Spatial transcriptomic analysis of head and neck squamous cell carcinoma reveals novel regulators of hybrid epithelial-to-mesenchymal transition

Here we use spatial transcriptomics (ST) to profile both HPV-positive and HPV-negative HNSCC, uncovering distinct patterns of spatial organization of malignant cells and the surrounding tumor microenvironment across groups of tumors. First, we find that HPV-positive HNSCC is characterized by high cellular density in all cellular compartments with distinct expression of hypoxia, senescence, and cell cycle-associated genes in the malignant compartment.

In HPV-negative HNSCC, we find two distinct spatial patterns of a partial epithelial-to-mesenchymal transition (p-EMT) program. One pattern is spatially associated with fibroblasts, characterized by p-EMT at the leading edge of tumor nests (“p-EMT edge”), and mediated by TGFB-signaling. The other pattern features high p-EMT expression in the core of tumor nests (“p-EMT core”).