Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Background: Locally advanced oropharyngeal squamous cell carcinoma (OPSCC) can be treated with either chemoradiation or primary surgery +/- adjuvant treatment. The presence of clinical extranodal extension (ENE) preoperatively is an indication for chemoradiation (CRT), however clinically occult ENE is difficult to identify without histopathological analysis following surgery. Identification of molecular biomarkers associated with ENE would enable more accurate prediction of occult ENE prior to surgery and would decrease the need for trimodality therapy in this population.
Objective: This systematic review aimed to identify histopathologic and genomic biomarkers predictive of extranodal extension in OPSCC, given its importance for treatment planning, particularly in determining whether patients with locally advanced OPSCC should undergo upfront surgery or definitive chemoradiotherapy (CRT).
Methods: A systematic search of four electronic databases—Embase, Scopus, PubMed, and Web of Science—was conducted for relevant articles published between 1996 and June 2024. After removing duplicates, 561 studies were identified. A total of 66 full-text articles were assessed for eligibility. Two independent reviewers screened the studies and evaluated the risk of bias. Studies on cancers other than OPSCC or those not examining histopathologic or genomic biomarkers were excluded.
Results: Nine studies met the inclusion criteria. The identified biomarkers predictive of ENE included cell-free HPV DNA in both plasma and surgical drain fluid in HPV-positive OPSCC. Podoplanin expression as well as WNT and NOTCH-1 pathway mutations were also associated with ENE in HPV-positive OPSCC. Biomarkers associated with ENE in HPV-negative OPSCC included HER3 and myoferlin expression.
Conclusion: Multiple genomic and proteomic markers have been identified that are associated with ENE in both HPV-positive and HPV-negative OPSCC. Biomarkers predictive of ENE differed based on HPV status. Further investigation is needed to validate these studies and to identify molecular and genomic biomarkers that can be performed at the time of diagnosis to guide treatment planning for patients with OPSCC.