Immunohistochemical analysis was performed to examine the infiltration of CD8<sup>+</sup>T cells, and anti-PD1 treatment was tested to evaluate its potential to prolong progression-free survival.<h4>Results</h4>In the HPV-positive HRAS-mutant HNSCC model, the antitumor efficacy of tipifarnib was primarily dependent on CD8<sup>+</sup>T cell activity, whereas in HPV-negative cancers, the contribution of antitumor immunity was less pronounced. Here, CD8A is linked to head and neck squamous cell carcinoma.