US researchers have identified a new metric to articulate the relationship between nerve density and oral cancer. The study—by researchers at the University of Michigan Rogel Cancer Center and the School of Dentistry, and published in Clinical Cancer Research—investigated normalised nerve density to translate previous mechanistic studies into a context that could be used in the clinic.
“We are recognising more and more that there’s a very dynamic interaction between nerves and cancer cells in the tumour microenvironment,” senior author Dr Nisha D’Silva said.
The team looked at how the density of nerves within a tumour tied with the tumour’s growth. The oral cavity has several regions, each with different functions. The way each area receives nerves is distinct; the nerves in the inside of the cheek have a different role and are fewer than nerves on the tongue. Given these variations, looking at nerve density of the tumour without considering the normal innervation of the different areas in the oral cavity and each individual’s variation to assess whether a tumour is aggressive leaves an inaccurate picture.
To account for this, the team created a standardised metric for nerve density to clarify the variation in distribution of nerves in the oral cavity, called normalised nerve density, and showed its importance in tumour progression. Most of the work was done with human tissue, and the team then validated the findings using a mouse model.
They used adjacent tissue to compare and determine a ‘normalised’ density for different regions in the oral cavity.
“We showed that tumours with high normalised nerve density seem to be associated with poor survival for patients with tongue cancer, which is the most common type of oral cancer,” Dr D’Silva said.
“We also found that patients with high normalised nerve density and a smaller distance between the nerve and the tumour have poorer outcomes.”
Additionally, the team explored the use of artificial intelligence to measure normalised nerve density, which could facilitate the use of this metric in clinical practice.
A challenge with treating oral cavity cancers is their tendency to recur.
“The question becomes, how can you look for factors that could contribute to progression? How can you use nerve features to figure out which cancers will behave more aggressively?” Dr D’Silva said.
He added that if researchers can figure out which cancers are likely to behave more aggressively from the outset, then they can treat the tumours more aggressively from the beginning. Normalised nerve density provides researchers with another data point to determine the best course of treatment.
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