Objective: To evaluate the diagnostic performance of fluorine 18 fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (¹⁸F-FDG PET/MR) in the preoperative staging of hypopharyngeal cancer (HPC), compare it with conventional enhanced computed tomography (CT) and MR, and further explore the prognostic value of its metabolic and diffusion metrics for HPC. Methods: This retrospective study included 33 patients with pathologically confirmed HPC. All patients underwent preoperative ¹⁸F-FDG PET/MR, CT, and MR examination. The staging performance of the three modalities was evaluated using pathological staging as a reference. Additionally, metabolic indicators and diffusion-related parameters from PET/MR were collected to investigate their impact on larynx preservation and survival. Results: PET/MR demonstrated accuracies of 90.9% and 71.4% in the preoperative T and N staging, respectively, significantly higher than those of CT (54.5%, p = 0.001; 42.9%, p = 0.021) and MR (66.7%, p = 0.016; 42.9%, p = 0.021). On the whole, significant differences emerged in the maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), minimum apparent diffusion coefficient (ADCmin), and mean ADC (ADCmean) and combined ratios across different T stages, while SUVmax, mean SUV (SUVmean), total lesion glycolysis (TLG), and MTV varied significantly across different N stages. The ADCmin and ADCmean showed good predictive capability for larynx preservation, with AUCs of 0.857 and 0.920 (p < 0.05), respectively. In Cox multivariate analysis of overall survival, high-level ADCmean (p = 0.004) and low-level TLG/ADCmean (p = 0.022) were significantly associated with better survival. Conclusion: In HPC, ¹⁸F-FDG PET/MR imaging significantly surpasses CT and MR in preoperative diagnostic staging. Its diffusion-related parameters have substantial prognostic value, with high ADC values associated with larynx preservation. ADCmean and TLG/ADCmean are potential prognostic indicators for HPC.

Head and neck squamous cell carcinoma (HNSCC) is characterized by frequent recurrence and poor survival, highlighting the need for reliable biomarkers for risk stratification and therapeutic guidance. Folate-mediated one-carbon metabolism has been linked to tumor development; however, its prognostic and immunological relevance in HNSCC remains unclear. Using The Cancer Genome Atlas (TCGA) transcriptomic data, we developed and validated a folate metabolism–related gene signature (FMRG_score). An 11-gene model constructed by least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression effectively stratified patients into distinct survival groups and served as an independent prognostic factor. A nomogram integrating FMRG_score with clinical variables demonstrated favorable predictive performance. Functional enrichment analyses revealed activation of oncogenic pathways in high-risk tumors. Immune deconvolution indicated that elevated FMRG_score was associated with reduced anti-tumor immune infiltration, increased macrophage-related signals, and an immunosuppressive tumor microenvironment. Drug response prediction suggested higher estimated IC ₅₀ values in the high-risk group, showing potential chemoresistance. Mechanistically, CYP27B1 knockdown suppressed malignant phenotypes and enhanced cisplatin sensitivity. Collectively, these findings establish folate metabolism as a metabolic–immune axis in HNSCC and suggest that the FMRG_score may serve as a prognostic and therapeutic stratification tool.