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Objectives  Intraductal papillary mucinous neoplasms (IPMNs) are cystic precursor lesions to pancreatic cancer. The presence of oral microbes in pancreatic tissue or cyst fluid has been associated with high-grade dysplasia (HGD) and cancer. The present study aims at investigating if humoral immunity to pancreas-associated oral microbes reflects IPMN severity.    Design  Paired plasma ( n  = 109) and saliva ( n  = 65) samples were obtained from IPMN pancreatic cystic tumor cases and controls, for anti-bacterial antibody analysis and DNA quantification by enzyme-linked immunosorbent assay (ELISA) and qPCR, respectively. Tumor severity was graded by histopathology, laboratory, and clinical data. Circulating plasma and salivary antibody reactivity to a pancreas-associated oral microbe panel were measured by ELISA and correlated to tumor severity.    Results  The patient group with high-risk cystic tumors (HGD and/or associated invasive cancer) shows ample circulating IgG reactivity to  Fusobacterium nucleatum  ( F. nucleatum ) but not to  Granulicatella adiacens  ( G. adiacens ), which is independent of the salivary bacteria DNA levels. This group also shows higher salivary IgA reactivity to  F. nucleatum , Fap2 of  F. nucleatum , and  Streptococcus gordonii  ( S. gordonii ) compared to low-risk IPMN and controls. The salivary antibody reactivity to  F. nucleatum  and Fap2 are found to be highly correlated, and cross-competition assays further confirm that these antibodies appear cross-reactive.    Conclusion  Our findings indicate that humoral reactivity against pancreas-associated oral microbes may reflect IPMN severity. These findings are beneficial for biomarker development.

Circulating and Salivary Antibodies to Fusobacterium nucleatum Are Associated With Cystic Pancreatic Neoplasm Malignancy