Risk-Based Triage Using Cytology and HPV Genotyping to Reduce Unnecessary Colposcopy: A Real-World Cross-Sectional Study

Background and Objectives: Despite the widespread adoption of HPV-based cervical cancer screening, the optimal triage strategy for women with low-grade cytological abnormalities and non-16/18 high-risk HPV (hrHPV) types remains debated. This study evaluated the impact of ASCCP risk-based triage strategies on colposcopy referral and biopsy outcomes in a large tertiary care center. Methods: This retrospective cross-sectional study included 2748 sexually active women aged 30–65 years who underwent colposcopy at Ankara Etlik City Hospital (January 2023–June 2025). Of these, 1932 met ASCCP criteria for cervical biopsy. Cytology results, HPV genotypes (16, 18, and other hrHPV types), and histopathological findings were analyzed. CIN3+ (CIN3, adenocarcinoma in situ, or invasive carcinoma) was the primary outcome. Multivariable logistic regression identified independent predictors, with model fit assessed by Nagelkerke R2 and the Hosmer–Lemeshow test. Results: The mean age was 42.8 ± 8.1 years. The overall CIN3+ prevalence was 15.9% (308/1932). HSIL cytology was the strongest independent predictor of CIN3+ (adjusted OR 22.41, 95% CI: 11.28–44.52). HPV16/18 combined with HSIL or ASC-H cytology conferred the highest risk (adjusted OR 17.88–21.67). Women with ASC-US or LSIL cytology and non-16/18 hrHPV types had CIN3+ rates below 10%. Irregular screening history was also an independent predictor (adjusted OR 1.38). A risk-based triage approach suggested a potential reduction of approximately 29.7% in colposcopy utilization. However, this estimate applies exclusively to the biopsied subgroup and does not account for potentially undetected lesions in the 816 non-biopsied women enrolled in surveillance follow-up. Conclusions: HSIL cytology and HPV16/18 positivity represent the highest-risk profile for CIN3+ and should remain primary indications for colposcopy. Conversely, women with ASC-US or LSIL cytology and non-16/18 hrHPV types may be candidates for surveillance-based co-testing rather than immediate colposcopy, potentially enabling a resource-efficient reduction in unnecessary procedures within the biopsied cohort studied. Prospective validation in broader colposcopy-referred populations is needed before generalizing these findings to primary screening settings.