Descamps Géraldine, Furgiuele Sonia, Mhaidly Nour, Journe Fabrice, Saussez Sven
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.
Laboratory of Clinical and Experimental Oncology, Institute Jules Bordet, Université Libre de Bruxelles (ULB), Rue Meylemeersch, 90, B1070 Anderlecht, Belgium.
Cancers (Basel). 2022 Nov 12;14(22):5560. doi: 10.3390/cancers14225560.
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.
多年来，口咽癌（OPSCC）的发病率持续上升，主要原因是人类乳头瘤病毒（HPV）感染。尽管它们在最新的TNM分期系统中被重新分类，但仍有一些患者复发且预后较差。基于它们在肿瘤发生中的作用，我们研究了细胞毒性T细胞、调节性T细胞、巨噬细胞和朗格汉斯细胞的密度与患者的p16状态、分期及生存率之间的关系。对194例口咽癌活检样本进行逆转录定量聚合酶链反应（RT-qPCR）检测HPV，免疫组织化学检测p16，同时在基质（ST）和肿瘤内（IT）区域进行CD8、叉头框蛋白3（FoxP3）、CD68和CD1a免疫标记，以确定总生存期（OS）的最佳临界值。肿瘤内FoxP3高表达和基质CD1a高表达分别与OS呈正相关，且分别见于p16阳性和低分期患者。然后，在描述患者生存情况时，它们与p16和TNM的关联比单独的临床参数更有效。通过多变量分析，我们证明FoxP3或CD1a与p16状态或分期的各自组合是独立的预后标志物，可改善口咽癌患者的预后。这两种组合是重要的预后特征，最终可能会被纳入分期分层系统以制定个性化治疗方案。
