Management of Atypical Glandular Cells (AGC) on Pap Smear
The most appropriate management is B. Colposcopy, along with endocervical curettage (ECC) and HPV DNA testing, NOT HPV testing alone. 1
Initial Evaluation Algorithm
All patients with AGC require immediate colposcopy with endocervical curettage (ECC) and HPV DNA testing (if not already performed) as the initial evaluation. 1 This is non-negotiable because:
- AGC is associated with clinically significant lesions in 45% of patients, including CIN, adenocarcinoma in situ (AIS), cervical cancer, and endometrial/ovarian/fallopian tube cancers 1
- 3% to 17% of women with AGC have invasive cancer 1
- HPV DNA testing alone is NOT appropriate for initial triage of AGC 1
- Repeating cervical cytology is NOT appropriate for initial triage of AGC 1
Age-Based Additional Evaluation
Patients <35 years without endometrial cancer risk factors:
- Colposcopy + ECC + HPV DNA testing 1
Patients ≥35 years OR any age with risk factors:
Endometrial cancer risk factors include: 1
- Obesity
- Unopposed estrogen replacement therapy
- Polycystic ovarian syndrome
- Tamoxifen therapy
- Anovulation
- Hereditary nonpolyposis colorectal cancer syndrome (HNPCC)
- Abnormal bleeding
Why Colposcopy is Superior to HPV Testing Alone
Glandular lesions affect areas of the cervix that are harder to sample (endocervical canal), making direct visualization essential. 1 The NCCN explicitly states that HPV DNA testing alone is not appropriate because:
- Cervical cytologic screening methods are less useful for diagnosing AIS 1
- AGC requires tissue diagnosis to rule out invasive disease 1
- Research confirms 19-32% of AGC cases have significant pathology including invasive cancer 3, 4, 5
Subsequent Management Based on Findings
If colposcopy/biopsy reveals CIN I with negative ECC:
- Conservative management with repeat cytology every 6 months until 2 consecutive negatives, OR HPV DNA testing at 12 months 1
If CIN II or III identified:
- LEEP or Cold Knife Conization (CKC) 1
If AIS or "AGC favor neoplasia" identified:
- CKC is preferred over LEEP (LEEP has higher positive margin rates in AIS) 1
- Follow CKC with endometrial sampling 1
- Refer to gynecologic oncologist 1
Critical Pitfalls to Avoid
- Never rely on HPV testing alone for AGC triage - this misses glandular lesions that may be HPV-negative or in hard-to-sample areas 1
- Never repeat cytology as initial management - this delays diagnosis of potentially invasive disease 1
- Never skip endometrial biopsy in patients ≥35 years - 11-12 of 22 malignancies in AGC cases were endometrial cancers in research studies 5, 6
- Do not assume adequate colposcopy rules out disease - approximately 30% of AIS patients have residual disease despite negative margins 1, 7