Holzinger Dana, Wichmann Gunnar, Baboci Lorena, Michel Angelika, Höfler Daniela, Wiesenfarth Manuel, Schroeder Lea, Boscolo-Rizzo Paolo, Herold-Mende Christel, Dyckhoff Gerhard, Boehm Andreas, Del Mistro Annarosa, Bosch Franz X, Dietz Andreas, Pawlita Michael, Waterboer Tim
Division of Molecular Diagnostics of Oncogenic Infections, Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Otorhinolaryngology, University Hospital Leipzig, Leipzig, Germany.
Int J Cancer. 2017 Jun 15;140(12):2748-2757. doi: 10.1002/ijc.30697. Epub 2017 Apr 4.
To determine the sensitivity and specificity of HPV16 serology as diagnostic marker for HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), 214 HNSCC patients from Germany and Italy with fresh-frozen tumor tissues and sera collected before treatment were included in this study. Hundred and twenty cancer cases were from the oropharynx and 94 were from head and neck cancer regions outside the oropharynx (45 oral cavity, 12 hypopharynx and 35 larynx). Serum antibodies to early (E1, E2, E6 and E7) and late (L1) HPV16 proteins were analyzed by multiplex serology and were compared to tumor HPV RNA status as the gold standard. A tumor was defined as HPV-driven in the presence of HPV16 DNA and HPV16 transformation-specific RNA transcript patterns (E6*I, E1 E4 and E1C). Of 120 OPSCC, 66 (55%) were HPV16-driven. HPV16 E6 seropositivity was the best predictor of HPV16-driven OPSCC (diagnostic accuracy 97% [95%CI 92-99%], Cohen's kappa 0.93 [95%CI 0.8-1.0]). Of the 66 HPV-driven OPSCC, 63 were HPV16 E6 seropositive, compared to only one (1.8%) among the 54 non-HPV-driven OPSCC, resulting in a sensitivity of 96% (95%CI 88-98) and a specificity of 98% (95%CI 90-100). Of 94 HNSCC outside the oropharynx, six (6%) were HPV16-driven. In these patients, HPV16 E6 seropositivity had lower sensitivity (50%, 95%CI 19-81), but was highly specific (100%, 95%CI 96-100). In conclusion, HPV16 E6 seropositivity appears to be a highly reliable diagnostic marker for HPV16-driven OPSCC with very high sensitivity and specificity, but might be less sensitive for HPV16-driven HNSCC outside the oropharynx.
为确定HPV16血清学作为HPV16驱动的口咽鳞状细胞癌（OPSCC）诊断标志物的敏感性和特异性，本研究纳入了214例来自德国和意大利的头颈部鳞状细胞癌（HNSCC）患者，这些患者均有新鲜冷冻的肿瘤组织以及治疗前采集的血清。120例癌症病例来自口咽，94例来自口咽以外的头颈部癌症区域（45例口腔、12例下咽和35例喉）。通过多重血清学分析了针对HPV16早期（E1、E2、E6和E7）和晚期（L1）蛋白的血清抗体，并与作为金标准的肿瘤HPV RNA状态进行了比较。当存在HPV16 DNA和HPV16转化特异性RNA转录模式（E6*I、E1 E4和E1C）时，肿瘤被定义为HPV驱动。在120例OPSCC中，66例（55%）为HPV16驱动。HPV16 E6血清阳性是HPV16驱动的OPSCC的最佳预测指标（诊断准确性97%[95%CI 92 - 99%]，Cohen's kappa 0.93[95%CI 0.8 - 1.0]）。在66例HPV驱动的OPSCC中，63例HPV16 E6血清阳性，相比之下，54例非HPV驱动的OPSCC中只有1例（1.8%）血清阳性，敏感性为96%（95%CI 88 - 98），特异性为98%（95%CI 90 - 100）。在94例口咽以外的HNSCC中，6例（6%）为HPV16驱动。在这些患者中，HPV16 E6血清阳性的敏感性较低（50%，95%CI 19 - 81），但特异性很高（100%，95%CI 96 - 100）。总之，HPV16 E6血清阳性似乎是HPV16驱动的OPSCC高度可靠的诊断标志物，具有非常高的敏感性和特异性，但对口咽以外HPV16驱动的HNSCC可能敏感性较低。
