Clinical Significance of Atypical Squamous Cells of Undetermined Significance (ASC-US) and Atypical Squamous Cells-Cannot Exclude High-Grade Squamous Intraepithelial Lesion (ASC-H) in a Low-Income Clinical Setting: A Retrospective Analysis

Background: Atypical squamous cells represent a significant category in cervical cytology screening, with a varying degree of malignant potential between ASC-US and ASC-H. In low-resource settings, challenges in follow-up and testing necessitate a clear understanding of the risk associated with these diagnoses. Objective: To determine the Positive Predictive Value (PPV) for premalignant and malignant cervical lesions (CIN2+) in patients with ASC cytology results, and to evaluate management challenges, particularly the high loss to follow-up, in a low-resource clinical setting. Methods: This retrospective study analyzed 276 patients with ASC cytology results from February 2019 to December 2024 at a tertiary care center. Patients were categorized into ASC-US (n=210) and ASC-H (n=66) groups. Demographics, histological outcomes, HPV testing results, and management patterns were analyzed. Statistical analysis was performed using Pearson’s Chi-Square and Fisher’s Exact Tests. The primary outcome was the PPV for CIN2+ among the 85 (30.8%) patients who underwent histological verification. Results: Among 1,360 cervical cytology specimens, ASC prevalence was 20.3% (ASC-US: 15.4%, ASC-H: 4.8%). Biopsy was performed in 30.8% of patients (n=85). The Positive Predictive Value (PPV) for CIN2+ was significantly higher for ASC-H compared to ASC-US (ASC-H: 40% [16/40] vs. ASC-US: 4.4% [2/45]; p<0.001). One case of endometrial carcinoma was identified in the ASC-H group but was excluded from the PPV calculation for cervical CIN2+ lesions. HPV testing was performed in only 13.8% of cases, with a 68.4% positivity rate, reflecting significant selection bias. Loss to follow-up (LTFU), defined as no follow-up within 12 months, occurred in 75.7% of all cases. Conclusions: ASC-H carries a substantially higher risk for significant cervical pathology compared to ASC-US, supporting differential management approaches. The extremely high rate of loss to follow-up (75.7%), strictly defined as no record of colposcopy, biopsy, or repeat cytology within 12 months of the index ASC finding,  is a critical programmatic failure that severely limits the generalizability of these findings and underscores the urgent need for systematic patient tracking, enhanced patient education, and the integration of costeffective screening technologies like self-collection HPV testing to improve patient outcomes in low-resource settings.