NYU study shows oral cancer pain may predict likelihood of cancer spreading

An oral cancer patient's pain intensity score could predict cancer metastasis, helping with future testing options and surgical decision-making, according to a study from the New York University College of Dentistry.

The authors of "Oncogenes Overexpressed in Metastatic Oral Cancers from Patients with Pain: Potential Pain Mediators Released in Exosomes," published in September by Scientific Reports, an open-access journal from Nature Research, used a questionnaire to document the pain experienced by 72 oral cancer patients before oral cancer surgery. While most patients reported some pain, those with the most pain were more likely to have cancer that had spread to lymph nodes in the neck, suggesting patients with less pain were at lower risk of metastasis, according to the study.
"While we need to undertake a follow-up study, our current data reveal that a patient's pain intensity score works as well as the current method — depth of invasion, or how deeply a tumor has invaded nearby tissue — as an index to predict metastasis," lead author Aditi Bhattacharya, Ph.D., said in an NYU news release about the study.

To help understand why metastatic cancers are more painful, the researchers looked for differences in gene expression in metastatic cancers from patients with high levels of pain and nonmetastatic cancers from patients not experiencing pain and identified 40 genes that were more highly expressed in painful metastatic cancers, suggesting those genes are associated with oral cancer metastasis and mediate cancer pain, according to the study.

One cause of cancer pain is attributable to the release of mediators from cancers that sensitize nerves near the tumor. Many of the 40 genes identified in this study code for proteins found in exosomes, small vesicles that break away from a cell and can be taken up by other cells. This is a potential mechanism for how oral cancer cells affect nerves, according to the study.

When the researchers injected the paws of mice with the extracellular fluid of oral cancer cells grown in culture, only those animals injected with the fluid containing exosomes experienced pain. This suggests exosomes from cancer may be responsible for oral cancer pain, according to the study.

"The identified genes are targets for therapy aimed at stopping pain and cancer. In addition, exosomes shed from cancers can be detected in saliva, blood and urine, offering the potential for an objective molecular test to diagnose risk of metastasis," said Donna Albertson, Ph.D., professor in the department of oral and maxillofacial surgery at the NYU College of Dentistry, an investigator at the NYU Bluestone Center for Clinical Research and the study's corresponding author.

When oral cancer spreads to lymph nodes in the neck, a patient's chance of survival is cut by half, according to the release. Because it's often unclear through imaging and physical assessment if oral cancer has spread, most oral cancer surgeries include preemptively removing lymph nodes, even though research shows as many as 70% of these prophylactic neck dissections are unnecessary, the release stated.

"Clinicians and researchers are keen to define a biomarker that accurately predicts metastasis," said Dr. Bhattacharya, who is also an assistant professor in the department of oral and maxillofacial surgery at the NYU College of Dentistry and an investigator at the NYU Bluestone Center for Clinical Research. "Given that patients with metastatic oral cancer experience more pain, we thought that a patient’s level of pain might help predict metastasis. A surgeon could then use this knowledge to only remove lymph nodes in patients with cancers that are most likely to metastasize."

The study was supported by grants from the National Institutes of Health.