cervix cases in
early stages
 Positive screeners can be selected for selective tests and
management
 With treatment, progression of disease is halted. Thus
morbidity associated with advanced cancer decreases
 Mortality reduces by 20-60 %.
 Helps us to study natural history of disease.
Transformation zone
 Cervix develops from 2 embryonic sites
* from Mullerian duct - lined by columnar epithelium
* from urogenital plate - lined by stratified
squamous epithelium
 Point at which columnar and squamous epithelium
meet is called as original squamo-columnar
junction
Transformation zone
 Under influence of estrogen, original SCJ moves
onto the portio.
 Exposure of delicate columnar cells to vaginal
environment leads to squamous metaplasia.
 Transformation zone - Area of squamous metaplasia
- Area between original and new SCJ
Transformation zone
Transformation Zone -TZ
 Exposure of TZ to carcinogens begins the process of
intraepithelial neoplasia
 While exact role of carcinogens in this process remains poorly
understood, it is clear that HPV and cigarette smoking can
cause dysplasia at the TZ
 95% of cervical cancers develop in TZ
 Important to take sample from TZ
PAP SMEAR
• The cells are taken from the cervix region by
speculum & spatula, then smear is prepared
which is then observed under microscope.
• It is not recommended in virgin females.
• Recommended in every 3 years to all female
aged more than 30 years.
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How to take a Pap Smear ?
 Spatula is rotated through 360 degrees
maintaining contact with ectocervix
 Do not use too much force [bleeding /pain]
 Do not use too less force [inadequate sample]
 Sample is smeared evenly on the slide and fixed
immediately
 Both sides of spatula are to be smeared
How to take a Pap Smear ?
 Endocervical sample is collected using an
endocervical brush
 Insert the cytobrush into canal, so that last bristles
of brush are visible
 Rotate the brush through 180 degrees. [more
rotations increase the chance of bleeding]
 Sample is rolled on the slide and fixed.
Fixation of smear
 Fixation is done immediately with
fixative like 95% alcohol or cytofix
spray to avoid air drying
 Spray should be kept at 10 inches, to
avoid destruction of cells by
propellent in the spray
 Smear should monolayer for proper
penetration of cell surface by fixative
Fixation of smear
 Fixation is done immediately with
fixative like 95% alcohol or cytofix
spray to avoid air drying
 Spray should be kept at 10 inches, to
avoid destruction of cells by
propellent in the spray
 Smear should monolayer for proper
penetration of cell surface by fixative
Liquid Based Cytology
 Several slides can be prepared from one smear
 Chlamydia, HPV testing can be done at later date
 Reduces the incidence of inadequate and repeat smears

The HPV test is a very accurate way to tell if high-risk HPV is present in a
woman’s cervix.

This test can use the same sample of cells taken for the Pap test.

A positive test result means a woman has high-risk HPV.
A positive HPV test does not mean that a woman has cancer.

To see if a woman with a borderline Pap test result
(one that shows unusual cells but not dysplasia)
needs additional tests.

