MANAGEMENT OF ABNORMAL PAP SMEAR RESULTS

• Reduction of risk factors for cervical cancer
• HPV DNA Testing-If liquid based cytology is used, allows for "reflex" testing for HPV if cytology is abnormal
• Note that colposcopy as mentioned below should include endocervical curettage (except in pregnancy) and directed cervical biopsy
• Note that indole-3-carbinol 200-400mg/d, a compound found in cruciferous vegetables (400mg = 1/3 head of cabbage), may increase likelihood of regression of LGSIL and HGSIL (based on a pilot placebo-controlled study of 27 women reported at Soc. Gyn. Onc. 5/99 per FP News 6/1/99)

Based on 2006 concensus guidelines:

I. Atypical Squamous Cells-Undetermined Significance (ASC-US)

1. Usually represents transient HPV infection and resolves without treatmetn
2. In one series of 400 women undergoing colpo, among those with ASCUS paps, 15% had LGSIL and 8% had HGSIL on colpo bx's (Obs. Gyn. 92:356, 1998--AFP)
3. For postmenopausal women with clinical or cytologic evidence of atrophy, may treat with intravaginal estrogen x 4wks (if not contraindicated) and re-pap 1wk after completing is an option
4. For immunosuppressed women including HIV infection (regardless of CD4 count or viral load), consider colposcopy for any ASC-US
5. Per 2006 guidelines (ACOG?), in women < 20yo:
1. No need for HPV testing (doesn't alter management)
2. No difference in management based on immune status
3. Repeat cervical cytology in 1y AND if < HGSIL, cytology again in 1y and if THAT is ASCUS or greater, colposcopy

II. Atypical Squamous Cells-Cannot Exclude HSIL (ASC-H)

1. Prevalence of CIN 2-3 on colposcopic bx is 24-94% (per 2002 guideline document)
2. 2002 guidelines(ACOG?)  recommend:
   1. Colpo for all these women (2006 guidelines concur)
   2. If colpo is normal, review cytology, colpo, and histology results and if no revision of the diagnosis, pap at 6mos & 12mos OR HPV DNA testing at 12mos and if ASC-US or worse on repeat pap OR HPV+, repeat colpo

II. LGSIL

1. 15-30% will have CIN 2-3 on cervical biopsy
2. Most resolve without treatment; some will progress on to high-grade dysplasia (only 3% in 36mos in one prospective study of 187 women 13-22yo with positive HPV DNA tests on cervical specimens and LGSIL at baseline (Lancet 364:1678, 2004--JW)
3. 2002 guidelines (ACOG?) recommend:
   1. Colposcopy initially for all these patients EXCEPT
   1. For postmenopausal or adolescent women, acceptable to either (repeat pap at 6 & 12mos and colpo if ASC-US or worse on either specimen) OR (HPV DNA testing @ 12mos and colpo if positive)
   2. For postmenopausal women with clinical or cytologic evidence of atrophy, may treat with intravaginal estrogen x 4wks (if not contraindicated) and re-pap 1wk after completing is an option; if repeat is normal, re-pap 4-6mos and if still normal, go back to routine intervals; if either abnormal, go to colpo
   2. If colpo shows no CIN, either (repeat pap at 6 & 12mos and colpo if ASC-US or worse on either specimen) OR (HPV DNA testing @ 12mos and colpo if positive)
4. Per 2006 guidelines, for women < 20yo can manage same as ASCUS above
5. 2006 guidelines recomment:
   1. If pregnant and > 20yo, do colposcopy (though may defer till 6wks postpartum)
   2. If postmenopausal, options include reflex HPV testing, repeat cytology at 6mos or 12mos, or colposcopy (see also above from 2002 guidelines)

