Safety-Oriented Benchmarking of Large Language Models in Risk-Based Management of Abnormal Cervical Screening...

Large language models (LLMs) are increasingly being considered for clinical decision support, yet their safety in risk-based cervical screening management remains insufficiently characterized.

This study benchmarked the guideline concordance and safety-related performance of 3 LLMs in the initial American Society for Colposcopy and Cervical Pathology (ASCCP) risk-based management of abnormal cervical screening results, using a purposively constructed synthetic scenario set that oversamples complex and history-dependent decision nodes.

We developed 60 synthetic clinical scenarios reflecting initial abnormal screening management in immunocompetent, nonpregnant women aged 25 to 65 years using a predefined scenario coverage matrix. GPT-5.3, Gemini 3 Flash, and DeepSeek V3.2 were tested under 2 prompt conditions: Baseline Clinical Prompt and Guideline-Directed Prompt Package. Each scenario was run in 3 independent repetitions per model and prompt arm (1080 total observations). Responses were evaluated by 2 obstetrics and gynecology specialists, blinded to model and prompt-arm identity but not independent of gold-standard construction, using a prespecified rubric. The primary end point was the unsafe major error-free rate. Proportions are reported with CIs adjusted for within-scenario clustering, and generalized estimating equations were used for inferential comparisons.

Under the guideline-directed prompt package, the unsafe major error-free rate was 100% (95% CI 94%-100%) for GPT-5.3, 98.9% (95% CI 94%-99.8%) for Gemini 3 Flash, and 75% (95% CI 63.2%-84%) for DeepSeek V3.2. In the main-effects model, the guideline-directed prompt package was associated with higher odds of both unsafe major error-free performance (odds ratio [OR] 3.76, 95% CI 2.45-5.77; P<.001) and exact concordance (OR 8.27, 95% CI 4.14-16.52; P<.001). Error rates increased substantially with scenario complexity, rising from 3.1% in low-complexity to 29% in high-complexity scenarios. The most frequent error subtypes were undermanagement, genotype misinterpretation, and history neglect. Interrater agreement was almost perfect (weighted κ=0.839, 95% CI 0.811-0.867).

Safety-oriented benchmark performance in initial ASCCP risk-based management varied markedly by model, prompt condition, and scenario complexity. The guideline-directed prompt package was associated with improvement in both safety and guideline concordance, but even the best-performing model remained vulnerable in complex, history-dependent scenarios. LLMs may have value as clinician-supervised decision support tools, but these benchmark findings should not be interpreted as supporting autonomous clinical use in cervical screening management.