Angelica Agapito, MD
2
Every 2 minutes, a woman dies of cervical cancer.
FSM
Incidence: 493,000 new cases per year; 245,000 in Asia (50%)
< 13.6* < 23.5* < 37.9* < 47.3* < 126.6*
50% deaths/year (83% from Asia)
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Ferlay J et al . Globocan 2002. IARC 2004; Parkin DM et al. eds. Cancer Incidence in Five Continents ,
Vol. VIII. IARC, 2002; http://www.who.int/healthinfo/statistics/bodprojections2030/en/index.html
;
Greimal E et al. Gynecol Oncol 2002;85:140 –7
3
*Rate per 100,000 population (all ages)
LEADING CANCER SITES IN
WOMEN
ORAL (1)
UTERUS (5)
OVARY (4)
BREAST(3)
CERVIX (2)
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Incidence high
34/100,000
72% die in 5 years
2/3: late stage
Actual situation may even be underestimated
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The 4 Most Common Cancercausing Virus Types
HPV virus types
16 and 18 account for 71% of all cervical cancer cases worldwide 1
HPV types 45 and
31 account for an additional 9%
1. Munoz N, Bosch FX. Et al IJC 2004
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Months
Natural History: From Infection to Cervical Cancer
Years
Normal epithelium
80%
HPV infection CIN I CIN
2 CIN
Pre-cancerous lesions
From incident to persistent HPV infection
3
Invasive cervical cancer
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Monsonego J (ed): From Science to Practice. 2006, pp I-XII
8
Sexual activity before age 20
Multiple sexual partners
Exposure to STI
Mother and sister with cervical cancer
Previous abnormal Pap smear
Smoking
Immunosuppression
HIV/AIDS
Chronic corticosteroid use
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Who Gets Cervical Cancer?
Every woman is at risk.
Usually in their mid to late reproductive years
80% of women who get cervical cancer live in developing countries
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Prevention:
Have a Healthy Lifestyle
Regular exercise
No smoking
Eat a balanced diet
Get enough rest
Avoid stress
Have a mutually monogamous relationship
Regular medical checkup
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Against HPV
Reduce infection that may cause cancer
Protective against only some types of HPV
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Who Would Benefit from Screening for
Precancerous Changes?
ALL Women would benefit from screening for precancerous changes.
Only about 5% of women in developing countries have been screened for cervical cancer in the past 5 years
Women who are not screened and treated for precancerous changes get cervical cancer
Approximately 70% of women in the US and
European countries have been screened for cervical cancer in the past 5 years
Screening and treatment has helped reduce invasive cervical cancer incidence by as much as 90%
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When Should a Woman Be
Screened for Cervical Cancer?
Every woman should be screened for cervical cancer at least once sometime during her life
Women should be screened up to age 45 with VIA
Screening should begin at least a decade before the peak incidence of cervical cancer in a country
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Complex laboratory test
Requires trained cytotechnician for reading and pathologist for review
Reports often take 1-6 weeks to obtain
Follow-up of women is difficult
Usually available only in large cities in many countries
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VIA/VIAM 1
Automated Pap Smear
HPV/DNA Test
Cervicography
Yes Yes Yes Yes Yes
Yes Yes No No No
Yes Yes No
Yes Yes No
No
No
No
No
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1 Visual inspection of the cervix using acetic acid (VIA) and with magnification (VIAM).
Source: PATH 1997.
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COMPARING VIA AND PAP SMEAR
Zimbabwe CCS Study
Phase 2 Results
TEST SENSITIVITY
(%) *
SPECIFICITY
(%) *
VIA
(n=2,130)
77
(70-82)
64
(62-66)
POSITIVE
PREDICTIVE
VALUE (%) *
19
NEGATIVE
PREDICTIVE
VALUE (%) *
96
Pap
Smear
(n=2.092)
44
(35-51)
91
(37-51)
*95% Confidence Interval
Source: University of Zimbabwe/JHPIEGO Cervical Cancer Project 1999
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33
17
94
18
• Abwao, et al 1998
• Sankaranarayanan et al 1999
• University of Zimbabwe/JHPIEGO
Cervical
Cancer Project, 1999
• Denny et al, 2000
• Ngelangel et al , 200
1
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VIA
Visual Inspection with Acetic
Acid
best alternative to
Pap smear (DOH,
UP-PGH National
Study, 2000)
DOH
Administrative
Order 2005:0006
VIA as Primary
Screening Tool for the
Philippines
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VIA
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• Looking at the cervix to detect abnormalities after applying dilute (3-
5%) acetic acid
(vinegar)
• Acetic acid enhances and marks a precancerous lesion or cancer by turning it to a whitish hue (acetowhite change).
Normal
VIA positive lesion
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Why Use VIA in Low-Resource
Settings?
Pap smears are usually not widely available in lowresource settings
Testing for the presence of HPV is available only on a very limited basis
VIA appears to be at least as effective as Pap smears in identifying women with precancer or cancer
VIA-based cervical cancer screening involves fewer logistic and technical requirements than Pap smear based screening
Clinical decisions can be made immediately
Less patients are lost to follow up because it utilizes a
Single Visit Approach
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How Does VIA Work?
