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Grand Rounds / Articles

Management of the Abnormal Pap Smear

Dr. E. Brydon, Practicing Gynecological Oncologist, Regina

This article covers the recommended management of abnormal pap smears (including ASCUS and HSIN). Questions concerning the first abnormal smear, second abnormal smear, and the various grades of CIN will be answered.

1. When a pap smear is reported as abnormal, will I be given any recommendation or direction as to what should be done?

The Prevention Program for Cervical Cancer (PPCC) has met with cytopathologists and cytotechnologists as well as with concerned family doctors and colposcopists to discuss this. The decision was to offer a suggestion as to management for each abnormal pap smear. The clinician has discretion as to whether or not to follow the suggestion, as the clinician is the one who understands the clinical situation. This may help to determine the appropriate management for the abnormal smear.

2. When a pap smear returns showing ASCUS, what is the usual recommended management?

ASCUS stands for "Atypical Squamous Cells of Undetermined Significance". This designation means that the smear showed cells that were not typical squamo-columnar cervical cells or endocervical glandular cells. However, the abnormality is not sufficient to constitute "dysplasia." The management is to try to discover if the abnormality is "significant" by seeing what happens over time. If the lesion is due to dysplasia, it may clear up spontaneously due to the host normal immune defense system or it may persist and show itself again as an ASCUS pap smear, or it may progress into obvious dysplasia. Regardless, nothing needs to be done urgently.

A re-evaluation in 6 months by pap smear is sufficient.

3. What is the role of HPV testing in the presence of an ASCUS pap smear?

If we were able to test for HPV presence at the time of an ASCUS pap smear, we would be able to tell if the abnormality was related to the presence of this virus, and a possible source of future dysplasia. If HPV is not present then the abnormality is not "dysplastic" and therefore the patient can be reassured that more intensive monitoring is not necessary. However, we do not have the ability to test for HPV either easily or economically at this time.

4. What is the recommended management if the ASCUS pap smear shows up for a second time, or recurs after an interval of normal Pap smears?

If an ASCUS pap smear occurs again at the time of the repeat smear, it may well represent a dysplastic lesion that is just not being seen adequately in the specimen obtained. For this reason, it is recommended that persistent ASCUS pap smears be evaluated by colposcopy. A referral to Colposcopy should be made.

If the ASCUS pap smear appears after an interval of normal pap smears, clinical judgment is required. If the previous pap smears have been of good quality, and there have been several (>2) normals in the interim, if the patient has no history of previous episodes of dysplasia, perhaps a repeat smear in 6 months is adequate.

If the patient is post-menopausal, perhaps the ASCUS is due to changes of estrogen deficiency. If this is possible, the recommendation is to pre-treat the vaginal epithelium with estrogen: premarin vaginal cream, 2 gm at hs for the two weeks prior to repeating the pap smear, but not the night immediately prior to the office appointment to repeat the pap!

If the patient has a previous history of dysplasia, if the patient has not had pap smears for several years, either because of poor compliance, or because of the new recommendations of the screening program, then a repeat pap smear in six months is recommended.

5. What is the recommended management for Low Grade Squamous Intraepithelial Lesion, LSIL pap smears?

If this is the first pap smear showing LSIL, the recommendation is to repeat it again in six months. The LSIL lesion is a sign of dysplasia due to HPV infection, but it is mild and usually transient. This is especially true for women under the age of 25 where the transformation zone of the cervix is very prone to contracting HPV virus infections, but where it also frequently disappears, on average in eight months or so.

If this is the second time that LSIL has appeared, it is recommended that the patient be referred for colposcopy for evaluation to see if a more severe lesion is not present. Persistence of LSIL can be due to just that - persistence, but it may also represent a more severe lesion, a progression of disease that is unrecognized in the second pap smear.

6. What is the recommended management for the High Grade Squamous Intraepithelial Lesion, HSIL?

HSIL suggests that the there is a lesion on the cervix of high grade, possibly precancerous. These lesions should all be referred fro colposcopy.

If a lesion is seen on the cervix at the time of a pap smear, the pap smear should still be taken, but a referral for further assessment for the cervical lesion should be made regardless of the pap smear result. Although perhaps surprising, cervical cancer can return on pap smear as ASCUS or even as mild dysplasia. It is important to trust your clinical judgment about the appearance of the cervix regardless of the pap smear result.

7. What is the management for Atypical Squamous Cells, Suggestive of High Grade ASC-H?

This designation is ominous, perhaps more ominous than the HSIL category. Urgent referral for colposcopy is recommended. More cancer has been diagnosed at colposcopy following a pap smear diagnosis of ASC-H than following a pap smear of HSIL.

8. What is the management of Atypical Glandular Cells of Undetermined Significance, AGUS?

AGUS suggests an abnormality of the glandular or columnar cells of the endocervix. Although much less common, the cervix can develop cancer in this area, the adenocarcinoma of the cervix. AGUS may be a precursor of this, or it may also be found in association with squamous cell dysplasia, usually of the more severe types, CIN 2 or 3. For these reasons, this category of pap smear should result in a referral for colposcopy.

9. What is the management of Adenocarcinoma in Situ, ASIS; of (possible) Adenocarcinoma; of (possible) Squamous Cell Carcinoma?

All these categories suggest possible malignancy. Although ASIS is not an actual cancer, it is associated with a high incidence of cancer when investigated. For this reason, any pap smear reported as one of the above, should be investigated urgently.

10. What is the management of the pap smear reported as showing endometrial cells?

The Bethesda 2001 Classification System decided to report the presence of endometrial cells on pap smears as abnormal if the woman was over the age of 40. This decision was based on the possibility of endometrial cancer presenting as shed endometrial cells appearing on the pap smear of a menopausal woman. Obviously, many women over the age of 40 are not menopausal. For this reason, clinical judgment is required. If the pap smear was taken from a pre-menopausal woman, especially near the time of her menses, the finding of endometrial cells is not abnormal and no further follow up is required. If the woman is post-menopausal, then investigation the endometrium should be considered.

11. What is the management of the pap smear showing Atypical Glandular Cells (AGC), whether of endocervical or endometrial origin, or not otherwise specified (NOS)?

The bottom line here is that something is there that shouldn't be there. Perhaps there is an underlying adenocarcinoma of the cervix, or an adenocarcinoma of the uterus, or some other aberration, but these categories mandate further investigation. The atypical endometrial glandular cells are often investigated by office sampling of the endometrium. The atypical endocervical glandular cells will require sampling of the endocervix by cone biopsy of some type.

12. What is the management of the pap smear reported as "No Endocervical or Metaplastic Cells Present"?

This is not an uncommon problem as we all know. It suggests that the transformation zone has not bee sampled. Since this is where the vast majority of problems arise, does this mean that more dysplasia will be missed? Actually, this has never been proved in studies. However, it is a bit concerning to leave these women unscreened for three years, as is possible in the PPCC. For this reason, judgment is needed. It certainly will not be amiss to re-screen these women in a year, rather than in three years.

13. What is the difference between the LSIL category and HPV or CIN 1? Between the HSIL category and CIN 2 or 3?

LSIL is a cytology diagnosis using the Bethesda system. It is used by cytotechnologists and cytopatholgists in reporting pap smears. HPV and CIN 1 are categories used by colposcopists and histologists to describe changes seen in the tissue of the cervix. HSIL is the cytopatholgic designation; CIN 2 and are the histopathologic diagnoses. These have not been amalgamated.