MANAGEMENT OF THE ABNORMAL PAP SMEAR

2001 Bethesda SystemSquamous 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 carcinomaGlandular 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