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Top Line: Just when you think you have down the HPV-based risk stratification scheme for oropharyngeal cancer.
The Study: This very interesting study investigated the significance of estrogen receptor (ER)-positivity among hundreds of head and neck (H&N) tumors. Yep, the same ole ER-immunohistochemistry used in breast cancer was retrospectively used on a large cohort of oropharyngeal tumors. About half were ER(+), but among HPV(+) tumors, specifically, 60% were ER(+) compared to just 20% for HPV(-) tumors. While we already know patients with HPV(+) tumors have good outcomes, patients with HPV(+), ER(+) tumors have even better outcomes with a significant improvement in overall survival independent of HPV-positivity. These findings were supported with a separate larger cohort on H&N tumors in the Cancer Genome Atlas (TCGA). This is big news for two reasons. Sure, we get another prognostic marker. But in contrast to HPV, this marker could offer up an actual therapeutic target. The details of this association aren’t well understood at this point, although there is speculation that ER-signalling may modulate transcription of HPV-DNA. 
Bottom Line: ER-positivity in HPV(+) oropharyngeal cancer is associated with particularly superior survival outcomes and may one day prove a therapeutic target. | Koenigs, J Natl Cancer Inst 2019

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