What are the next steps after a Pap smear result shows Atypical Glandular Cells (AGUS)?

Management of Atypical Glandular Cells (AGUS/AGC) on Pap Smear

All patients with atypical glandular cells require immediate colposcopy with endocervical sampling and HPV DNA testing; women ≥35 years or those with endometrial cancer risk factors also need endometrial sampling. 1, 2

Initial Evaluation Algorithm

The following procedures must be performed for all AGC results:

• Colposcopy with directed biopsies of any suspicious lesions after acetic acid application 1, 2
• Endocervical sampling using either endocervical curettage or cytobrush 1, 2
• HPV DNA testing if not already obtained 1, 2

Simply repeating the Pap smear or using reflex HPV testing alone as initial triage is unacceptable for AGC. 1, 3

Age-Based Endometrial Sampling Requirements

For women ≥35 years old:

• Endometrial sampling (biopsy, D&C, or hysteroscopy) is mandatory in addition to cervical evaluation 1, 2
• This recommendation exists because AGC can indicate endometrial pathology in up to 38% of cases, with 3-17% having invasive cancer 1

For women <35 years old:

• Endometrial sampling is required only if risk factors are present 1, 2
• Risk factors include: unexplained vaginal bleeding, chronic anovulation, obesity, unopposed estrogen therapy, polycystic ovarian syndrome, tamoxifen use, or hereditary nonpolyposis colorectal cancer syndrome 1, 2

Clinical Significance

AGC represents only 0.2% of cytologic smears but carries substantial risk 1:

• Up to 38% harbor significant squamous or glandular lesions 1
• CIN is the most common pathology, especially in women <35 years 1
• HPV positivity predicts 20% risk of CIN 3 or cancer 1, 2

Management Based on Initial Findings

If initial evaluation is unremarkable:

• HPV-positive patients: Repeat cytology combined with HPV DNA testing at 6 months 1, 2
• HPV-negative patients: Repeat cytology combined with HPV DNA testing at 12 months 1, 2
• If both tests are negative on reevaluation, annual cytologic testing may resume 1

If CIN is identified (without glandular neoplasia):

• Manage according to standard CIN guidelines based on grade 1, 2

If glandular neoplasia or adenocarcinoma in situ (AIS) is found:

• A diagnostic excisional procedure is mandatory 1, 2
• Cold knife conization is preferred over LEEP for adequate evaluation 1, 2

If AGC is subcategorized as "favor neoplasia" or AIS:

• An excisional procedure may be required for full evaluation even if initial testing is negative 1

Special Populations

Pregnant women:

• Undergo identical initial evaluation except endocervical curettage and endometrial biopsy are contraindicated 2
• Colposcopy and HPV testing should still be performed 2

Critical Pitfalls to Avoid

• Never use repeat cytology alone or reflex HPV testing as the sole initial triage method for AGC—this misses significant disease 1
• Do not skip endometrial sampling in women ≥35 years—endometrial pathology is found in a substantial proportion of these patients 1, 2
• Recognize that liquid-based cytology improves detection of glandular lesions but AGC still requires comprehensive evaluation because glandular abnormalities affect harder-to-sample areas of the endocervical canal 1
• Remember that CIN is actually the most common finding with AGC, not glandular pathology, particularly in younger women 1