Head and neck squamous cell carcinoma (HNSCC) is a common malignancy with high rates of mortality and morbidity. Beginning with cetuximab, investigators continue to optimize antibody technology to target cell-surface receptors that promote HNSCC growth. Small molecules and oligonucleotides have also emerged as therapeutic inhibitors of key receptor-mediated signaling pathways. Although many such therapies have been disappointing in clinical trials as single agents, they continue to be studied in combination with standard therapies. Approvals of pembrolizumab and nivolumab opened a new era of immunotherapy that aims to stimulate antitumor immunity in the tumor microenvironment. Immunotherapies are being intensively investigated in new HNSCC clinical trials, with the goal of optimizing the therapeutic potential of this new class of anticancer agent.

Objective

Numerous pharmacological and cell-based treatments have shown promise in preventing vocal fold (VF) scarring when applied at the time of injury. A common clinical scenario, however, is the finding of mature scar impeding voicing. Many treatments are less effective in remodeling existing scar tissue. This objective of this study is to determine if a cell-based outer vocal fold replacement (COVR) effectively restores VF function when applied to existing scar.

Methods

Eighteen rabbits were allocated to three groups: unilateral COVR implant at the time of cordectomy (acute COVR); unilateral cordectomy followed by COVR implant 2 months later (chronic COVR); and unilateral cordectomy followed by sham implant surgery 2 months later (chronic scar). Larynges were harvested 2 months after implant or sham surgery.

Results

All larynges in the COVR groups demonstrated human leukocyte antigen labeling on immunohistochemistry (IHC). COVR groups had increased hyaluronic acid content compared with normal. VF stiffness as measured by elastic moduli in acute COVR and chronic COVR were similar to their contralateral unoperated VF.

Conclusion

COVR implantation in both acutely injured and chronically scarred VF demonstrate persistence of implanted cells, restored tissue biomechanics, and increased hyaluronic acid content.

Level of evidence

NA Laryngoscope, 134:764-772, 2024.