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The aim of this study is to incorporate polarized hyperspectral imaging (PHSI) with machine learning for automatic detection of head and neck squamous cell carcinoma (SCC) on hematoxylin and eosin (HE) stained tissue slides. A polarized hyperspectral imaging microscope had been developed in our group. In this paper, we imaged 20 HE stained tissue slides from 10 patients with SCC of the larynx by the PHSI microscope. Several machine learning algorithms, including support vector machine (SVM), random forest, Gaussian naive Bayes,