Augustin Jeremy Gbenakpon, Lepine Charles, Morini Aurelien, Brunet Anais, Veyer David, Brochard Camille, Mirghani Haitham, Péré Hélène, Badoual Cécile
Department of Pathology, Henri Mondor Hospital, APHP, Créteil, France.
Department of Pathology, European Georges Pompidou Hospital, APHP, Université de Paris, Paris, France.
Front Oncol. 2020 Sep 15;10:1751. doi: 10.3389/fonc.2020.01751. eCollection 2020.
Besides classic tobacco and alcohol risk factors, human papillomavirus (HPV) plays a role in the development of a subset of head and neck squamous cell carcinomas (HNSCCs), and notably oropharynx squamous cell carcinomas (OPSCCs). HPV-induced OPSCCs have a different biological behavior and a better prognosis compared to non-HPV-induced OPSCCs and the eighth-edition TNM classification now separates these two entities. Therefore, determining the HPV status of patients with OPSCC is now essential for treatment, prognosis, and development of clinical trials. In this review, after reminding essential steps of HPV implication in the cell cycle, we describe the existing tools that are currently feasible in routine practice according to facilities available in health structures, with their benefits and drawbacks: HPV PCR, E6/E7 mRNA RT-PCR, E6/E7 mRNA hybridization, HPV DNA hybridization, and P16 immunochemistry. Besides these traditional HPV detection tools, novel diagnostic approaches are being evaluated for HPV-induced OPSCC "ultrastaging." E6 humoral response and ddPCR-detecting HPVct DNA are two techniques performed on blood and are therefore non-invasive. Baseline E6 humoral levels could have a prognostic value, and HPVct DNA could be helpful for HPV OPSCC recurrence monitoring. At last, next-generation sequencing (NGS)-based "capture HPV" is a technique feasible on biopsies and circulating DNA material. It helps characterize HPV integration status and sites, and it could define prognostic subgroups in HPV-induced OPSCC. These novel precision detection tools could be further integrated in the care of patients with HPV-induced OPSCC.
除了经典的烟草和酒精风险因素外,人乳头瘤病毒(HPV)在一部分头颈部鳞状细胞癌(HNSCC)尤其是口咽鳞状细胞癌(OPSCC)的发生发展中起作用。与非HPV诱导的OPSCC相比,HPV诱导的OPSCC具有不同的生物学行为和更好的预后,第八版TNM分类现在将这两种实体区分开来。因此,确定OPSCC患者的HPV状态对于治疗、预后以及临床试验的开展至关重要。在这篇综述中,在回顾了HPV影响细胞周期的基本步骤后,我们根据卫生机构可用的设施描述了目前在常规实践中可行的现有工具,及其优缺点:HPV PCR、E6/E7 mRNA RT-PCR、E6/E7 mRNA杂交、HPV DNA杂交和P16免疫化学。除了这些传统的HPV检测工具外,正在评估用于HPV诱导的OPSCC“超分期”的新型诊断方法。E6体液反应和检测HPVct DNA的数字滴度PCR(ddPCR)是两种在血液上进行的技术,因此是非侵入性的。基线E6体液水平可能具有预后价值,而HPVct DNA可能有助于HPV OPSCC复发监测。最后,基于下一代测序(NGS)的“捕获HPV”是一种在活检组织和循环DNA材料上可行的技术。它有助于表征HPV整合状态和位点,并可定义HPV诱导的OPSCC的预后亚组。这些新型的精确检测工具可以进一步整合到HPV诱导的OPSCC患者的护理中。