Prediction of Survival and Disease Control in HPV-Negative Head and Neck Cancer Using Molecular Markers

Key Points

  • Researchers were able to identify five miRNAs—hsa-let-7g-3p, hsa-miR-6508-5p, hsa-miR-210-5p, hsa-miR-4306 and hsa-miR-7161-3p—whose expression predicted the course of the disease and the risk of recurrence.
  • The signature also predicted overall, recurrence-free, and disease-specific survival.

A new method may predict the course of human papillomavirus (HPV)-negative head and neck cancer after radiochemotherapy. According to findings published by Hess et al in Clinical Cancer Research, five microRNAs (miRNAs) may be able to provide the decisive data.

Squamous cell carcinomas of the head and neck (HNSCC) are often diagnosed at an advanced stage and may have a relatively poor prognosis. Increased risk factors for HNSCC include HPV, tobacco smoking, and alcohol consumption.

“While the virally-induced tumors can be treated relatively well, the other head and neck tumors have a rather poor prognosis,” said Claus Belka, MD, head of the Clinical Cooperation Group (CCG) Personalized Radiotherapy in Head and Neck Cancer. “In this study, we investigated how molecular markers can be used to define subgroups that undergo a different course of disease after radiation chemotherapy,” Dr. Belka said. This could offer an opportunity for personalized treatment.”

miRNAs are a class of molecules consisting of short sequences of RNA building blocks. Unlike protein synthesis, however, RNA is not needed for the construction of molecules. On the contrary, many miRNAs are able to prevent the build-up of certain proteins by degrading the corresponding RNA blueprint. It is estimated that currently about 2,000 different miRNAs are known.

In 2016, the scientists had already identified a miRNA signature that makes it easier to estimate the course of the disease in brain tumors.

Findings

Researchers examined cancer tissues from two independent tissue sample collections: a multicenter patient collective and a monocentric patient collective. In the analysis, the researchers focused on miRNAs, tiny molecules that influence the expression of numerous (in part cancer-relevant) genes. “Working with our colleagues enabled us to study a total of 162 samples from patients with HPV-negative head and neck cancer,” said the authors.

Out of all of the miRNAs, the researchers were able to identify five miRNAs—hsa-let-7g-3p, hsa-miR-6508-5p, hsa-miR-210-5p, hsa-miR-4306 and hsa-miR-7161-3p—whose expression predicted the course of the disease and the risk of recurrence. The signature also predicted overall survival (hazard ratio [HR] = 3.03, 95% confidence interval [CI] = 1.50−6.12, P = .001), recurrence-free survival (HR = 3.16, 95% CI = 1.65−6.04, P < .001), and disease-specific survival (HR = 5.12, 95% CI = 1.88−13.92, P < .001).

“In combination with other clinical data, this five miRNA signature allows the definition of four groups with different prognoses,” said authors.

“Such molecular markers are the first prerequisite for personalized treatment approaches in HPV-negative head and neck tumors,” said Dr. Belka. "If these figures can be confirmed on a large scale, personalized adjustments in therapy intensity could be derived from them in the future.” For example, it would be conceivable to reduce the intensity of therapy in patients with a low risk of recurrence, or to increase it in high-risk patients. In addition, it is now possible to search for the genes that are influenced by the five miRNAs and find out whether they represent worthwhile target structures for therapy. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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