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MANAGEMENT OF THE
ABNORMAL PAP SMEAR
2001 Bethesda System
Squamous Cell
•
Atypical squamous cells (ASC)
–
Of undetermined significance (ASC-US)
–
Cannot exclude HSIL (ASC-H)
•
Low-grade squamous intraepithelial lesions (LSIL)
–
Encompassing human papillomavirus (HPV), mild dysplasia, and cervical
intraepithelial neoplasia (CIN) 1
•
High-grade squamous intraepithelial lesions (HSIL)
–
Encompassing moderate and severe dysplasia, carcinoma in situ, CIN 2,
and CIN 3
•
Squamous Cell carcinoma
Glandular Cell
•
Atypical glandular cells (AGC) (specify endocervical, endometrial, or not otherwise
specified)
•
Atypical glandular cells, favor neoplastic (specify endocervical or not otherwise
specified)
•
Endocervical adenocarcinoma in situ (AIS)
•
Adenocarcinoma
THE BAD NEWS
• HPV is VERY COMMON, occurring at
least once over a 3-year period in 60% of
young women
• Lifetime cumulative risk is at least 80%
• The longer HPV is present and the older
the patient, the greater the risk of CIN
• Smoking DOUBLES the risk of
progression to CIN 3 in HPV positive
patients
THE GOOD NEWS
• Vast majority clear the virus or suppress it
to levels not associated w/ CIN 2/3+, and
for most women this occurs promptly
• The duration of HPV positivity is shorter
and the likelihood of clearance is higher in
younger women
• Only 1 in 10 to 1 in 30 HPV infections are
associated w/ abnormal cervical cytology
MORE GOOD NEWS
• Only 15% of women w/ negative cytology
reports and positive HPV will have
abnormal cytology within 5 years
• The risk of cervical cancer in women who
do not harbor oncogenic HPV is extremely
low
• The time course from CIN 3 to invasive
cancer averages between 8.1 and 12.6
years
STILL MORE GOOD NEWS
• Likelihood of regression to normal:
– CIN 1: 60%
– CIN 2: 40%
TYPE OF TESTING
• Cytology vs. Cytology + HPV testing
– Cytology alone low sensitivity
– Cytology + HPV testing much higher
sensitivity
– HPV testing especially helpful in patients > 30
years old
Colposcopy
• Always biopsy any visible lesion
• Up to 10% of lesions more sever than
anticipated
Cytology normal/HPV positive
• If combined testing is normal, repeat
combined testing only every 3 years
• If pap normal and HPV positive repeat pap
in 6-12 months, then colposcopy if still
positive
• ASC - same
Atypical Squamous Cells
•
•
•
•
Most commonly reported abnormality
Risk of cancer 0.1-0.2%
Risk of CIN 2/3+ 6.4%-11.9%
Have the sample HPV tested
– If positive, refer for colposcopy (15-27%
chance of CIN 2/3+)
– If negative, repeat cytology in 1 year (less
than 2% chance of CIN 2/3+)
• Exception: adolescent patients
Low Grade SIL
• Second most common result
• 83% test positive for high-risk HPV
• 15-30% risk of CIN 2/3+ at initial
colposcopy
• Recommendation: colposcopy
• Exception: adolescent? Clearance
high/cancer risk low
ASC-H
• HPV in up to 86%
• CIN 2/3+ in 24-94%
• How does this category differ from HSIL?
– Colpo normal? -> repeat cytology vs. excision
• 30+ year old patient
– HPV testing makes sense as rate of positivity
is much lower
ASC HPV +/ASC-H/LSIL
• If colposcopy normal:
– Repeat cytology in 6 and 12 months or
– HPV testing in 12 months
• If repeat testing is again abnormal (i.e.
ASC or higher or + HPV) colposcopy
should be repeated
HSIL
• 70% + CIN 2/3
• 1-2% invasive cancer
• Always perform colposcopy
– Endocervical assessment (nonpregnant)
– Entire vagina should be examined
• LEEP at colposcopy may be considered
What if HSIL colposcopy results are
CIN 1 or less?
