Neoadjuvant Chemotherapy Enhances Tumor-specific T Cell Immunity in Patients with HPV-associated Oropharyngeal Cancer

Background: Treatment of patients with newly diagnosed HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) with neoadjuvant chemotherapy (NAC) results in a high rate of 5-year recurrence free survival with few patients requiring adjuvant treatment. We hypothesized that NAC enhances primary tumor HPV-specific T cell responses.

Methods: HPV-specific responses in tumor infiltrating lymphocytes (TILs) before and after NAC were determined using autologous co-culture assays.

Results: Greater HPV16-specific TIL responses, sometimes polyclonal, were observed after NAC compared to before in 8 of 10 patients (80%) with PCR-verified HPV16-positive tumors. A significant association was observed between net-negative change in HPV-specific TIL response and disease relapse (p = 0.04, Mann-Whitney test), whereas pathologic complete response at time of surgery did not correlate with recurrence.

Conclusions: NAC induces HPV-specific tumor T cell responses in patients with newly diagnosed HPV-associated OPSCC; whereas lack of an increase following NAC may associate with risk of relapse.