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Cervical Cancer & Pap
Smears
E.Naghshineh MD
Epidemiology
• 16,000 cases / year
• Incidence  but mortality from
cervical cancer  over the past 50
years
• Cervical CA is still the 7th most
common cancer in females and the
8th most common cause of death
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Etiology
•
Human Papiloma Virus (HPV)
+ an unidentified co-carcinogen
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Risk Factors
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Multiple sexual partners (> 1)
Promiscuous partner
Age of first intercourse experience
Early childbearing
Prior STDs (HSV II, genital warts, vaginal infections)
Cigarette Smoking
Oral Contraceptive usage
Intrauterine exposure to DES
Immunodeficiency
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Age of Onset
• Carcinoma In-Stiu (CIS)
30 years
• Cervical Intraepithelial Neoplasia (CIN) 35 years
• Invasive Cervical Cancer
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45 years
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Histological Types
• Squamous Cell Carcinoma 80-95%
• Adenocarcinoma
5-20%
• Other: Clear cell, sarcomas
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Symptoms
• CIN: Asymptomatic
• Invasive Cancer
– No classic presentation
– May present with abnormal vaginal
bleeding
– May present with postcoital bleeding
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Physical Exam
• CIN
– Cervix appears normal to general inspection
• Invasive Cancer
– Exophytic growth seen on cervix
– Growth: Cauliflower-like, friable, deeply
ulcerated
• Advanced Cancer
– Pelvic Masses Palpable
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Metastasis
• Morbidity and Mortality associated
with regional spread of the cancer
• Spreads to pelvic nodes, ureters,
bladder, rectum.
• Dangerous when cancer blocks
ureters resulting in uremia --> death
• Hematogenous spread- uncommon
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Pathogenesis
• Site where squamous epithelium of vagina
meets columnar epithelium of endocervix
known as squamocolumnar junction (SCJ)
• Before puberty: SCJ located just inside the
cervical os
• At puberty, increasing levels of estrogen lead
to squamous metaplasia of columnar epithelium
to squamous epithelium
• Results in repositioning of the SCJ further
towards the uterus
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Pathogenesis (2)
• Region between the old and new SCJs known as
the transformation zone
• Transformation zone is the site of 95% of the
cervical cancer development
• Since zone is located within the cervical os,
unable to be viewed during routine pelvic exam
• Exposure of transformation zone to carcinogens
begins 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
transformation zone
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Human Papiloma Virus (HPV)
• Certain types of HPV are responsible
for genital warts, others for
dysplasia/cancer
• HPV Types 6 & 11
– associated with development of genital warts
• Types
16,18,31,33,35,39,45,51,52,56,58
– associated with development of
dysplasia/cancer
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Pap Smears
• Strong sensitivity and specificity
• Accuracy of Smear Requires
– adequate sample
– presence of enough inflamation and
dysplasia
– quick fixation of specimen to glass slide
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When to Get Pap Smears?
• ACOG Recommendations
– 1st Pap Smear at age when patient
becomes sexually active (or by age 18)
– Yearly pap smears thereafter
• Others contend that monogamous
women with no history of abnormal
pap smears can have them done every
3 years
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Performing Pap Smear
• Patient asked to lie on her back at edge of exam
table with feet in stirrups
• Metal or plastic speculum is inserted into vagina to
expand the wall of vagina to enable access to cervix
• Cells are collected using cotton swab, wooden spatula,
or cervical brush and smeared onto glass slide
• Preservative sprayed to prevent cells from drying
and artifacts from forming
• Slide evaluated by lab technician who looks for
abnormalities in the 50,000 to 300,000 cells on slide
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Pap Smear Classification
Systems
• The Class System (I to V)
• The CIN System (CIN I to III)
– characterizes the degree of cellular
abnormalities
• The SIL System (Bethesda System)
– Lesions characterized as LGSIL or HGSIL
– Presence of HPV noted
– This scheme is most widely used system
these days
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Evaluating the Pap Smear
• First, the smear is evaluated for
adequacy of sample
• Secondly the sample is categorized
as “normal” or “other”
• Lastly, all sample categorized as
“other” are further specified as
infection, inflammation, or various
stages of cancer
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What to Inform Patients Prior
to Obtaining Pap Smear?
