Introduction: The incidence of human papillomavirus 16 (HPV16)-associated head and neck squamous-cell carcinoma (HNC) is steadily rising. Intranasal neoadjuvant vaccines against HNC are a novel and potentially highly effective approach in cancer immunotherapy to directly induce broad humoral and cellular mucosal immunity.

Method: We utilized our previously reported Qβ-HPVag consisting of virus-like particles loaded with CPG and chemically coupled to four elongated HPV16-derived E6/E7 MHCI peptides for intranasal administration in an orthotopic murine model. Our study encompasses a range of in vivo and in vitro experiments, as well as tissue imaging mass cytometry (ongoing), to evaluate the immune cell populations within the tumor microenvironment.

Results: Our preliminary results indicated that intranasal administration of Qβ-HPVag impeded orthotopic tumor growth and enhanced the infiltration of tumor-infiltrating lymphocytes in the tumor. Assessment of vaccinated mouse lungs showed an increased CD8 T cell population, suggesting a protective potential of the intranasal vaccine. Moreover, our findings demonstrated improved tumor-free survival in the treated group after primary tumor dissection, indicating the efficacy of the neoadjuvant approach.

Conclusion: Our preliminary findings demonstrate the effectiveness of intranasal vaccination using Qβ-HPVag in an orthotopic murine model of aggressive head and neck cancer. These promising outcomes pave the way for novel clinical development strategies in HNC immunotherapy, suggesting a potential transformative impact on treatment paradigms.