In a woman aged 25 years or older with a Pap test showing atypical squamous cells (ASC‑H), atypical glandular cells (AGC), and positive high‑risk HPV, what is the guideline‑recommended management?

Management of Pap Showing Atypical Glandular Cells, Atypical Squamous Cells, and HPV Positive

For a woman aged 25 years or older with both atypical glandular cells (AGC) and atypical squamous cells (ASC-H) on Pap testing with positive high-risk HPV, immediate colposcopy with endocervical sampling is mandatory, and endometrial sampling should be added if the patient is 35 years or older or has risk factors for endometrial cancer. 1

Immediate Diagnostic Workup

The presence of AGC drives the management algorithm because it carries the highest risk of significant pathology:

• Colposcopy with endocervical sampling is required for all AGC cases, regardless of HPV status or concurrent squamous abnormalities. 1
• Endometrial sampling must be performed if the patient is ≥35 years old or if she is younger with unexplained vaginal bleeding or risk factors for endometrial cancer. 1, 2
• Reflex HPV testing or repeat cytology alone is unacceptable as the initial triage for AGC. 1

The concurrent ASC-H finding reinforces the need for immediate colposcopy, as ASC-H carries up to a 50% risk of CIN 2,3. 1

Critical Risk Stratification

The combination of AGC with positive HPV testing carries particularly high risk:

• AGC can indicate significant squamous or glandular lesions up to 38% of the time, despite benign lesions being most common. 1
• HPV positivity with AGC has a high positive predictive value for significant cervical disease, with 20% of women having CIN 3 or cancer on biopsy. 1
• The concurrent ASC-H finding adds additional risk, as 52% of women with ASC-H have underlying CIN 2,3 or worse. 3, 4

Components of the Initial Evaluation

Your colposcopic evaluation must include:

• Visualization of the entire squamocolumnar junction with application of 3-5% acetic acid solution. 5
• Endocervical curettage or cytobrush sampling is mandatory for AGC evaluation. 1
• Colposcopically-directed biopsies of any abnormal areas identified. 5
• Endometrial sampling (endometrial biopsy or dilation and curettage) if age ≥35 years or if risk factors present. 1, 2

Post-Colposcopy Management

If the initial colposcopic evaluation is unremarkable:

• Repeat cytology and HPV testing at 6 months if the initial HPV test was positive. 1
• Repeat cytology and HPV testing at 12 months if the initial HPV test was negative. 1
• Annual cytologic testing may resume only if both HPV testing and cytology are negative on reevaluation. 1

If AGC-favor neoplasia or adenocarcinoma in situ (AIS) was the initial diagnosis:

• An excisional procedure may be required for full evaluation even if initial colposcopy and sampling are negative. 1
• Cold-knife conization is preferred for diagnostic excision in cases of AGC-favor neoplasia or AIS without identified invasive disease. 2

Common Pitfalls to Avoid

• Do not manage this case based solely on the ASC-H component—the AGC finding mandates more aggressive evaluation including endocervical and potentially endometrial sampling. 1
• Do not defer colposcopy in favor of repeat cytology or HPV testing; immediate colposcopy is non-negotiable for AGC. 1
• Do not omit endometrial sampling in women ≥35 years, as 7% of postmenopausal women with benign endometrial cells have significant endometrial pathology. 1
• Do not assume a negative colposcopy rules out disease—if AGC-favor neoplasia or AIS was diagnosed, excisional procedure may still be needed. 1

Age-Specific Considerations

For women aged 25-34 years:

• CIN is the most common pathology underlying AGC in this age group. 1
• Endometrial sampling is not routinely required unless unexplained vaginal bleeding or endometrial cancer risk factors are present. 1

For women aged ≥35 years:

• Endometrial sampling is mandatory as part of the initial evaluation. 1, 2
• The risk of both cervical and endometrial pathology increases with age. 1

Long-Term Surveillance

After treatment or negative initial evaluation:

• Surveillance should continue for at least 25 years after treatment for high-grade precancer. 6, 7
• Initial post-treatment testing includes HPV test or cotest at 6,18, and 30 months. 6, 7
• Do not return to routine screening intervals until adequate negative follow-up is documented. 5