Counseling about the procedure
Examination by a trained professional
A speculum is inserted into the vagina
3-5% acetic acid (vinegar) is applied to
The cervix is inspected using the naked indicate a treatable precancerous lesion
Any acetowhite changes are noticeable acetic acid
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TESTING TREATMENT
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24
COUNSELING
+
SCREENING
+
=
TREATMENT
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Cryotherapy Unit
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Treating Women with
Unconfirmed Disease
Because of low morbidity associated with cryotherapy, treatment of all women with VIA-positive result may be cost-effective by preventing disease from progressing to cervical cancer
In many settings, additional testing is not available or easily accessed
The inconvenience to women of returning for additional visits often results in loss to follow-up
Cryotherapy has the potential to significantly reduce the probability of developing cancer or precancerous lesions
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Low morbidity and complications associated with cryotherapy
Cryotherapy is being used to treat cervicitis and other
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Examination of the female patient
Includes:
• Observation of the external genitalia.
• Observation of the cervix and vagina through a speculum.
• Palpation of the cervix, uterus, and ovarian areas.
• Sometimes rectal examination.
Examination of the female patient
Demonstrate
Privacy
Explain procedure
Answer questions
consent
THE CERVIX
SIZE AND SHAPE OF THE CERVIX
The cervix is the opening of the uterus.
It is cylindrical in shape and is normally 3–4 cm long and 2.5–3.5 cm in diameter.
The external os of the cervix opens into the vagina.
The internal os is the point at which the cervix and uterus meet, above the vagina.
Parts of the cervix
Ectocervix—exterior to the external os and readily visible during speculum exam.
Endocervix—the portion above the external os and not easily seen.
Endocervical canal— traverses the
Endocervix, connects the uterine cavity with
the vagina; extends from the internal to the external os.
External cervical os
The cervix and the external os vary in size and shape depending on the woman’s age, parity, pregnancy, and hormonal status:
Small, round pinhole in the prepubescent girl or nulliparous woman.
Can be a large, irregularly shaped, gaping slit in parous women.
External cervical os
Nulliparous Parous
Speculum examination & visualization of the cervix
Composition of the cervix
The cervix is composed of dense, fibromuscular connective tissue.
It is covered by two types of epithelium:
• Stratified squamous epithelium (usually covering large areas of the ectocervix).
• Columnar epithelium (covers the endocervix and
may also be visible on the ectocervix).
The two kinds of epithelium meet at the squamocolumnar junction (SCJ).
Squamocolumnar junction (SCJ)
The SCJ is the place where the squamous and columnar epithelia meet.
It often appears as a sharp line of demarcation with a slight difference in height between the two kinds of epithelium.
Squamous metaplasia
Metaplasia refers to the change or replacement of one type of cell by another.
Squamous metaplasia is a physiologic process that occurs on the cervix—the columnar cells on the side of the SCJ closest to the os are gradually replaced with squamous cells.
This process results from the exposure of the columnar cells to the acid environment of the vagina.
Area of T-zone
Most susceptible to carcinogens
The cervix
Effect of estrogen
Cervical anatomy is influenced by estrogen—the location of the SCJ changes throughout a woman’s life in response to changes in estrogen levels.
As a result of increased estrogen levels (menarche, oral contraceptive use, pregnancy):
Cervix swells and enlarges.
Eversion of the endocervical epithelium out onto the ectocervix occurs, pushing the SCJ away from the os, making it easier to see.
As a woman ages, the SCJ retreats inward toward the internal os, making it more difficult to see.
Age Related Changes in the Cervix:
Puberty – Reproductive Years
Increasing levels of estrogen and progesterone
Columnar cells at the SCJ gradually transform into squamous cells (SQUAMOUS METAPLASIA)
Transformation Zone-different stages of squamous metaplasia os
Squamous cells
Transformation Zone(T-zone)
NEW SQUAMOCOLUMNAR
JUNCTION
ORIGINAL SQUAMOCOLUMNAR
JUNCTION
Columnar cells
Chapter 3: Pathophysiology of Cervical
Cancer
Transformation zone
The transformation zone is the area on the cervix between the original SCJ and the new SCJ.
The TZ is covered by metaplastic squamous
epithelium—squamous epithelium that has replaced the columnar epithelium that existed in that area.
Cervix at Puberty
Cervix during the
Reproductive Years
Postmenopausal cervix
The maturation or development of the squamous epithelium depends on the hormone estrogen.
In postmenopausal women, the multiple layers do not accumulate, and the squamous epithelium thins, becomes atrophic, looks pale, and is susceptible to trauma.
Mature squamous cells now cover nearly whole face of cervix
Cervix at
Menopause
Area of T-zone
Most susceptible to carcinogens
Puberty
Reproductive
Menopause
VIA Questions
49
Question 1: Is the cervix suspicious for cancer?
Question 2: Is the Squamocolumnar junction visible?
Question 3: Is the cervix VIA-positive or VIA-negative?
Question 4: Point to the acetowhite lesions in the cervix.
Question 5: Is the patient a good candidate for cryotherapy?
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