Implications and Emerging Therapeutic Avenues of Inflammatory Response in HPV+ Head and Neck Squamous Cell Carcinoma

Abstract

Head and neck squamous cell carcinomas (HNSCC) are a heterogeneous group of malignancies which have shown exponential incidence in the last two decades especially due to human papillomavirus (HPV) infection. The HPV family comprises more than 100 types of viruses with HPV16 and HPV18 being the most prevalent strains in HNSCC. Literature data reveal that the mutation profile as well as the response to chemotherapy and radiotherapy are distinct among HPV+ versus HPV-negative tumors. Furthermore, the presence of the virus induces activation of an immune response, in particular the recruitment of specific antiviral T lymphocytes to tumor sites. These T cells when activated produce soluble factors including cytokines and chemokines capable of modifying the local immune tumor microenvironment and impact on tumor response to the treatment. In this comprehensive review we investigated current knowledge on how the presence of an HPV can modify the inflammatory response systemically and within the tumor microenvironment’s immunological responses, thereby impacting on disease prognosis and survival. We highlighted the research gaps and emerging approaches necessary to discover novel immunotherapeutic targets for HPV-associated HNSCC.

Novel Immunotherapeutic Approaches to Treating HPV-Related Head and Neck Cancer

“… HPV-related head and neck squamous cell carcinoma tumor microenvironment [ 53 ]. Key: Figure adopted with permission from SD da Silva, corresponding author of the manuscript “Implications and Emerging Therapeutic Avenues of Inflammatory Response in HPV+ Head and Neck Squamous Cell Carcinoma”.…”

Serine and one-carbon metabolism sustain non-melanoma skin cancer progression

“…HNSCCs are the sixth most common cancer worldwide [26]. Tobacco and alcohol are the primary risk factors, as well as virus infection [27][28][29][30]. Similarly to cSCCs, HNSCC incidence is continuously rising, and it is expected to increase by 30% by 2030.…”

A novel immune-related prognostic model with surgical status to predict tumor immune cell infiltration and drug sensitivity in head and neck squamous cell carcinoma

“…The tumor microenvironment (TME) is a complex entity that plays an important role in HNSCC tumorigenesis and tumor growth, progression, and treatment response. It includes the extracellular matrix, cancer-associated fibroblasts, and various tumor-infiltrating immune cell (TIC) subtypes [ 7 , 8 ]. TICs interact with tumor cells to form a supporting environment and produce hormone-like bioregulators to affect homeostasis locally and systematically, preventing the body's anticancer activity and enhancing tumor growth [ 9 ].…”

“…However, surgery and radiochemotherapy could substantially disrupt tissues and vessels and change the TIC component in HNSCC, exacerbating preexisting immunosuppressive effects [ 5 , 7 ]. The OS prediction accuracy of previously published models was established based on immune-related signatures, and the usefulness of tumor stage and grade was limited in patients with HNSCC.…”