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Nectin-4 has been successfully established as a target molecule in locally advanced and metastatic bladder cancer. An antibody-drug conjugate (enfortumab-vedotin) directed against nectin-4 has shown marked tumor remission rates in this tumor type, which is known for high expression rates of nectin-4.

As head and neck cancer and urothelial carcinomas share morphological and molecular similarities, researchers Christine Sanders, Jan-Frederic Lau, Dimo Dietrich, Sebastian Strieth, Peter Brossart, and Glen Kristiansen from University Medical Center Bonn and University Hospital Bonn aimed to evaluate Nectin-4 expression in head and neck squamous cell carcinoma (HNSCC).

A previously described and clinically characterized cohort of HNSCC (n = 159) was analyzed by immunohistochemistry for Nectin-4 expression. The expression data was correlated to clinico-pathological parameters including patient outcome.

Nectin-4 was found in 86.2% of HNSCC, with medium/high expression seen in 32.7% of cases. Non-smokers and p16 positive HNSCC showed a higher expression of Nectin-4 (p < 0.005). There was no correlation of Nectin-4 with grading or tumor stage. Nectin-4 positive tumors showed significantly better survival (log rank p = 0.006).

“Similar to urothelial carcinoma, Nectin-4 is found in the majority of HNSCC, which clearly warrants further studies to clarify if HNSCC also respond to targeted therapy with enfortumab-vedotin. Moreover, expression of Nectin-4 is associated with HPV infection and may serve as a prognostic marker in HNSCC.”