Pre-Operative Nodal Biopsy and Extranodal Extension in p16+ Oropharyngeal Squamous Cell Carcinoma

CLINICAL QUESTION

Does the type of pre-operative nodal biopsy influence the risk of extra nodal extension (ENE) in patients with p16-positive oropharyngeal squamous cell carcinoma (OPSCC), and is it associated with adjuvant therapy type?

BOTTOM LINE

In this retrospective cohort study, pre-operative core needle biopsy (CNB) was not significantly associated with an increased risk of ENE in patients undergoing surgery for p16-positive OPSCC. Fine needle aspiration (FNA) and CNB also had no association with the likelihood of requiring adjuvant chemoradiotherapy.

BACKGROUND: Extranodal extension is a critical prognostic factor in head and neck cancers, particularly p16-positive OPSCC. It is often used to guide adjuvant chemoradiotherapy. Concerns exist that CNB, by disrupting lymph node capsules, may artificially increase ENE detection, potentially affecting treatment plans.

STUDY DESIGN: Retrospective cohort study of patients with p16-positive OPSCC who underwent transoral robotic surgery (TORS) and neck dissection. Logistic regression analyses were used to assess the relationship between biopsy type and ENE.

SETTING: Single tertiary care center (Vanderbilt University Medical Center, Nashville, Tenn.), over a period from October 2011 to March 2025

SYNOPSIS: The study analyzed 123 patients with p16-positive OPSCC (mean age 60.9 years; 91.1% male). Of these, 16 underwent CNB, 74 underwent FNA, and 33 had no pre-operative nodal biopsy. Forty-three patients (35% overall) had ENE, including 43.8% of those who had CNB, 37.8% with FNA, and 24.2% with no biopsy. However, neither CNB nor FNA was significantly associated with ENE on univariate or multivariate logistic regression. Additionally, the type of biopsy did not influence whether patients received adjuvant radiotherapy or chemoradiotherapy. The American Joint Committee on Cancer 7th edition cN2b classification (≥2 clinically positive nodes) showed the highest association with ENE (48.6%), suggesting tumor burden rather than biopsy type may be a stronger predictor. The authors highlight limitations, including a small CNB sample size, retrospective design, and single-institution bias. They suggest further research through multi-institutional studies.

CITATION: Sridhar S, et al. Preoperative nodal biopsy and extranodal extension in p16+ oropharyngeal squamous cell carcinoma. Laryngoscope Investig Otolaryngol. 2025;10:e70150. doi:10.1002/lio2.70150