HPV-16 病毒载量对口咽鳞癌的预后影响。

Prognostic impact of intra tumoral HPV-16 viral load in oropharyngeal squamous cell carcinomas.

机构信息

Department of Head and Neck Surgery, Antoine Lacassagne Centre, University Institute of the Face and Neck, Nice, France; Université Côte d'Azur, Antoine Lacassagne Centre, Laboratory of Translational Research in Oncology, Nice, France.

Université Côte d'Azur, Antoine Lacassagne Centre, Laboratory of Translational Research in Oncology, Nice, France; Oncopharmacology Laboratory, Antoine Lacassagne Centre, Nice, France.

出版信息

Oral Oncol. 2024 Dec;159:107082. doi: 10.1016/j.oraloncology.2024.107082. Epub 2024 Oct 28.

DOI:10.1016/j.oraloncology.2024.107082

PMID:39467340

Abstract

OBJECTIVES

The incidence of HPV-induced oropharyngeal squamous cell carcinoma (OSCC) is constantly increasing. Although HPV-related OSCC carry a better prognosis, the majority of patients with an HPV-positive OSCC have other prognostic factors such as tobacco smoking, making therapeutic de-escalating approaches less precise. In this context, our study aims to evaluate the prognostic impact of intra-tumoral HPV-16 viral load (VL) in OSCC.

MATERIAL AND METHODS

We conducted a retrospective analysis of p16-positive OSCC samples from patients treated between 2012 and 2019. Viral load (VL) was determined using digital droplet Polymerase Chain Reaction (ddPCR) and described according to 3 subgroups: low (<0.9 copies/cell), medium (0.9-85 copies/cell), and high (>85 copies/cell). We assessed the correlation between VL and recurrence-free survival (RFS), specific survival (SS), and overall survival (OS) using the Kaplan-Meier method.

RESULTS

In total, 192 patients were included; 148 (77 %) were male. The mean age was 65. HPV-16 was detected in 189/192 samples (98 %). T3-4-stage (p = 0.002), metastasis (p = 0.007), and tobacco consumption (p = 0.01) predicted lower OS. High VL was associated with higher RFS (HR = 0.2, p = 0.01), SS (HR = 0.32, p = 0.02), and OS (HR = 0.39, p = 0.03). After adjusting for tobacco consumption and tumor stage, high VL remained associated with higher RFS (HR = 0.1, 95 %CI [0.04-0.7], p = 0.01) and SS (HR = 0.20, 95 %CI [0.05-0.75], p = 0.01).

CONCLUSION

In our study, high intra-tumoral HPV VL was independently associated with survival. Subject to further validation in independent and prospective cohorts, our findings suggest that HPV VL could help to refine the prognosis of HPV positive OSCC patients.

摘要

目的

人乳头瘤病毒（HPV）诱导的口咽鳞状细胞癌（OSCC）的发病率不断上升。尽管 HPV 相关 OSCC 的预后较好，但大多数 HPV 阳性 OSCC 患者存在其他预后因素，如吸烟，这使得治疗降级方法不够精确。在这种情况下，我们的研究旨在评估 OSCC 中肿瘤内 HPV-16 病毒载量（VL）的预后影响。

材料和方法

我们对 2012 年至 2019 年期间治疗的 p16 阳性 OSCC 患者样本进行了回顾性分析。使用数字液滴聚合酶链反应（ddPCR）测定病毒载量（VL），并根据 3 个亚组进行描述：低（<0.9 拷贝/细胞）、中（0.9-85 拷贝/细胞）和高（>85 拷贝/细胞）。我们使用 Kaplan-Meier 方法评估 VL 与无复发生存率（RFS）、特异性生存率（SS）和总生存率（OS）之间的相关性。

结果

共纳入 192 例患者，其中 148 例（77%）为男性。平均年龄为 65 岁。192 例样本中 189 例（98%）检测到 HPV-16。T3-4 期（p=0.002）、转移（p=0.007）和吸烟（p=0.01）预测 OS 较低。高 VL 与更高的 RFS（HR=0.2，p=0.01）、SS（HR=0.32，p=0.02）和 OS（HR=0.39，p=0.03）相关。在调整吸烟和肿瘤分期后，高 VL 仍与更高的 RFS（HR=0.1，95%CI [0.04-0.7]，p=0.01）和 SS（HR=0.20，95%CI [0.05-0.75]，p=0.01）相关。