Immuno-Oncological Biomarkers for Squamous Cell Cancer of the Head and Neck: Current State of the Art and Future Perspectives

Abstract

The era of immune checkpoint inhibitors has altered the therapeutic landscape in squamous cell cancer of the head and neck (SCCHN). Our knowledge about the tumor microenvironment has fueled the research in SCCHN, leading to several well-known and less-known prognostic and predictive biomarkers. The clinical staging, p16/HPV status, and PD-L1 expression are currently the main tools for assessing the patients’ diagnosis and prognosis. However, several novel biomarkers have been thoroughly investigated, some reaching actual significant clinical contributions. The untangling of the immune infiltrate with the subtyping of tissue-associated tumor infiltrating lymphocytes, tumor-associated macrophages, and circulating blood-based biomarkers are an interesting avenue to be further explored and prospectively assessed. Although PD-L1 expression remains the most important response predictor for immune checkpoint inhibitors, several flaws impede proper assessment such as technical issues, different scoring protocol, and intra-, inter,- and temporal heterogeneity. In addition, the construction of an immune-related gene panel has been proposed as a prognostic and predictive stratification but lacks consensus. Recently, the role of microbioma have also been explored regarding its systemic and antitumor immunity. This review gives a comprehensive overview of the aforementioned topics in SCCHN. To this end, the integration of these clinically advantageous biomarkers via construction of an immunogram or nomogram could be an invaluable tool for SCCHN in future prospects.

Haemophilus pittmaniae and Leptotrichia spp. Constitute a Multi-Marker Signature in a Cohort of Human Papillomavirus-Positive Head and Neck Cancer Patients

“…While little is known about H. pittmaniae and its role in periodontal disease, the Haemophilus genus was identified in many positively classified studies per our LitSuggest text mining analysis. In a recent study by De Keukeleire et al (2021) a decrease in Haemophilus was associated with HNC-SCC, confirming findings by Wolf et al (2017) and Lim et al (2018) . However, studies by Guerrero-Preston et al (2016) and Gougousis et al (2021) found the opposite to be true.…”

Tumor HPV Status, Level of Regulatory T Cells and Macrophage Infiltration Predict up to 20-Year Non-Disease-Specific Survival in Oropharynx Squamous Cell Carcinoma Patients

“…In a review paper, the IL-6 serum level at diagnosis was significantly correlated to survival in 82/101 series comprising 9917 out of 11,583 patients with 23 different cancer types [ 24 ], including HNSCC [ 25 ] patients. We [ 26 , 27 ] and others [ 6 ] have also shown an association between monocyte tumor reactivity and HNSCC prognosis. We therefore aimed to study the level of macrophages as measured by CD68-positive cell infiltration in the studied OPSCC tumors in relation to long-term prognosis.…”

“…We have previously studied, in particular, oropharyngeal SCC (OPSCC), and therefore find it pertinent presently to use such patients. An advantage with this disease origin is that one may include investigation of different profiles between HPV-caused SCC versus OPSCC generated by tobacco and alcohol consumption [ 6 ]. These two different causes generate OPSCC with different tumor immune infiltration, histological malignancy degree and prognosis [ 7 ].…”

Prognostic Significance of PD-L1 Expression In Patients With Primary Oropharyngeal Squamous Cell Carcinoma: A Meta-Analysis

“…Although HPV oncoproteins E5 and E6/E7 were supposed to activate the PD-1/PD-L1 axis ( 50 ), further research is required to elucidate the association between HPV oncoproteins and PD-L1. In addition, since PD-L1 gets up-regulated in response to tumor-infiltrating lymphocytes (TIL)-derived cytokines, the increase in PD-L1 expression in HPV-positive OPSCC might be related to a more inflamed tumor microenvironment with recruitment of TILs, rather than to a direct causative effect of HPV on PD-L1 expression ( 51 ). This theory is in line with the evidence that abundant TILs and high PD-L1 expression in intratumoral immune cells identified subgroups of HPV-positive OPSCC patients with excellent outcomes ( 27 ).…”