ABSTRACT 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.
Williams et al. (Thu,) studied this question.