Oton-Gonzalez Lucia, Rotondo John Charles, Lanzillotti Carmen, Mazzoni Elisa, Bononi Ilaria, Iaquinta Maria Rosa, Cerritelli Luca, Malagutti Nicola, Ciorba Andrea, Bianchini Chiara, Pelucchi Stefano, Tognon Mauro, Martini Fernanda
Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy.
Department of Translational Medicine and for Romagna, University of Ferrara, 44121 Ferrara, Italy.
Cancers (Basel). 2021 Jul 5;13(13):3370. doi: 10.3390/cancers13133370.
Despite improved prognosis for many HPV-positive head and neck squamous cell carcinomas (HNSCCs), some cases are still marked by recurrence and metastasis. Our study aimed to identify novel biomarkers for patient stratification. Classical HPV markers: HPV-DNA, p16 and HPV mRNA expression were studied in HNSCC ( = 67) and controls ( = 58) by qPCR. Subsequently, ELISA tests were used for HPV16 L1 antibody and HPV16 E7 oncoprotein detection in serum at diagnosis and follow-up. All markers were correlated to relapse-free survival (RFS) and overall survival (OS). HPV-DNA was found in HNSCCs (29.85%), HPV16-DNA in 95% of cases, HPV16 E7 mRNA was revealed in 93.75%. p16 was overexpressed in 75% of HPV-positive HNSCC compared to negative samples and controls ( < 0.001). Classical markers correlated with improved OS ( < 0.05). Serological studies showed similar proportions of HPV16 L1 antibodies in all HNSCCs ( > 0.05). Serum E7 oncoprotein was present in 30% HPV-positive patients at diagnosis ( > 0.05) and correlated to HNSCC HPV16 E7 mRNA ( < 0.01), whereas it was associated to worse RFS and OS, especially for oropharyngeal squamous cell carcinoma (OPSCC) ( < 0.01). Detection of circulating HPV16 E7 oncoprotein at diagnosis may be useful for stratifying and monitoring HPV-positive HNSCC patients for worse prognosis, providing clinicians a tool for selecting patients for treatment de-escalation.
尽管许多人乳头瘤病毒（HPV）阳性的头颈部鳞状细胞癌（HNSCC）患者的预后有所改善，但仍有一些病例以复发和转移为特征。我们的研究旨在确定用于患者分层的新型生物标志物。通过定量聚合酶链反应（qPCR）在67例HNSCC患者和58例对照中研究了经典的HPV标志物：HPV-DNA、p16和HPV mRNA表达。随后，采用酶联免疫吸附测定（ELISA）试验检测诊断和随访时血清中的HPV16 L1抗体和HPV16 E7癌蛋白。所有标志物均与无复发生存期（RFS）和总生存期（OS）相关。在HNSCC患者中发现HPV-DNA的比例为29.85%，95%的病例中发现HPV16-DNA，93.75%的病例中检测到HPV16 E7 mRNA。与阴性样本和对照相比，75%的HPV阳性HNSCC中p16过表达（P<0.001）。经典标志物与改善的OS相关（P<0.05）。血清学研究显示，所有HNSCC中HPV16 L1抗体的比例相似（P>0.05）。30%的HPV阳性患者在诊断时血清中存在E7癌蛋白（P>0.05），且与HNSCC的HPV16 E7 mRNA相关（P<0.01），而它与较差的RFS和OS相关，尤其是口咽鳞状细胞癌（OPSCC）（P<0.01）。诊断时检测循环中的HPV16 E7癌蛋白可能有助于对HPV阳性HNSCC患者进行分层和监测，以判断预后较差的情况，为临床医生提供一种选择患者进行降阶梯治疗的工具。
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