Characterization of differences in the immune response against two types of HPV-induced malignancies - cervical carcinoma and head and neck squamous cell carcinoma

Introduction: Human papillomaviruses (HPV) are responsible for more than 1 400 000 new cancer cases each year. Patients with HPV-associated oropharyngeal cancers have a significantly better prognosis than patients with cancers of other etiologies. An unanswered question is whether the antitumor immune response in tumors related to infection with high-risk HPV types is driven primarily by viral infection or rather by tumor localization and specific tumor microenvironment. Methods: To answer this question, we analyzed the immune milieu of two HPV-associated malignancies: oropharyngeal squamous cell carcinoma (OPSCC) and cervical squamous cell carcinoma (CESC). We used multiplex immunohistochemistry and immunofluorescence for this analysis. We evaluated the density and spatial distribution of immune cells in retrospective cohorts of patients with OPSCC and CESC. This approach was complemented by analysis of prospective cohorts of patients with OPSCC and CESC. After processing native tumor tissue samples, we performed transcriptomic analysis of purified primary tumor cells and in silico analysis of publicly available RNA sequencing data. Results: Transcriptomic analysis showed similar immune profiles in OPSCC and CESC samples. Interestingly, immunostaining of OPSCC tissues revealed a high density of...