To screen for cervical cancer, along with the Pap
test, in women aged 30 or older.
• Only less than 1% progress to cancer
• Lifetime risk of genital HPV: 50-80%
• Lifetime risk of genital warts: 5%
• Risk of ICC in Women
• 4% :: No screening with Pap
• 1% :: With regular screening
• Pap test is used to find cellular abnormalities in Cervical tissue for
Early Diagnosis
COLPOSCOPY
Colposcopy is the examination of the cervix &
vagina with a light magnifying instrument
colposcope after the application of a vinegar
(acetic acid) to the cervix.
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Colposcopy
• Magnified visual examination of uterine cervix by a low
power ,stereoscopic microscope with a powerful light
source to help in diagnosis of cervical neoplasia .
• Key ingradients –observations of features of cervical
epithelium after application of normal saline , 3-5% dilute
acetic acid and Lugol’s iodine solution .
•
INDICATIONS OF COLPOSCOPY
•
•
•
•
•
•
•
•
•
•
Squamous or glandular cell abnormalities
Persistence of inflammatory cells despite adequate tt
Presence of keratinized cells .
VIA +ve and VILLI+ve
Evaluation of HPV +ve women .
Postcoital ,postmenopausal bleeding .
Unhealthy cervix .
Treatment and monitoring of women with CIN
Anogenital condylomas ,VIN and VAIN.
DES exposure in utero.
Colposcopy - Objectives
 Determines the presence of invasive cancer
 Localizes the squamocolumnar junction
 Identifies the most severe disease for biopsy
 Evaluates the extent of disease
A method of identifying
outer & inner borders of the transformation zone
The entire new SCJ is visible
colposcopic examination is satisfactory.
the TZ is fully visualized. The metaplastic
squamous epithelium is pinkish-white
compared to the pink original squamous
epithelium
Post Menopausal Cervix:
Epithelium is pale, brittle, lacks lusture,
shows sub-epithelial petichiae, SCJ not
visualized
Squamous metaplasia
Earliest colposcopic changes in
immature squamous metaplasia
(after 5% AA) in which tips of
columnar villi stain white & adjacent
villi start fusing together
Prominent white line corresponds to
the new SCJ & tongues of immature
Squamous metaplasia a) with crypt
openings at 4-8 o’clock positions
b) after application of AA
Immature squamous metaplastic epithelium (narrow arrow)
on the polyp with intervening areas of columnar epithelium
a) after application of AA
The endocervical polyp &
the immature squamous metaplasia
surrounding the os partially take up
iodine.
Immature squamous metaplastic epithelium (narrow arrow)
on the polyp with intervening areas of columnar epithelium
a) after application of AA
The endocervical polyp &
the immature squamous metaplasia
surrounding the os partially take up
iodine.
Leukoplakia
 Usually benign
 May obscure an underlying
neoplasia
 Therefore, all patches
observed before application of
acetic acid must be biopsied
Hyperkeratosis ( Leukoplakia)
CIN (CERVICAL INTRAEPITHELIAL NEOPLASIA)
as Seen in Colposcopy
Colposcopy findings confirmed by histology1
CIN 1
Photo courtesy of Dr. J. Monsonego
CIN 2
Photo courtesy of Dr. J. Monsonego
CIN 3
From IARC, 2003.4
1. Wright TC Jr, Cox JT, Massad LS, et al, for the ASCCP-Sponsored Consensus Congress. JAMA. 2002;287:2120–2129. 2. Bonnez W. In: Richman DD,
Whitley RJ, Hayden FJ, eds. Washington, DC: American Society for Microbiology Press; 2002:557–596. 3. Canadian Cancer Society. Cervical Cancer: What
you need to know. Available at: http://www.cancer.ca/vgn/images/portal/cit_86751114/63/40/151140772cw_library_wyntk_cervical_en.pdf. Accessed March 13,
2006. 4. Reprinted with permission from Sellors JW, Sankaranarayanan R, eds. Colposcopy and Treatment of Cervical Intraepithelial Neoplasia. A Beginner’s
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Manual. Lyon, France: International Agency for Research on Cancer; 2003.
Geographic satellite lesion
condyloma
low-grade lesion
Thin acetowhite lesion with
geographic margins in the upper
lip. Histology indicated CIN 1
Moderately dense acetowhite
lesions with irregular margins in the
anterior & posterior lips ( CIN 1)
circumorificial acetowhite CIN 1
lesion with irregular margin & fine mosaics
Moderately dense acetowhite lesions with well
defined margins & coarse punctations in the
anterior lip & in 3 o’clock position (CIN 2 lesion
Dense well defined acetowhite
area with regular margins &
coarse mosaic ( CIN 2 lesion )
A dense acetowhite lesion with varying colour
intensity &
coarse mosaics (a) in a CIN 2 lesion
Acetowhite lesions with coarse punctation
(a) & mosaics (b) in a CIN 2 lesion
A circumoral dense opaque acetowhite area with
coarse mosaics ( CIN 3 lesion)
A dense acetowhite lesion with regular
margin & coarse,
irregular punctation in a CIN 3 lesion.
Carcinoma in Situ
Preclinical invasive
Carcinoma
Early invasive cancer: note the raised irregular mosaics with umbilication (a), breaking
mosaics (b), surface irregularity & the atypical vessels after the application of 5% AA
Inflammatory lesions of the
Uterine Cervix
Reddish “angry-looking”, inflamed columnar
epithelium with loss of the
villous structure & with inflammatory exudate
(before application of 5% AA)
Chronic cervicitis: This cervix is
extensively inflammed with a reddish
appearance &
bleeding on touch, there are illdefined, patchy acetowhite areas
scattered all over the cervix after the
application of AA
TV after Acetic acid
Multiple red spots (a) suggestive of Trichomonas
vaginalis colpitis ( strawberry appearance), after
application of 5% AA
T.V. After Lugol’s
