RTP On Demand — Head & Neck/Thyroid | Research To PracticeMolecular phenotypes of squamous cell cancer of the head and neck
3:48 minutes.
TRANSCRIPTION:
DR COHEN: We now have the publication of the molecular phenotype of squamous cell carcinoma of the head and neck. And this was, of course, the TCGA effort. It’s important in many respects, as it is with other cancers. It really begins to give us a framework of how to view these cancers molecularly. So the first important point to make is that HPV-positive and HPV-negative disease are completely different entities, biologically. We’ve known that they’re different clinically, and now we realize that the clinical differences really are a product of dramatic molecular differences. HPV-negative disease, in general, is driven by tumor suppressors, p53, p16, FAT1. And HPV-positive disease is not only inactivation of p53 and RB by the virus but also driven by oncogenes, such a PIK3CA, very high rate of PI3 kinase pathway alterations in HPV-positive disease. So that’s the first thing. The second is that we can begin to divide these cancers into different pathways, such as the EGFR pathway, such as an immune pathway or the differentiation pathway that involves NOTCH1. And it’s important to do that, because we can begin to develop different therapeutics for these different patients. And then along those lines, we begin to realize that the immune alterations in many of these cancers can be dramatic, especially in HPV-positive disease, where a quarter of patients with HPV-positive cancers — and a substantial number in HPV-negative — have alterations in immune signaling that essentially make these cancers unrecognizable to the immune system. And these are patients who likely need different therapies than, let’s say, checkpoint inhibitors. They need therapies that will help the immune system actually recognize the cancers. So I think these are incredible data sets. There’s much more to learn, much more to begin to mine from the data, but initially we have some very interesting and very important points to make about the biology of head and neck cancer. DR LOVE: Oncologists are hearing more and more about intrinsic subtypes, certainly you heard that for a long time in breast cancer, starting to hear it in other tumors, although sometimes I wonder exactly what it means clinically. Are we starting to come out with intrinsic subtypes of head and neck cancer? DR COHEN: We are. It’s clear now that, just as in other diseases and most notably in breast cancer, where this has been well developed, that there probably are 5 different subtypes of head and neck cancer: 3 HPV-negatives, 2 HPV-positives. And they appear to signal differently. They have different genes in their expression portfolios. And they appear to do differently. Their outcomes are different. Even in the context of HPV-positive, the subsets do differently. So I do believe that it is important and, as we get more sophisticated in terms of these types of analyses and more sophisticated in terms of the therapeutics that we can apply, I’m fairly confident that we’ll be treating these patients quite differently in the near future. |