Huang Chung-Guei, Lee Li-Ang, Liao Chun-Ta, Yen Tzu-Chen, Yang Shu-Li, Liu Yi-Chun, Li Jung-Chin, Gong Yu-Nong, Kang Chung-Jan, Huang Shiang-Fu, Fang Ku-Hao, Chang Kai-Ping, Lee Li-Yu, Hsueh Chuen, Shih Shin-Ru, Tsao Kuo-Chien
Department of Laboratory Medicine, Head and Neck Oncology Group, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan, ROC.
Oncotarget. 2017 May 23;8(21):34820-34835. doi: 10.18632/oncotarget.16747.
Human papillomavirus (HPV) infections predict mortality in Taiwanese patients with oral cavity squamous cell carcinoma (OCSCC). To address their prognostic significance for local recurrence (LR), in this retrospective cohort study we investigated different serologic and molecular markers of HPV 16 infection in 85 consecutive patients with primary OCSCC who received standard treatment and had their sera stored before treatment. Resected tumor specimens were examined with PCR-based assays for HPV 16 E6/E7 mRNA expression. Sera were tested with suspension arrays for the presence of HPV-specific antibodies using synthetic L1 and E6 peptides as well as a synthetic E7 protein. HPV 16 E6/E7 mRNA, anti-L1, anti-E6, and anti-E7 antibodies tested positive in 12%, 25%, 38%, and 41% of the study patients, respectively. Multivariate analysis identified pathological T3/T4, E6/E7 mRNA, and anti-E7 antibodies as independent risk factors for LR, whereas anti-E6 antibodies were an independent protective factor. In patients with ≥ 3 (high-risk group), 2 (intermediate-risk), and ≤ 1 (low-risk) independent risk factors (predictors), the 5-year LR rates were 75%, 42%, and 4%, respectively. Results were validated in an independent cohort. Together, our preliminary data indicate that HPV 16 infections as well as low and high serum levels of anti-E6 and anti-E7 antibodies, respectively, can serve as biomarkers of LR in patients with OCSCC, whereas the clinical usefulness of anti-HPV 16 antibodies for risk stratification of newly diagnosed cases deserves further scrutiny.
人乳头瘤病毒（HPV）感染可预测台湾口腔鳞状细胞癌（OCSCC）患者的死亡率。为了探讨其对局部复发（LR）的预后意义，在这项回顾性队列研究中，我们调查了85例接受标准治疗且治疗前血清已保存的原发性OCSCC连续患者中HPV 16感染的不同血清学和分子标志物。对切除的肿瘤标本进行基于PCR的检测，以检测HPV 16 E6/E7 mRNA表达。使用合成L1和E6肽以及合成E7蛋白，通过悬浮阵列检测血清中HPV特异性抗体的存在。研究患者中HPV 16 E6/E7 mRNA、抗L1、抗E6和抗E7抗体检测阳性率分别为12%、25%、38%和41%。多变量分析确定病理T3/T4、E6/E7 mRNA和抗E7抗体为LR的独立危险因素，而抗E6抗体为独立保护因素。在具有≥3个（高危组）、2个（中危组）和≤1个（低危组）独立危险因素（预测指标）的患者中，5年LR率分别为75%、42%和4%。结果在一个独立队列中得到验证。总之，我们的初步数据表明，HPV 16感染以及抗E6和抗E7抗体的低血清水平和高血清水平分别可作为OCSCC患者LR的生物标志物，而抗HPV 16抗体对新诊断病例进行风险分层的临床实用性值得进一步研究。
