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Updated: Mar 28, 2026
Development of Compendium for Esophageal Squamous Cell Carcinoma
Published on: April 12, 2024
Biomarkers Associated With Extranodal Extension (ENE) in Oropharyngeal Squamous Cell Carcinoma (OPSCC): A Systematic
Lauren C Williams1, Naishaliz Lorenzo2, Alexander Ladenheim3
1Department of Surgery, Section of Otolaryngology, Head and Neck Surgery, Yale University School of Medicine, New Haven, Connecticut, USA.
Background:
Detection of extranodal extension (ENE) can guide treatment planning for patients with oropharyngeal squamous cell carcinoma (OPSCC). This systematic review identifies molecular biomarkers predictive of ENE in both Human Papillomavirus (HPV)-positive and HPV-negative OPSCC.
Methods:
A systematic review was conducted for relevant articles published between 1996 and July 2025. Studies were included if they included exclusively patients with OPSCC and evaluated the presence of ENE based on molecular biomarkers.
Results:
Ten studies met inclusion criteria. Tumor tissue modified viral (TTMV)-HPV DNA was not associated with ENE. Biomarkers associated with ENE included NOTCH-1 and WNT mutations and expression of podoplanin, Her3, and myoferlin. These biomarkers have also been linked with epithelial-mesenchymal transition (EMT) in cancer cells.
Conclusions:
Multiple genomic and molecular biomarkers have been identified in association with ENE in OPSCC, suggesting that ENE is characterized by an EMT phenotype.
