Abstract
BackgroundAlthough oropharyngeal squamous cell carcinoma (OPSCC) with human papillomavirus (HPV) infection has a good prognosis, the accurate prediction of survival and risk of treatment failure is essential to design deintensification regimens. Here, we investigated estrogen receptor α (ERα) as a prognostic biomarker with therapeutic implications in OPSCC alongside factors associated with HPV infection.MethodsWe performed immunohistochemistry for ERα and p53 using formalin-fixed, paraffin-embedded tissues and assessed the HPV status using p16 immunohistochemistry and HPV DNA testing in 113 consecutive patients with OPSCC treated with surgical resection or radiotherapy/chemoradiotherapy.ResultsERα expression and p53 alteration was observed in 35.4% and 21.2% OPSCCs; 45.6% and 1.3% p16+/HPV+ OPSCCs; and 11.5% and 76.9% p16− OPSCCs, respectively. These data suggest that OPSCC pathogenesis varies with HPV status. Furthermore, ERα expression was associated with improved overall survival (OS) in both HPV+ (p16+/HPV+ OPSCC) and p16+ (p16+ OPSCC irrespective of HPV status) models (p = 0.005 and p = 0.006, respectively) and with improved OS adjusted for stage (p = 0.037, hazard ratio: 0.109, 95% confidence interval 0.013–0.871) in the p16+ model.ConclusionsERα is a potential predictive biomarker for improved survival in both HPV+ and p16+ OPSCC models.
Highlights
Oropharyngeal squamous cell carcinoma (OPSCC) with human papillomavirus (HPV) infec‐ tion has a good prognosis, the accurate prediction of survival and risk of treatment failure is essential to design dein‐ tensification regimens
Most p16+/HPV+ tumors occurred in the palatine tonsil and base of tongue, but p16− tumors occurred in various subsites such as pharyngeal walls, soft palates, and uvula, thereby showing significant differences in tumor origin (p < 0.001)
estrogen receptor α (ERα) expression was restricted to the subsets of basal cells of the non-neoplastic squamous epithelium around the tumor, and this expression was present irrespective of the HPV status of the tumor in 15 out of 80 resected specimens (Fig. 2a)
Summary
Oropharyngeal squamous cell carcinoma (OPSCC) with human papillomavirus (HPV) infec‐ tion has a good prognosis, the accurate prediction of survival and risk of treatment failure is essential to design dein‐ tensification regimens. We investigated estrogen receptor α (ERα) as a prognostic biomarker with therapeutic implications in OPSCC alongside factors associated with HPV infection. Estrogen receptors (ERs) exist in two isoforms, ERα and ERβ These isoforms trigger distinct transcriptional responses and exert opposite effects on cellular processes, including proliferation, apoptosis, migration, and other processes that differentially influence cancer development and progression [15]. ERα was significantly associated with improved overall survival (OS) in patients with HPV+ OPSCC [20] This prognostic implication of ERα in HPV+ OPSCC is considerably different from the known role of ERα in HPV+ cervical cancer
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