Koenigs MB, et al. - Researchers investigated if estrogen receptor α (ERα), a prognostic biomarker in oncology with therapeutic implications, could have similar utility in oropharyngeal squamous carcinoma (OPSC). They used The Cancer Genome Atlas (TCGA) to assess associations among ERα and demographics, human papillomavirus (HPV) status, and survival by analyzing ERα mRNA expression of head and neck squamous carcinomas (HNSC). Also, they analyzed immunohistochemistry (IHC) of pretreatment biopsy specimens from an independent group of 215 OPSC patients subsequently treated with primary chemoradiation (OPSC-CR). Among 515 patients in TCGA, improved survival was observed in relation to high ERα mRNA expression in those receiving chemoradiation. In 51.6% of tumors in OPSC-CR, IHC revealed ERα positivity and relation of ERα to improved overall, disease-specific, progression-free, and relapse-free survival. Findings revealed the utility of ERα as a potential biomarker for improved survival in two independent cohorts. It could be a therapeutic target in OPSC.