ATR-FTIR Spectroscopy with Chemometrics for Analysis of Saliva Samples Obtained in a Lung-Cancer-Screening Programme: Application of Swabs as a Paradigm for High Throughput in a Clinical Setting.

There is an increasing need for inexpensive and rapid screening tests in point-of-care clinical oncology settings. Herein, we develop a swab "dip" test in saliva obtained from consenting patients participating in a lung-cancer-screening programme being undertaken in North West England. In a pilot study, a total of 211 saliva samples ( = 170 benign, 41 designated cancer-positive) were randomly taken during the course of this prospective lung-cancer-screening programme. The samples (sterile Copan blue rayon swabs dipped in saliva) were analysed using attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy. An exploratory analysis using principal component analysis (PCA,) with or without linear discriminant analysis (LDA), was then undertaken. Three pairwise comparisons were undertaken including: (1) benign vs. cancer following swab analysis; (2) benign vs. cancer following swab analysis with the subtraction of dry swab spectra; and (3) benign vs. cancer following swab analysis with the subtraction of wet swab spectra. Consistent and remarkably similar patterns of clustering for the benign control vs. cancer categories, irrespective of whether the swab plus saliva sample was analysed or whether there was a subtraction of wet or dry swab spectra, was observed. In each case, MANOVA demonstrated that this segregation of categories is highly significant. A k-NN (using three nearest neighbours) machine-learning algorithm also showed that the specificity (90%) and sensitivity (75%) are consistent for each pairwise comparison. In detailed analyses, the swab as a substrate did not alter the level of spectral discrimination between benign control vs. cancer saliva samples. These results demonstrate a novel swab "dip" test using saliva as a biofluid that is highly applicable to be rolled out into a larger lung-cancer-screening programme.