What is the likelihood of adenocarcinoma with High-grade Squamous Intraepithelial Lesions (HSIL) and Atypical Glandular Cells (AGC)?

Risk of Adenocarcinoma with HSIL and AGC

The combined presence of High-grade Squamous Intraepithelial Lesions (HSIL) and Atypical Glandular Cells (AGC) on cervical cytology indicates a very high risk of underlying adenocarcinoma or significant cervical disease, with HPV-positive AGC carrying a 45% risk of histologic HSIL and cancer. 1, 2

Risk Assessment by Cytologic Finding

• HSIL alone carries a 69% risk of histologic HSIL and cancer, requiring immediate colposcopy 1
• AGC alone carries a 13% risk of histologic HSIL and cancer, also requiring immediate colposcopy 1
• When HPV testing is positive with AGC, the risk increases to 45% for histologic HSIL and cancer 1
• Even HPV-negative AGC carries a 2.2% risk of histologic HSIL and cancer, still warranting immediate colposcopy 1
• The combination of HSIL and AGC represents a particularly concerning finding with increased risk of both squamous and glandular lesions, including adenocarcinoma 2

Adenocarcinoma Risk with Combined Findings

• Research shows that abnormal glandular cells can coexist with HSIL in approximately 28% of cases, and invasive carcinoma (including adenocarcinoma) in 38.7% of cases 3
• Long-term follow-up studies of patients with AGC reveal that 40.1% have clinically significant lesions, including endocervical adenocarcinoma in situ (AIS) and endocervical or endometrial adenocarcinoma 4
• Adenocarcinoma in situ (AIS), a precursor to invasive adenocarcinoma, can be detected through abnormal cytology that initially presents as either squamous abnormalities (57.3%) or glandular abnormalities (37.3%) 3
• The presence of both HSIL and AGC significantly increases the likelihood of underlying adenocarcinoma compared to either finding alone 2, 3

Management Recommendations

• Immediate colposcopy with endocervical sampling is mandatory for patients with HSIL and AGC 1, 2
• HPV DNA testing should be performed as part of the initial evaluation 2
• Endometrial sampling is recommended for women 35 years and older or younger women with risk factors for endometrial cancer 2
• Diagnostic excisional procedure (LEEP or cold knife conization) is strongly recommended when both HSIL and AGC are present, as colposcopy alone may miss significant disease 2, 5
• Reflex HPV testing or repeat cytology alone is unacceptable as initial management 2

Pitfalls to Avoid

• Do not underestimate the significance of combined HSIL and AGC findings - even with negative HPV testing, the risk of significant disease remains high 2, 5
• Colposcopy can miss a significant number of lesions, particularly adenocarcinoma and its precursors, which can lead to serious consequences if not detected 5, 3
• Do not rely solely on HPV testing or repeat cytology for initial management 2
• Diagnostic cone excision is essential if AIS lesion is noted in cervical biopsy specimen since nearly 40% have coexisting invasive lesions 3
• Long-term follow-up is critical as some clinically significant lesions may be diagnosed after a mean of 37 months despite initial negative findings 4

Special Populations

• For pregnant women with HSIL and AGC, colposcopy is recommended but treatment is generally deferred until after delivery unless invasive cancer is detected 1, 5
• Endocervical curettage is unacceptable in pregnant women 1, 5
• Careful follow-up is essential for HIV-infected women as the risk for recurrence of squamous intraepithelial lesions and cervical cancer after conventional therapy is increased 5