Researchers at the University of Michigan have identified a new metric that they say determines the relationship between nerve density and oral cancer.
The team led by Dr. Nisha D'Silva, Ph.D., reported that tumors with high normal nerve density (NND), or a change in the distribution of nerves in the oral cavity, are associated with poor survival in patients with tongue cancer. They also noted that patients with high levels of NND and shorter nerve-tumor distance had worse outcomes.
Perineural invasion in oral squamous cell carcinoma is associated with poor survival. The researchers also noted that due to the risk of recurrence, patients often receive additional therapy after surgery. Previous studies have already shown that nerves in the tumor microenvironment promote aggressive tumor growth.
The researchers wanted to study NND further to translate previous mechanistic studies into a context that could be used in practice. They examined how the density of nerves within a tumor relates to its growth.
The team created a standardized nerve density metric to account for differences in how nerves are distributed in the oral cavity. They called this metric the normal density curve. Metric also used nearby tissue to compare and determine normal density for different areas of the mouth.
The researchers reported that disease-specific survival decreased as intratumoral nerve density increased and nerve density normalized in tongue cancer. They also showed an association between NND and the unfavorable pattern of perineural invasion.
The team also reported that dorsal root ganglion increased tumor size, while denervation decreased tumor growth. Finally, the research team reported that the automatic nerve detection technology and manual nerve detection showed high agreement, with an F1 score of 0.977. The team hypothesized that if they could identify which cancers would act more aggressively from the start, they could then be treated with the same urgency.