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Managing ASCUS and AGUS Pap Smears

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Managing ASCUS and AGUS Pap Smears Managing ASCUS and AGUS Pap smears More than half of all high-grade lesions are preceded by an ASCUS or AGUS Pap smear. By adopting definitive management strategies for these types of abnormal cytology, Ob/Gyns have a unique opportunity to prevent cervical cancer. BY MELVIN V. GERBIE, MD ith the newest iteration of the While the terminology has been tightened, WBethesda System in place—the cytologic laboratories still lack uniformity in second revision in 10 years—the their reporting of atypical cells. When clinician is again asked to learn new classi- reviewed by consulting cytopathologists, a fications of cervical cytology and significant percentage of these the attendant management proto- Melvin V. Gerbie, MD smears are reclassified as normal. cols. One purpose of the new But, since clinical management system is to eliminate the confu- decisions are based on the origi- sion and variability of the previ- nal cytology, there is the possi- ous Papanicolaou (Pap) Class II bility of both false-negative and smear and the CIN Class 2R false-positive Pap test results. smear, both of which acted as Consequently, patients are either “hedges” to let the clinician subjected to more active man- decide on management.1 agement or a delay in diagnosing Under the newest system, atypi- a serious abnormality. cal squamous cells are subclassi- Never treat a Add managed care to the fied into ASC-US (undetermined equation, and more difficulties patient based significance) and ASC-H (cannot arise. Currently, it is unusual for exclude high-grade dysplasia). solely on an a gynecologist to choose his or Atypical glandular cells of undeter- abnormal smear. her cytologic laboratory or mined significance (AGUS) also ••• pathologist. Instead, these des- have been subclassified. The rea- ignations are frequently deter- son: To create specific readings of mined by the patient’s insurance cell changes, as atypical cells often company, reducing a clinician’s are seen prior to dysplasia. In fact, in a 1998 ability to consult with a cytopathologist with Kaiser review, 52% of high-grade lesions whom he or she is acquainted. Despite these were preceded by either a smear of ASCUS obstacles, the recent FDA approval of liquid- or atypical glandular cells of undetermined based cytology and human Papillomavirus significant (AGUS). The most frequent pre- (HPV) testing has helped to augment patient cursor smear was ASCUS (43.6%).2 care and management. With these new tech- nologies and others on the way, it is impor- Dr. Gerbie is section chief of gynecology at tant to understand the management algo- Northwestern University Medical School in rithms available. Following are my prefer- Chicago, Ill. ences in evaluating and treating patients 34 OBG MANAGEMENT • MARCH 2002 ASCUS and AGUS Paps: management protocols Liquid-based cytology AGUS ASCUS Women Women under 40 over 40* Repeat Pap in 3 months Colposcopy, ECC, Colposcopy and endometrial and ECC sampling Abnormal Normal Abnormal Normal Abnormal Normal Colposcopy Repeat Pap in 3 months LEEP or Repeat Pap in LEEP, cone, or Repeat Pap in cone biopsy 3 months hysterectomy 3 months Abnormal Normal Abnormal Normal Abnormal Normal Abnormal Normal Repeat LEEP, cone, Repeat Pap Colposcopy Return to Colposcopy, Repeat Pap in Colposcopy, in 3 months annual Paps Pap in or ECC LEEP, or cone 3-6 months LEEP, or cone 6 months *Women with endometrial cell abnormalities; Postmenopausal women with normal endometrial cells not receiving HRT. with either ASCUS or AGUS cytology. the patient to the usual cycle of yearly Paps.) When colposcopy is unsatisfactory, Managing ASCUS an ECC is indicated. If the ECC is negative, Use liquid-based cytology for those the patient is followed by a repeat smear in patients who have ASCUS or AGUS smears 6 months. Administering vaginal estrogen or any cellular abnormality including previ- may be helpful in the postmenopausal ous dysplasia; a clinically abnormal cervix; patient, as it promotes epithelial maturation or a history of postcoital bleeding; and /or since immature cells may be confused with heavy vaginal discharge. While this collec- atypical squamous cells. tion method can be used in the presence of On the other hand, when ASC-H is found, a small amount of menstrual blood, do not schedule an immediate colposcopy. In addi- take the smear if there is normal or heavy tion, colposcope all patients who are consid- menstrual bleeding. Collect the specimen ered at high risk for cervical cancer, including using either a spatula and endobrush or women with HIV or renal transplants.3 cytobrush (paint brush). Perform a repeat Pap smear in 3 months Managing AGUS in patients who have ASC-US cytology but AGUS is another borderline classification. no previous abnormal history. I do not treat Although the subclassifications have been