Yeah, it’s a really exciting finding that there’s two subtypes of HPV-associated cancers. And our group discovered these through an unsupervised analysis of gene set expressions, so co-expressed genes. And of the more than 20 sets of genes, we identified only one set that separated patient’s tumors into those with high or low expression naturally. So this unsupervised clustering identified two sets of tumors, and the distinguishing characteristic of that gene set was NF-kappa B signaling...
Yeah, it’s a really exciting finding that there’s two subtypes of HPV-associated cancers. And our group discovered these through an unsupervised analysis of gene set expressions, so co-expressed genes. And of the more than 20 sets of genes, we identified only one set that separated patient’s tumors into those with high or low expression naturally. So this unsupervised clustering identified two sets of tumors, and the distinguishing characteristic of that gene set was NF-kappa B signaling. So we went on to now analyze eight cohorts of patients from Europe and the United States and using different tumor collections and processing at the local hospitals. Some of the data was analyzed by RNA-Seq and some was analyzed by NanoString and some was analyzed by Affymetrix. So regardless of how the tumors were analyzed or where they were from, the two subtypes could be identified in these cohorts. And out of the eight cohorts and 975 patients, the hazard ratio was 3.5 for the poor prognosis subgroup compared to the good prognosis subtype. So basically, what we’re saying is there’s a robust marker to identify two subtypes of head and neck cancer, one that’s in a low-risk subtype with good survival and one in a high-risk subtype with poor survival. So the low-risk subtype should be the one that should be eligible for de-escalation therapy. And we took that low-risk subtype and tested it in a lab. And we found out that the low-risk subtype is intrinsically more sensitive to radiation therapy. So adding a mechanistic explanation as to why these subtypes are different. We did more work also that determined that the subtypes were determined by a different and new mechanism of HPV carcinogenesis that only occurs in head and neck cancer. So far, it’s only been identified in head and neck cancer. And this subtype has many molecular differences, including HPV is not integrated, somatic gene mutations and gene expression is different between the two subtypes. So the subtypes really are different molecularly, but most importantly for clinical use, they’re different in their survival and they’re different in their radiation treatment. So our goal is to move this forward into the clinic where we can take patients and appropriately identify patients who are better for de-escalation. So in other words, who can we treat with lower doses of radiation to avoid all of the side effects related with chemoradiation that our patients with head and neck cancer get? So we’re very excited about this data. That was the summary of the presentation. But we now have several publications out that sort of go over all of these aspects for people who are interested in going back to the base data.
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