Abstract
The potential relationship between fungal biology and cervical cancer remains poorly understood. This study aimed to assess the ability of ChatGPT-4o to generate research hypotheses concerning possible links between fungal factors, HPV persistence, and cervical carcinogenesis. ChatGPT-4o generated hypotheses in three prespecified domains: microbial dysbiosis, inflammation, and immune modulation. Three author-evaluators with expertise in pathology, oncology, and microbiology independently assigned overall evaluation scores and assessed the scientific reasonableness of experimental-plan components. Targeted literature searches identified publications directly addressing each proposed mechanism. Inter-rater reliability was quantified using a two-way random-effects, absolute-agreement intraclass correlation coefficient (ICC) and pairwise quadratic-weighted Cohen's kappa. No human-generated hypothesis set, alternative language model, or repeated independent AI session was included. ChatGPT-4o generated 55 hypotheses. No directly matching publication was identified for 48 hypotheses under the prespecified search framework; this finding was interpreted as indicating an underexplored direction, not proof of novelty. Based on the predefined composite evaluation rubric, 35 hypotheses (63.6%) received high mean evaluation scores and 20 (36.4%) received moderate mean evaluation scores. Agreement for hypothesis scores was high (ICC (2,1) = 0.975; pairwise weighted kappa = 0.963-1.000). Among 18 experimental-plan components, 12 received high mean scores and 6 received moderate mean scores; agreement was lower but still strong (ICC (2,1) = 0.821; weighted kappa = 0.727-0.914). Representative hypotheses concerned fungal metabolites and oxidative stress, fungal-associated inflammation and oxidative damage, and fungal modulation of immune-checkpoint pathways. This pilot study suggests that ChatGPT-4o can generate diverse and potentially testable hypotheses concerning fungal biology and cervical cancer. However, the generated hypotheses should be regarded as exploratory research directions rather than validated mechanisms and require independent literature verification and experimental validation.