Association of Estrogen Receptor Alpha Expression With Survival in Oropharyngeal Cancer Following Chemoradiation Therapy

J Natl Cancer Inst. 2019 Sep 1;111(9):933-942. doi: 10.1093/jnci/djy224.


Background: Oropharyngeal squamous carcinoma (OPSC) continues to increase in incidence secondary to human papillomavirus (HPV) infection. Despite the good overall prognosis for these patients, treatment with chemoradiation is associated with morbidity and treatment failure. Better predictors for disease outcome are needed to guide de-intensification regimens. We hypothesized that estrogen receptor α (ERα), a prognostic biomarker in oncology with therapeutic implications, might have similar utility in OPSC.

Methods: To investigate associations among ERα and demographics, HPV status, and survival, we analyzed ERα mRNA expression of head and neck squamous carcinomas (HNSC) from The Cancer Genome Atlas (TCGA) and immunohistochemistry (IHC) of pretreatment biopsy specimens from an independent group of 215 OPSC patients subsequently treated with primary chemoradiation (OPSC-CR). Associations among variables were evaluated with Fisher exact tests and logistic regression; associations with survival were evaluated with log-rank tests and Cox proportional hazards regression.

Results: Among 515 patients in TCGA, ERα mRNA expression was highest in HPV-positive OPSC. High ERα mRNA expression was associated with improved survival among those receiving chemoradiation (hazard ratio adjusted for HPV status = 0.44, 95% confidence interval = 0.21 to 0.92). In OPSC-CR, ERα was positive by IHC in 51.6% of tumors and was associated with improved overall, disease-specific, progression-free, and relapse-free survival (log-rank tests: P < .001, P < .001, P = .002, P = .003, respectively); statistically significant associations of ERα positivity with improved survival were maintained after adjusting for clinical risk factors including HPV status.

Conclusion: In two independent cohorts, ERα is a potential biomarker for improved survival that also may represent a therapeutic target in OPSC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor*
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / therapy
  • Chemoradiotherapy
  • Estrogen Receptor alpha / genetics*
  • Estrogen Receptor alpha / metabolism
  • Female
  • Gene Expression*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Oropharyngeal Neoplasms / diagnosis
  • Oropharyngeal Neoplasms / genetics*
  • Oropharyngeal Neoplasms / mortality*
  • Oropharyngeal Neoplasms / therapy
  • Prognosis
  • Proportional Hazards Models
  • Signal Transduction


  • Biomarkers, Tumor
  • ESR1 protein, human
  • Estrogen Receptor alpha