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American researchers have identified two new human papillomavirus subtypes involved in the development of certain head and neck cancers, called head and neck squamous cell carcinomas (HNSCC). This discovery could help in the development of personalized treatments for patients affected by this type of cancer.
Cases of head and neck cancer associated with human papillomaviruses (HPV) are on the rise in the United States. But little is known about the risk factors for these cancers and the mechanisms involved in the fact that some tumors are more aggressive and more resistant to treatment than others. American researchers wanted to understand why some patients responded better to radiotherapy treatment than others.
Understand why not all tumors respond the same way to treatment
Their work, published in the journal Proceedings of the National Academy of Sciences, revealed that the HPVs responsible for head and neck cancers can be divided into two distinct subtypes that will be decisive in the response to treatment. Indeed, one of the subtypes identified would be more receptive to treatment than the other. The researchers also brought to light an unprecedented mechanism of carcinogenesis associated with HPV (when the papillomavirus transforms into cancer).
Patients with squamous cell carcinoma of the head and neck associated with an HPV virus are now treated with radiotherapy combined with chemotherapy. But these treatments can lead to lifelong adverse effects (difficulty swallowing, muscle fibrosis, hardening of the arteries, etc.). Personalized therapy could help oncologists choose the best treatment(s) for each patient. However, it is difficult for doctors to determine the type and intensity of treatment for each patient without knowing how the tumor will respond to treatment. This is precisely what the researchers worked on.
High-expressing tumors and low-expressing tumors
After analyzing tumor samples, they were able to identify several groups of co-expressed genes (when several genes are expressed under similar conditions). One of these co-expressed genes made it possible to separate the tumors into two groups: high-expression tumors and low-expression tumors. Tumors with a high NF-kB transcription factor were associated with a better prognosis than tumors with a low NF-kB transcription factor.
The main distinction between the two tumor types is the survival prognosis, according to the researchers. To better understand why one HPV subtype is less dangerous than the other, the researchers reproduced cellular models of each subtype in the laboratory. “Tumors with a high NF-kB transcription factor responded better to radiotherapy, suggesting that patients with these tumors are more likely to survive.” said Wendell Yarbrough, co-author of the study. “We know that something is going on that allows the activation of the transcription factor NF-kB to make tumors more sensitive to treatment with radiotherapy, which could explain why some patients recover better from this type of cancer than others.”he added.
This work could be used to identify the patients who will have the best chance of surviving and to develop new personalized treatments that are more effective and have fewer side effects.