• Review of histology and cytology and/or
• Excision
• Exception: adolescents
– Since the risk of invasive cancer is still
extremely low, colposcopy and cytology tests
may be repeated at 4-6 months as long as the
colposcopy results are adequate and the
endocervical curettage is negative
If cervical cytology is AGC or AIS
• The most common significant lesions
associated w/ AGC are actually squamous
• Management should include colposcopy
and endocervical sampling
– Age 35 and older: include endometrial
sampling
– Less than 35 if: morbidly obese,
oligomenorrhea, abnormal uterine bleeding
Atypical Endometrial Cells
• Always perform endometrial sampling
• If endometrial sampling is negative ->
colposcopy w/endocervical sampling
When should endocervical
sampling be done?
• Unsatisfactory colposcopy
• Ablative therapy contemplated
• Should be considered in: ASC-H, HSIL,
AGC or AIS
– May add 5-9% to CIN2/3+ diagnosis
• NOT in the pregnant patient
Initial evaluation of AGC/AIS
negative
• AGC-NOS: follow-up endocervical
sampling at 6 month intervals (x4)
• Alternative: Test for HPV. If negative may
repeat cytology and endocervical sampling
at one year
• AGC-favor dysplasia or AIS OR a second
AGC-NOS: EXCISION (cold knife
conization better than LEEP)
What you see is NOT what you get
• Colposcopic impression of CIN1 correct
only 43% of the time
• Another study showed women with LSIL
and colposcopic appearance of CIN1 had
CIN 2 or CIN 3 21% of the time after
excision
• Therefore: any visible lesion should be
biopsied
How should CIN 1 be managed?
• For most women: observation
– Especially the younger patient
• Two cytology screenings 6 months apart
CIN 2 and CIN 3 Management
• 40% of CIN 2 regresses over 2 years
• CIN 3 regression: rare
• Immediate treatment is recommended
– Exception: adolescent with CIN 2
• Spontaneous clearance more likely
• Risk of cancer approaches zero
Is excision or ablation better?
• Laser, LEEP, cryotherapy: all the same
• Perform endocervical sampling if ablation
is planned
• Do not perform ablation if dysplasia on
endocervical curettage
Management of AIS
• Excision required: Cold knife conization (CKC)
is preferred:
– Endocervical sampling w/ the CKC is more predictive
of residual disease
• LEEP is associated with an increase in the rate
of positive margins and is not recommended
• If margins are positive CKC should be repeated
– Residual AIS in as many as 80%
Management of AIS
• If margins are negative: risk of residual
AIS (26%) and invasive cancer (1.9%)
– Therefore hysterectomy is recommended
when fertility is no longer desired
– If fertility is desired: follow w/ sampling every
6 months
• Hysterectomy is not appropriate until
invasive cancer has been ruled out
Follow-up after treatment for CIN
• For CIN 1: Cytology at 6 and 12 months
or HPV testing at 12 months is reasonable
• For CIN 2/3: Cytology 3-4 times at 6
month intervals or a single Pap + HPV at 6
months. Then annual screening
• Positive margins may be treated w/
reexcision, but know that 84% remain
disease free WITHOUT reexcision at five
year follow-up
Care and follow-up during/after
pregnancy
• Only the diagnosis of invasive cancer alters
management
• Colposcopy should have as its primary goal the
exclusion of invasive cancer
• ASC or LSIL: colposcopy during pregnancy or 6-12
weeks postpartum
• Higher grade test results: colposcopy without
endocervical sampling. Biopsy only if colposcopic
appearance consistent w/ CIN 3, AIS, or cancer
• Repeat colposcopy each trimester w/ biopsy only if
progression of disease is suggested or cytology is
suggestive of invasive cancer
Last Thing
• What if the cytology report states “No
endocervical cells”?
– May repeat in 1 year if routine testing
– Repeat soon if for specific indication