The Immune Landscape of HPV-Associated Head and Neck Cancer

Objectives: To conduct a comprehensive genomic analysis of head and neck squamous cell carcinoma(HNSCC) to shape tumor microenvironment and to develop a rationale for immunotherapeutic strategies of HNSCC.
Methods: Gene-level RSEM-normalized RNA-seq data and the clinical annotation for TCGA HNSCC cohort were collected from GDAC firebrowse. Infiltration scores of immune cells were estimated by TIMER method. The number of clonotypes and the CDR3 motif was calculated by TRUST algorithm.
Results: HPV+ patients have a better clinical outcome comparing with HPV- patients. Consensus hierarchical clustering analysis using microenvironment signature genes which are negatively correlated with purity shows that two remarkable clusters are consistent with HPV infection, indicating HPV as a major factor in the tumor microenvironment. HPV+ tumors have higher abundance of immune infiltrating cells, including CD8+ T cells, CD4+ T cells, B cells and dendritic cells. Moreover, HPV+ tumors have higher T cell receptor diversity and exhibit a distinct TCR pattern and CDR3 motifs. With higher infiltrating immune cells, HPV+ tumors have a higher expression level of most immune checkpoint molecular. Also, analyzing correlations between all genes' expression with immune exclusion signature of fibroblasts and MDSCs, we found higher correlations in HPV- patients, suggesting that these patients have denser stroma and alternative myeloid cell population, which would potentially impede anti-tumor immune response. Furthermore, in HPV+ patients, the clinical outcome could benefit from CD8 expression significantly, but not in HPV- patients.
Conclusions: These analyses illuminate HPV infection is associated with a robust immune response in HNSCC patients, indicating that HPV+ patients would have better clinical benefits for immunotherapies.