nonspecific inflammation. Perform a col- reduced from the previous Bethesda System poscopy when a second ASC-US smear is (refer to www.bethesda2001.cancer.gov for reported. If the colposcopy is satisfactory a complete breakdown of the subclassifica- and no abnormality is seen, do not perform tions), there are still management decisions an endocervical curettage (ECC) or cervical that have to be made. Fortunately, the most biopsy. Repeat the Pap smear in 6 months. common histologic abnormality found is (Bear in mind that follow-up smears should ASCUS, not AGUS.4 Furthermore, lesions be negative at least twice before returning associated with AGUS are usually found 36 OBG MANAGEMENT • MARCH 2002 near the external os, not high in the endo- Key points cervix. Colposcopically, subtle changes in endocervical glandular cells may represent ■ In a 1998 Kaiser review, 52% of high-grade normal metaplasia, atypical metaplasia, lesions were preceded by either a smear of microglandular hyperplasia, intraepithelial ASCUS or AGUS. neoplasia, or even early invasive adenocar- ■ The most common histologic abnormality cinoma.5 Therefore, clinicians are obligated found is ASCUS, not AGUS. to sample more tissue sites. ■ Under the 2001 Bethesda System, atypical In contrast to ASCUS, neither observation squamous cells are subclassified into ASC-US nor a repeat Pap smear is an option because (undetermined significance) and ASC-H (can- the potential for abnormalities is much high- not exclude high-grade dysplasia.) er in the AGUS smear. Management is based on the AGUS subclassification (if given) and the patient’s age. ed patients to be separated into low- and Perform a colposcopy and endocervical high-risk groups. However, the value of curettage in women under the age of 40. (In HPV typing appears to be limited to patients contrast to ASCUS management, an ECC is with ASCUS and AGUS Pap smears and the almost mandatory for glandular cell abnor- follow-up of patients with histologically malities since adenocarcinoma, both proven low-grade dysplasias. In these intraepithelial and invasive, do not produce instances, if a patient has a high-risk HPV the visible lesions seen with squamous type, including 16, 18, 31, or 33, she should lesions.) Take endometrial samplings from be referred for colposcopy. Clinical studies the following: patients 40 and older, women are underway to determine the benefit of with endometrial cell abnormalities, and HPV typing in all patients.7 postmenopausal women with normal New technologies aimed at decreasing endometrial cells not receiving any form of the 30% false-negative rate, including com- hormone replacement therapy.6 puterized screening, speculoscopy, and cer- If the colposcopy and evaluation of the vicography, may soon serve to augment endocervix or endometrium, as indicated conventional Pap test results. However, previously, is negative, repeat the smear in more studies are needed to fully evaluate 3 months. If a second AGUS smear is report- their efficacy in cervical cancer screening. ■ ed, repeat colposcopy, loop electrical exci- sion procedure (LEEP), or conization should REFERENCES be performed. However, if colposcopy and 1. National Cancer Institute Workshop. The 1988 Bethesda system for reporting cervical/vaginal cytologic diagnoses. JAMA. 1989;262:931-934. evaluation of the endocervix or endometri- 2. Kinney, WK, et al. Where’s the high-grade neoplasia? The importance um is abnormal, proceed directly to LEEP or of minimally abnormal Papanicolaou diagnoses. Obstet Gynecol. 1998; cone biopsy. Appropriate treatment of 91:973-976. endometrial abnormalities should be indi- 3. Maiman, W, Fructer, RG, Serurer E, et al. Human immunodeficiency vidualized. virus infection and cervical neoplasia. Gynecol Oncol. 1990;38:377-382. 4. Veljovich, DS, Stoler, MH, Andersen, WA, et al. Atypical glandular cells Future screening techniques of undetermined significance. Am J Obstet Gynecol. 1998;179:382-390. 5. Wright, VC. Home Study Course: Summer 2001. Differentiating glandu- Cytology has become much more sophis- lar disorders from their colposcopic mimics. J Lower Genital Tract ticated in the past few years. However, it Disease 5. 2001:189-192. remains a screening test and is still not diag- 6. Cox, NT. ASCCP Practice Guidelines. Management of glandular cell abnormalities in the cervical smear. J Lower Genital Tract Dis 1. nostic. Never treat a patient based solely on 1997:41-45. an abnormal smear. Limit “see and treat” 7. Kaufman R. Is there a role for human Papillomavirus testing in clinical protocols to patients with high-grade cytol- practice? Obstet Gynecol. 2001:98;724-725. ogy confirmed by colposcopy. Currently, HPV testing is being evaluated in many clinical situations. There are more The author reports no financial relationship with any companies whose products are mentioned in this article. than 100 types of this virus, allowing affect- MARCH 2002 • OBG MANAGEMENT 39.
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