Immune Cell Density Evaluation Improves the Prognostic Values of Staging and p16 in Oropharyngeal Cancer
by
,
Géraldine Descamps
1,
Sonia Furgiuele
1,
Nour Mhaidly
1,
Fabrice Journe
1,2,† and
Sven Saussez
1,3,*,†
1
Department of Human Anatomy and Experimental Oncology, Faculty of Medicine, Research Institute for Health Sciences and Technology, University of Mons (UMONS), Avenue du Champ de Mars, 8, B7000 Mons, Belgium
2
Laboratory of Clinical and Experimental Oncology, Institute Jules Bordet, Université Libre de Bruxelles (ULB), Rue Meylemeersch, 90, B1070 Anderlecht, Belgium
3
Department of Otolaryngology and Head and Neck Surgery, CHU Saint-Pierre, Rue aux Laines, 105, B1000 Brussels, Belgium
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2022, 14(22), 5560; https://doi.org/10.3390/cancers14225560
Submission received: 18 October 2022
/
Revised: 9 November 2022
/
Accepted: 11 November 2022
/
Published: 12 November 2022
(This article belongs to the Special Issue Human Papillomavirus and Head and Neck Cancer)
Simple Summary
Human papillomavirus (HPV) has become the major risk factor for the development of oropharyngeal squamous cell carcinomas (OPSCCs), the incidence of which continues to grow in Western countries. Their biological features, associated with a better prognosis as well as a greater response to treatment, has already led to their staging system reclassification and to the development of clinical trials to deintensify the therapeutic approaches. In this context, we proposed to evaluate the recruitment levels of immune cells to ameliorate the classification of some groups of OPSCCs that are always associated with poor outcomes. For this purpose, we scored the density of CD8 and FoxP3 lymphocytes, CD68 macrophages and CD1a Langerhans cells and associated the significant cells with either p16 status or TNM staging to create strong combinations that demonstrated powerful prognostic values in such patients. These results encourage the development of further studies based on the inclusion of immune criteria in the classification of OPSCCs.
Abstract
The incidence of oropharyngeal cancers (OPSCCs) has continued to rise over the years, mainly due to human papillomavirus (HPV) infection. Although they were newly reclassified in the last TNM staging system, some groups still relapse and have poor prognoses. Based on their implication in oncogenesis, we investigated the density of cytotoxic and regulatory T cells, macrophages, and Langerhans cells in relation to p16 status, staging and survival of patients. Biopsies from 194 OPSCCs were analyzed for HPV by RT-qPCR and for p16 by immunohistochemistry, while CD8, FoxP3, CD68 and CD1a immunolabeling was performed in stromal (ST) and intratumoral (IT) compartments to establish optimal cutoff values for overall survival (OS). High levels of FoxP3 IT and CD1a ST positively correlated with OS and were observed in p16-positive and low-stage patients, respectively. Then, their associations with p16 and TNM were more efficient than the clinical parameters alone in describing patient survival. Using multivariate analyses, we demonstrated that the respective combination of FoxP3 or CD1a with p16 status or staging was an independent prognostic marker improving the outcome of OPSCC patients. These two combinations are significant prognostic signatures that may eventually be included in the staging stratification system to develop personalized treatment approaches.
Keywords:
oropharyngeal cancer; p16; staging; TNM; prognostic; T regulatory lymphocytes; FoxP3; Langerhans cells; CD1a; immune cells
