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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