New clue hints at how head and neck cancers spread

Researchers have discovered that aggressive cancer cells can appear in distinct locations within head and neck tumors, offering new insights into why some cancers—especially squamous cell carcinomas not caused by HPV—are harder to treat. The findings, published in Nature Genetics, reveal two unique spatial patterns where these aggressive cells can be found.

One known location is at the tumor's outer edge, where cells start invading surrounding tissue. The other, newly identified location is deep within the tumor's core. Professor Sidharth Puram, from WashU Medicine’s otolaryngology—head and neck surgery department, emphasizes the significance of understanding the tumor's complex ecosystem using spatial approaches.

These aggressive cells, known as partial epithelial-to-mesenchymal transition (EMT), were found in different areas, challenging previous views on head and neck tumor behavior. The study analyzed tumors from HPV-positive and HPV-negative patients with head and neck squamous cell carcinoma. By mapping the locations of these cells, researchers found that aggressive cells in the core appeared after interacting with immune cells, particularly macrophages that release a protein called Oncostatin M (OSM).

This signal triggers the cells' more aggressive behavior. Puram notes that different treatment strategies may be necessary for tumors with aggressive cells at the edge versus those in the core, as distinct triggers are involved. While most aggressive cells were found at the tumor's edge, up to one-third of HPV-negative cancers exhibited the core pattern.

Puram stresses that understanding how these cell locations affect treatment responses and patient outcomes is crucial. Further research aims to block the signals that make these cells aggressive, potentially leading to new treatment options for head and neck cancers, which are the sixth most common globally.