Deng Zeyi, Uehara Takayuki, Maeda Hiroyuki, Hasegawa Masahiro, Matayoshi Sen, Kiyuna Asanori, Agena Shinya, Pan Xiaoli, Zhang Chunlin, Yamashita Yukashi, Xie Minqiang, Suzuki Mikio
Department of Otorhinolaryngology, Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China; Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
PLoS One. 2014 Nov 18;9(11):e113702. doi: 10.1371/journal.pone.0113702. eCollection 2014.
To investigate the prevalence, genotypes, and prognostic values of Epstein-Barr virus (EBV) and human papillomavirus (HPV) infections in Japanese patients with different types of head and neck cancer (HNC).
HPV and EBV DNA, EBV genotypes and LMP-1 variants, and HPV mRNA expression were detected by PCR from fresh-frozen HNC samples. HPV genotypes were determined by direct sequencing, and EBV encoded RNA (EBER) was examined by in situ hybridization.
Of the 209 HNC patients, 63 (30.1%) had HPV infection, and HPV-16 was the most common subtype (86.9%). HPV E6/E7 mRNA expression was found in 23 of 60 (38.3%) HPV DNA-positive cases detected. The site of highest prevalence of HPV was the oropharynx (45.9%). Among 146 (69.9%) HNCs in which EBV DNA was identified, 107 (73.3%) and 27 (18.5%) contained types A and B, respectively, and 124 (84.9%) showed the existence of del-LMP-1. However, only 13 (6.2%) HNCs were positive for EBER, 12 (92.3%) of which derived from the nasopharynx. Co-infection of HPV and EBER was found in only 1.0% of HNCs and 10.0% of NPCs. Kaplan-Meier survival analysis showed significantly better disease-specific and overall survival in the HPV DNA+/mRNA+ oropharyngeal squamous cell carcinoma (OPC) patients than in the other OPC patients (P = 0.027 and 0.017, respectively). Multivariate analysis showed that stage T1-3 (P = 0.002) and HPV mRNA-positive status (P = 0.061) independently predicted better disease-specific survival. No significant difference in disease-specific survival was found between the EBER-positive and -negative NPC patients (P = 0.155).
Our findings indicate that co-infection with HPV and EBV is rare in HNC. Oropharyngeal SCC with active HPV infection was related to a highly favorable outcome, while EBV status was not prognostic in the NPC cohort.
研究日本不同类型头颈癌（HNC）患者中爱泼斯坦-巴尔病毒（EBV）和人乳头瘤病毒（HPV）感染的患病率、基因型及预后价值。
通过聚合酶链反应（PCR）从新鲜冷冻的HNC样本中检测HPV和EBV DNA、EBV基因型和LMP-1变异体以及HPV mRNA表达。通过直接测序确定HPV基因型，通过原位杂交检测EBV编码RNA（EBER）。
在209例HNC患者中，63例（30.1%）存在HPV感染，其中HPV-16是最常见的亚型（86.9%）。在检测的60例HPV DNA阳性病例中，有23例（38.3%）发现HPV E6/E7 mRNA表达。HPV感染患病率最高的部位是口咽（45.9%）。在146例（69.9%）检测到EBV DNA的HNC中，分别有107例（73.3%）和27例（18.5%）含有A和B型，124例（84.9%）存在del-LMP-1。然而，只有13例（6.2%）HNC的EBER呈阳性，其中12例（92.3%）来自鼻咽。仅1.0%的HNC和10.0%的鼻咽癌（NPC）存在HPV和EBER的共同感染。Kaplan-Meier生存分析显示，HPV DNA+/mRNA+口咽鳞状细胞癌（OPC）患者的疾病特异性生存率和总生存率显著高于其他OPC患者（分别为P = 0.027和0.017）。多因素分析显示，T1-3期（P = 0.002）和HPV mRNA阳性状态（P = 0.061）独立预测更好的疾病特异性生存率。EBER阳性和阴性的NPC患者在疾病特异性生存率方面无显著差异（P = 0.155）。
我们的研究结果表明，HNC中HPV和EBV的共同感染很少见。活跃HPV感染的口咽鳞状细胞癌与非常好的预后相关，而EBV状态在NPC队列中对预后无影响。
