Fused Raman spectroscopic analysis of blood and saliva delivers high accuracy for head and neck cancer diagnostics

As a rapid, label-free, non-destructive analytical measurement requiring little to no sample preparation, Raman spectroscopy shows great promise for liquid biopsy cancer detection and diagnosis. We carried out Raman analysis and mass spectrometry of plasma and saliva from more than 50 subjects in a cohort of head and neck cancer patients and benign controls (e.g., patients with benign oral masses). Unsupervised data models were built to assess diagnostic performance. Raman spectra collected from either biofluid provided moderate performance to discriminate cancer samples. However, by fusing together the Raman spectra of plasma and saliva for each patient, subsequent analytical models delivered an impressive sensitivity, specificity, and accuracy of 96.3%, 85.7%, and 91.7%, respectively. We further confirmed that the metabolites driving the differences in Raman spectra for our models are among the same ones that drive mass spectrometry models, unifying the two techniques and validating the underlying ability of Raman to assess metabolite composition. This study bolsters the relevance of Raman to provide additive value by probing the unique chemical compositions across biofluid sources. Ultimately, we show that a simple data augmentation routine of fusing plasma and saliva spectra provided significantly higher clinical value than either biofluid alone, pushing forward the potential of clinical translation of Raman spectroscopy for liquid biopsy cancer diagnostics.