A satisfactory Pap smear will give one of the following results and may provide information on hormonal status:

• Within normal limits
• Benign cellular changes (including reactive or reparative changes)
• Epithelial cell abnormalities, such as atypical squamous cells of undetermined significance (ASCUS), low-grade or high-grade squamous intraepithelial lesions (LSIL or HSIL), squamous cell carcinoma, adenocarcinoma, or atypical glandular cells of undetermined significance (AGUS)
• Other malignancies

These findings are discussed in detail below:

1. Benign cellular changes
2. ASCUS
3. LSIL
4. HSIL
5. AGUS

Benign cellular changes
The management of benign cellular changes depends on the cause. Benign cellular changes include abnormalities identified on the smear that are associated with infection, inflammation, atrophy, radiation, or an intrauterine device. If you can identify the cause of the benign cellular changes, treat the cause and repeat the Pap smear after resolution. Treatment of infection does not change screening frequency. If no cause is found, repeat the Pap smear in 6 months with particular attention to patient factors that may lead to benign cellular changes (Appleby).

Atypical squamous cells of undetermined significance
Appropriate clinical management of ASCUS is more complex. ASCUS indicates cellular changes that exceed reactive or reparative changes but that do not warrant classification as a squamous intrepithelial lesion (Sanfilippo). Unfortunately, criteria for this diagnosis vary among laboratories. To avoid overuse of the designation, the 1992 National Cancer Institute (NCI) Workshop recommended that ASCUS be reported at a rate of up to two to three times the rate of squamous intraepithelial lesions in the population being screened. The Workshop also suggested that ASCUS be qualified by a statement favoring either a reactive or a premalignant or malignant process.

• For ASCUS, not further qualified or favoring a reactive process:
  Serial Pap smears without colposcopy constitute acceptable follow-up. However, the frequency of testing should increase to every 4 to 6 months for 2 years, or until three consecutive smears are negative. All Pap smears during this follow-up period must be reported as "satisfactory for evaluation" (in addition to being normal). Routine screening may resume after this is satisfied. If a second report of ASCUS occurs in the follow-up period, colposcopy is recommended.
• For ASCUS associated with severe inflammation, not further qualified:
  The Pap smear should be repeated in 2 to 3 months or after appropriate treatment of a known causative agent. Empiric antimicrobial therapy is not recommended.
• For ASCUS in a postmenopausal woman:
  The NCI Workshop suggested a course of topical estrogen therapy. Postmenopausal women who are not on hormone replacement therapy may have cellular changes from atrophy that resemble neoplastic changes. If cellular changes persist after an estrogen trial, the patient should be considered for colposcopy.
• For ASCUS in a woman with risk factors:
  Colposcopy should be considered in a woman with ASCUS who may be at higher risk because of a history of abnormal Pap smears, multiple risk factors for cervical cancer, or a history of noncompliance with follow-up visits.
• For ASCUS favoring a neoplastic process:The patient should be managed as if with a diagnosis of LSIL.
• For ASCUS and human papilloma virus (HPV):
  Although not recommended by the 1994 NCI Workshop, HPV testing or cervicography may have a role in risk stratification of women with ASCUS on Pap smear (Kurman).

Low-grade squamous intraepithelial lesions
LSIL may be followed with repeat Pap smears every 4 to 6 months for 2 years if the patient reliably complies with follow-up. Three consecutive normal smears that are satisfactory for evaluation return the patient to routine screening guidelines. Any persistent abnormality requires colposcopy and directed biopsy. Although some physicians use HPV typing and cervicography to identify higher risk patients, this is not generally recommended. Some authorities recommend colposcopy with directed biopsy and endocervical curettage after the first Pap smear that reports LSIL.

Recommendations for the treatment of LSIL are controversial because 6% to 60% of such lesions spontaneously revert to normal. Some progress to a precancerous lesion. The NCI Workshop emphasizes that "routine electroexcision of the transformation zone of nonstaining areas as a method of evaluating a positive Pap smear diagnosed as LSIL or ASCUS is not recommended." Also, ablation or excision should not proceed without histologic confirmation of the diagnosis. If biopsy confirms a low-grade lesion, excision or ablation should be done in patients who may not comply with follow-up. If the entire lesion and the limits of the transformation zone (TZ) are visualized, the NCI states that "the patient can be followed up carefully with no treatment," because so many lesions reverse. Conization is indicated if the entire lesion or TZ cannot be visualized under the colposcope, if endocervical curettage shows abnormal cells, if the Pap smear reports a higher grade lesion than the biopsy, or if invasion may occur (Appleby).

High-grade squamous intraepithelial lesions
A patient with HSIL reported on Pap smear should undergo colposcopy, usually with directed biopsy. Histologically confirmed lesions are excised or ablated in nonpregnant women. If the entire lesion and TZ are not visualized, conization is performed. Recommendations differ for pregnant women with HSIL (O'Leary).

Atypical glandular cells of undetermined significance
Recommendations vary for the management of AGUS, in part because this category includes lesions ranging from exuberant benign reactive changes in endocervical or endometrial cells to endocervical adenocarcinoma in situ. There are two possible origins: the endocervix and the endometrium. As with ASCUS, the NCI suggests further qualification of this diagnosis. Endocervical cells may favor a reactive or neoplastic process, but endometrial cells are not subclassified because of a lack of well-defined criteria. For practical purposes, if AGUS is reported from a cervical sample, colposcopy should be done with endocervical curettage. If the sample is from the endometrium, endometrial biopsy should be done in addition to colposcopy and curettage. Adenocarcinoma in situ prompts evaluation of the endocervical canal, best done by cone biopsy. If the diagnosis of AGUS is unqualified or designated reactive, treatment options range from repeating the smear using a cytobrush, to curettage and hysteroscopy. Persistent reports of AGUS usually necessitate cone biopsy (O'Leary).