• No douching or usage of vaginal
medications, lubricants, or spermicides
within 2-3 days of exam (these
products may hide abnormal cells)
• Schedule Pap Smear between days 1216 of menstrual cycle, if possible
• Abstain from intercourse 1-2 days
prior to smear
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Pitfalls of Diagnosing Cervical
Cancer
• 30% of cases of cervical cancer are missed
due to errors interpreting results of pap
smears
• Ways of Improving Pap Smears
– rescreen portions of slide deemed negative
to reduce false-negatives
– new liquid smears may be have higher
sensitivty and specificity
– usage of computerized devices to analyze
smear (PAPNET, VIRAPAP)
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Improving Access to Pap
Smears
• 50% of patients who die of cervical
cancer have never had a Pap Smear
• Uninsured, minorities, older patients
and those who live in rural areas have
limited access to Pap Smears
• These groups must be targeted to
further reduce rates of cervical
cancer in the US
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Precursor Lesions
• Reason for thorough classification schemes
for intraepithelial lesions is to determine the
likelihood of such lesions progressing to overt
cancer
• Usual progression from mild dysplasia to
overt cancer takes 7-8 years
• Precursor lesions characterized as mild
dysplasia have 65% chance of spontaneously
regressing, 20% chance of remaining the
same, 15% chance of worsening
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Precursor Lesions (2)
• Unfortunately, we are unable to predict
with much accuracy, which lesions will
regress and which will worsen over time
• For this reason, ACOG recommends any
patient with a mildly abnormal smear
undergo further evaluation with culposcopy
and/or biopsy
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Culposcopy
• Culposcope: A stereomicroscope that
enables investigators to examine areas of
dysplasia and select best sites to biopsy
• device has green filter that helps identify
presence of blood vessels (an ominous sign)
• Before culposcopy, cervix coated with
acetic acid which enhances presence of
dysplasia
• Key to culposcopy is complete visualization
of transformation zone
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Cone Biopsy
• Reasons for Performing Cone Biopsy
– Investigator is unable to visualize the entire
transformation zone
– Endocervical curretage shows dysplastic
changes
– Results of Pap Smear are remarkably different
than results from culposcopy
• Cone biopsy is a minor surgical
procedure to further investigate the
transformation zone
• Performed using a scalpel or laser
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Treatment of CIN
• Most effective treatment is excision
of precursor lesions
• Ways to Remove Lesions
– Cryocautery- freezing, thawing, & refreezing
lesion
– Culposcopic Laser Therapy- more accurate,
capable of removing low and high grade lesions
– Excisional Biopsy- performed on low grade
lesion
• Always schedule follow-up Pap Smears
to assure lesions have not returned
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Managing Cervical Cancer
• All visible lesions should be biopsied
• Lesions must be properly staged to determine
whether cancer has spread and help determine
therapeutic approach
• Cervical Cancer spreads by lymphatics or direct
invasion
• Lymphatic Spread:
– Cervical/paracervical nodes  regional nodes  deep
pelvic nodes
– Direct spread: To bladder, vagina, parametria, rectum
– CT Scan helpful in assessing cancer that has spread
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Treatment of Invasive Cervical
Cancer
• Option 1: Surgery
– Useful in patients with Stage I and II
cancer
– Radical hysterectomy is procedure of choice
for overt cancer
– When performing surgery, spare ovaries so
they can continue to manufacture estrogen
– Potential pitfalls of surgery: hemorrhage,
damage to nerves supplying bladder,
formation of fistula
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Treatment of Cervical
Cancer
• Option 2: Radiation
– Reserved for poor surgical candidates or
patients with advanced disease
– Problems with radiation- infertility,
radiation cystitis, fibrosis
– Usually ineffective in patients with
recurrent cervical cancer
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Prognosis
• Patients with CIS and cancer limited
to cervix- cure rate 90-100%
• Patients with advanced cervical
cancer- cure rate is 25-50%
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Reasons for Such Good
Prognosis for Cervical
Cancer
• Presence of an easily identifiable
precursor lesion
• Slow progression of cancer
• Access to cheap non-invasive diagnostic
tools (Pap Smears and Culposcopy)
• Simple and effective treatments
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