Trichomonas vaginalis colpitis
after application of Lugol’s iodine
(leopard-skin appearance)
Primary Prevention
by HPV Vaccine
GARDASIL
®
[Human Papillomavirus Quadrivalent
(Types 6, 11, 16, and 18)
Vaccine 0.5ml prefilled syringe]
CERVERIX
[Human Papillomavirus Bivalent
(Types 16 and 18)
Vaccine 0.5ml prefilled syringe]
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09-2009-GRD-2008-AP-(IN)-1601-SS
HPV Vaccines- made by
recombinant DNA technology
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INDICATION
FOR Gardasil
For the prevention of
Cervical Cancer
Vulvar/ Vaginal Precancers
Cervical Dysplasia
Genital Warts
Cerverix is only indicated for
Cervical cancer
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Effectiveness
 Gardasil vaccine’s efficacy is 98 to
100%.
 Cerverix vaccine’s efficacy is 92 to
94%
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When we can give this vaccine?
 This vaccine can be given to any
girl above 9 years. Recommended
for women of 9-45 years age group
 The most effective time to
vaccinate girls and young women
is before they become sexually
active.
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How many dose recommended?
 Three doses
 First .(as elected date)
 Second (after 2 month of first dose)
 Third (after 6 month of first dose)
Cerverix – 0,1 & 6
0
2
Months
6
months
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Side effects
• HPV Vaccines demonstrated a favorable safety profile.
• Following injection-site reactions occurred at a greater
incidence in the group that received VACCINE
– Very common: erythema, pain, and swelling.
– Common: pruritis.
– Most injection-site reactions were mild to moderate.
– Very Common (≥1/10); Common (≥1/100, <1/10); Uncommon (≥1/1,000, <1/100); Rare
(≥1/10,000, <1/1,000); Very Rare (<1/10,000)
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Special Population
PREGNANT WOMEN
 Because of insufficient trial there is no
recommendation of this vaccine in
pregnancy.
 If woman gets pregnant after first dose ,then
remaining dose should be taken after
delivery.
LACTATING MOTHER
 Lactating woman can take this vaccine.
Cerverix is not indicated during lactation
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Is vaccine costly?
 No, if we can see the mortality
rate of the cervical cancer or its
treatment ,vaccine cost is
nothing against it.
 If we see the modern life style of
people ,vaccine cost is nothing.
 People give lacks of rupees of
dowry to their daughters ,vaccine
cost is nothing against it.
 It is cost effective
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Educational Program 2009
Screening & Vaccination
 Pap testing and screening for HPV DNA or HPV
antibody are not needed before vaccination at any age.
• Benefits may be limited to protection against HPV
genotypes with which they have not been infected.
• Women infected with vaccine HPV-type and have
cleared the cervical infection appears to have
similar protective effects as in HPV naïve to the
same vaccine HPV-type.
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Gardasil Approvals: 156 countries
Europe:
Caribbean & Central America:
North America:
Costa Rica
Puerto Rico
Guatemala
Curaçao
Bermuda
Bahamas
Barbados
Jamaica
Trinidad
El Salvador
Honduras
Nicaragua
Panama
Cayman Islands
Aruba
Dominican Republic
USA
Canada
Mexico
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South America:
Brazil
Argentina
Peru
Colombia
3
Bolivia
Uruguay
Ecuador
Chile
16
8
Middle East & Africa:
Gabon
Israel
Morocco
Kenya
Mauritania
Guinea Eq.
Uganda
Malawi
Jordan
Cote d’Ivoire
Chad
Saudi Arabia
South Africa
Congo Kinshasa
C.A.R.
Mauritius
Kuwait
UAE
Ethiopia
Togo
Congo Brazzaville
Egypt
Burkina Faso
Bahrain
Botswana
Cameroon
Germany
France
UK
Spain
Italy
Austria
Belgium
Bulgaria
Portugal
Slovenia
Montenegro
Turkey
Russia
Georgia
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Cyprus
Czech Republic
Denmark
Estonia
Finland
Greece
Hungary
Iceland
Romania
Sweden
Switzerland
Croatia
Macedonia
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Ireland
Latvia
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Slovakia
Serbia
Liechtenstein
Bosnia
Belarus
Asia Pacific:
Australia
Indonesia
Korea
Taiwan
Hong Kong
Singapore
New Zealand
Macau
Malaysia
Philippines
Thailand
India
Vietnam
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Is this vaccine is using with another
developing country?
 Yes, this vaccine is available in 156 country.
till date 200 million doses already used
within 9 years of time.
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But
PRIMARY PREVENTION
is most important.
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Preventing aspects-lifestyle change
Social change –avoid early marriages
Multiparity_ role of family planning
Avoid multiple partners
Use of condom to avoid STD,and HPV diseases
Improve nutrition and personal hygiene
Prevents smoking ,alcoholism ,etc
Regular exercise
Health awareness-health check up
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To produce a Cancer Free Society
Screening and identification of High Risk groups
Education – Think of Cervical Cancer as an
extension of STD
Behavioral changes
Limit number of sexual partners
Delay initial age of sexual intercourse
Avoid STD – Use of Condoms/ Spermicidals;
Avoid Smoking
HPV Vaccines to be promoted at the right age
Lets fight against cancer
…..join hands……
…..take preventive measures…….
…..update yourself…..
…..take care…..
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