III. HGSIL

1. Per 2002 guidelines; 70-75% will have CIN 2-3 on cervical biopsy
2. 2002 guidelines recommend:
   1. Colposcopy with endocervical assessment
   2. If colpo normal or shows only CIN 1 on bx, review cytology, colposcopy, and histology results; if no change on this review, do a diagnostic excisional procedure (if nonpregnant) or "a colposcopic reevaluation with endocervical assessment is acceptable in special circumstances"; for "young women" can do repeat colpo + cytology Q4-6mos x 1y rather than initially doing the diagnostic excisional procedure
   3. If colposcopy suggets a high-grade lesion, can use a diagnostic excisional procedure as the next step
   4. Some special recommendations are made for pregnancy (see guidelines for details)
3. 2006 guidelines say colposcopy if < 20yo; otherwise options include LEEP or colposcopy w/endocervical assessment

IV. Glandular cell abnormalities

1. Atypical glandular cells Not Otherwise Specified (AGC-NOS)
   1. 9-54% of these pts have biopsy-confirmed CIN per 2002 guidelines
2. Atypical glandular cells, favor neoplasia (AGC-Favor Neoplasia)
   1. 27-95% of these pts have biopsy-confirmed CIN per 2002 guidelines
3. Recommended approach per 2002 guidelines for AGC, AGC-Favor Neoplasia, and Adenocarcinoma in situ (AIS) (2006 guidelines basically concur)
   1. Initial workup
      1. Colposcopy with endocervical sampling and HPV testing
      2. Endometrial sampling first if the AGC result indicates that the cells are endometrial
      3. Otherwise endometrial sampling concurrently with colpo if pts > 35yo or has unexplained vaginal bleeding or or other indication of risk for endometrial hyperplasia or carcinoma
   2. If initial workup doesn't reveal invasive disease:
      1. If cytologic dx was AGC-Favor Neoplasia or AIS, do a diagnostic excisional procedure (cold-knife cone biopsy is preferred)
      2. If cytologic dx was AGC-NOS, repeat cytologic testing Q4-6mos until 4 consecutive normal results, then return to routine schedule; if abnormal results ensue, go to colpo or refer to "a clinician experienced in the management of complex cytological situations"
4. Consider extrauterine source for AGUS if no source found with above-mentioned diagnostic efforts (ovary, colon, breast)

V. Other abnormalities

1. Hyperkeratosis & parakeratosis: a reactive mechanism to physical, chemical, or inflammatory trauma; rarely ass'd w/sig. disease. If not read as ASCUS, can repeat pap in 6mos and if persists, do colpo or an "intermediate triage" technique (see above)
2. Inflammation: "The presence of background inflammatory cells in an otherwise normal smear is not an indication for further evaluation" (AFP rvw.), though may render the smear unsatisfactory for interpretation. They do recommend checking w/wet mount & treating yeast, BV, etc. if positive but if negative, the cervix appears grossly nl, and pap nl except for inflammation, can just repeat pap in 6-12mos (repeating in < 6mos sig. increases chances of getting an ASCUS on repeat smear). Persistent inflammation can be a sign of HGSIL or even invasive Ca, so should do colpo in that instance.
3. Absence of endocervical cells: unclear significance. A retrospective study of 18,000 pap smears in women who had 2 or more paps over a 4y period found no sig. diff. in incidence of abnormal paps subsequent to a normal smear in women w/ and w/o endocervical cells on the initial smear; those w/o endocervical cells initially tended to lack endocervical cells on subsequent smears (Acta Cytol. 30:258, 1986, cited in AFP rvw); AFP rvw concludes that if routine pap has no endocervical cells but o/w nl and pt has no h/o abnl paps, can wait until the next annual exam to perform.
4. Endometrial cells (except in 1st 2 weeks of menstrual cycle)-should do endometrial bx and/or D & C / hysteroscopy

(Sources include: Wright TC Jr et al. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol 2007 Oct; 197:346 ; these are jointly from: National Institutes of Health, the American Cancer Society, and the American College of Obstetricians and Gynecologists; Core Content Review of Family Medicine, 2012)