The findings were further supported by immune infiltration analyses, molecular docking and molecular dynamics simulations and validation using clinical HNSC specimens, including single-cell RNA sequencing of collected samples, scTenifoldKnk virtual knockout modeling and immunofluorescence staining/histological assessment of HNSC tissues.<h4>Results</h4>Among 4907 plasma proteins, MR identified prefoldin subunit 2 (PFDN2) as a protective factor against hypopharyngeal carcinoma, with no evidence of reverse causality. This evidence concerns the gene PFDN2 and hypopharyngeal carcinoma.