Department of Medical, Surgical and Health Sciences, Section of Otolaryngology, University of Trieste, Trieste, Italy.
Unit of Cancer Epidemiology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy.
Head Neck Pathol. 2024 Oct 15;18(1):101. doi: 10.1007/s12105-024-01713-7.
Accuracy in the diagnosis of HPV-associated oropharyngeal carcinoma (OPSCC) of a rapid, low-cost lateral flow immunochromatographic assay for detecting E6 oncoprotein of HPV-16 and HPV-18 was previously evaluated in a small pilot study. This cross-sectional study aimed to assess on a large case series the sensitivity and specificity of E6 oncoprotein as a diagnostic marker for HPV-associated carcinogenesis in OPSCC.
137 consecutive patients with histologically confirmed OPSCC were enrolled in two hospitals in Northeast Italy. HPV status was determined by PCR for HPV DNA and p16 immunohistochemistry on primary tumor biopsies. An OPSCC was defined as HPV-associated when double positive for high-risk HPV-DNA and p16 overexpression in primary lesion. Cytological samples from primary tumors and metastatic lymph nodes were obtained and tested for HPV16/18 E6 oncoproteins using the lateral flow immunochromatographic assay, which requires between 90 and 120 min to provide a result. Diagnostic performances were calculated as percentage with confidence intervals (CI).
Of the 137 OPSCC cases, 68 (49.6%) were HPV-associated, testing positive for both high-risk HPV-DNA and p16, with HPV16 predominating (82.4%). An average waiting time of 22 days was observed to obtain the results of p16 and HPV-DNA after primary lesions biopsy. In patients with HPV16/18-associated OPSCC, the HPV16/18 E6 oncoprotein was detected in 59 out of 60 cytological samples from the primary lesion (sensitivity: 98.3%; 95% CI: 91.1-100%) and in 45 out of 51 cytological samples from lymph node metastases (sensitivity: 88.2%; 95% CI: 76.1-95.6%). The E6 oncoprotein assay showed a specificity of 100% in both primary tumors and lymph node metastases.
The low-cost lateral flow immunochromatographic assay for detecting HPV16/18 E6 oncoproteins confirmed high accuracy for identifying HPV-associated OPSCC, particularly in primary tumors, suggesting its potential as a valuable diagnostic tool in clinical practice. Its rapid diagnostic capability could significantly accelerate the process of treatment decision-making, enhancing the timely management of patients.
先前在一项小型试点研究中评估了一种用于检测 HPV-16 和 HPV-18 E6 癌蛋白的快速、低成本侧向流动免疫层析检测法在 HPV 相关口咽癌 (OPSCC) 诊断中的准确性。本横断面研究旨在通过大病例系列评估 E6 癌蛋白作为 OPSCC 中 HPV 相关致癌作用的诊断标志物的敏感性和特异性。
在意大利东北部的两家医院共纳入了 137 例经组织学证实的 OPSCC 患者。通过聚合酶链反应 (PCR) 检测 HPV DNA 和原发性肿瘤活检的 p16 免疫组化来确定 HPV 状态。当高危型 HPV-DNA 和原发性病变中 p16 过表达双重阳性时，将 OPSCC 定义为 HPV 相关。从原发性肿瘤和转移性淋巴结获得细胞学样本，并使用侧向流动免疫层析法检测 HPV16/18 E6 癌蛋白，该检测法需要 90-120 分钟才能得出结果。计算诊断性能的百分比及其置信区间 (CI)。
在 137 例 OPSCC 病例中，68 例 (49.6%) 为 HPV 相关，对高危型 HPV-DNA 和 p16 均呈阳性，其中 HPV16 占主导地位 (82.4%)。在获得原发性病变活检后，p16 和 HPV-DNA 的结果平均需要等待 22 天。在 HPV16/18 相关 OPSCC 患者中，60 例原发性病变细胞学样本中 59 例 (敏感性：98.3%；95%CI：91.1-100%) 和 51 例淋巴结转移细胞学样本中 45 例 (敏感性：88.2%；95%CI：76.1-95.6%) 检测到 HPV16/18 E6 癌蛋白。E6 癌蛋白检测在原发性肿瘤和淋巴结转移中均显示出 100%的特异性。
用于检测 HPV16/18 E6 癌蛋白的低成本侧向流动免疫层析检测法证实了其在识别 HPV 相关 OPSCC 方面的高准确性，特别是在原发性肿瘤中，提示其具有作为临床实践中一种有价值的诊断工具的潜力。其快速诊断能力可显著加快治疗决策过程，及时管理患者。
