Mark Khoury, Alex Mlynarek, Keith Richardson, Nader Sadeghi, Michael Hier, Christina Tsien, George Shenouda, Khalil Sultanem, Nathaniel Bouganim, Khashayar Esfahani, Sabrina Wurzba, Marco Mascarella
LVI is associated with higher rates of distant metastasis and worse distant metastasis-free survival in operable HPV-negative HNSCC. However, this association is attenuated after adjustment for ENE and pN stage, suggesting that LVI may function as part of a broader adverse pathological phenotype rather than as an isolated independent predictor. These findings support the continued evaluation of LVI in postoperative risk stratification models.
BACKGROUND: Lymphovascular invasion (LVI) is a recognized poor prognostic factor in head and neck squamous cell carcinoma (HNSCC), particularly for regional recurrence and overall survival. However, its role in predicting distant metastasis, especially in HPV-negative HNSCC, remains unclear.
OBJECTIVE: To evaluate the association between LVI and distant metastasis in adult patients with operable HPV-negative HNSCC who underwent primary surgical resection.
METHODS: A retrospective analysis was conducted on 280 patients with HPV-negative HNSCC treated with primary surgery at two academic institutions from 2017 to 2024. Demographic, clinical, pathological, treatment, and outcome data were extracted. Kaplan-Meier analysis and multivariable Cox proportional hazards models were used to assess the association between LVI and distant metastasis-free survival.
RESULTS: Of the 280 patients, 94 (33.6%) were LVI-positive. Kaplan-Meier analysis demonstrated worse distant metastasis-free survival among patients with LVI-positive tumors, with separation persisting at 2 years (69.8% vs. 88.3%) and 3 years (63.1% vs. 87.4%). In multivariable Cox regression adjusting for age, sex, T stage, N stage, PNI, ENE, and margin status, the association between LVI and distant metastasis was attenuated and was not statistically significant (HR 1.56, 95% CI 0.88-2.77, p = 0.131). In a sensitivity model excluding N stage because of overlap with ENE, LVI remained associated with distant metastasis (HR 1.76, 95% CI 1.01-3.06, p = 0.047).
CONCLUSION: LVI is associated with higher rates of distant metastasis and worse distant metastasis-free survival in operable HPV-negative HNSCC. However, this association is attenuated after adjustment for ENE and pN stage, suggesting that LVI may function as part of a broader adverse pathological phenotype rather than as an isolated independent predictor. These findings support the continued evaluation of LVI in postoperative risk stratification models.