Department of Otorhinolaryngology - Head and Neck Surgery, Osaka University Faculty of Medicine, Suita, Japan.
Cancer Sci. 2014 Apr;105(4):409-17. doi: 10.1111/cas.12369. Epub 2014 Mar 30.
We aimed to reveal the prevalence and pattern of human papillomavirus (HPV) infection and p53 mutations among Japanese head and neck squamous cell carcinoma (HNSCC) patients in relation to clinicopathological parameters. Human papillomavirus DNA and p53 mutations were examined in 493 HNSCCs and its subset of 283 HNSCCs. Oropharyngeal carcinoma was more frequently HPV-positive than non-oropharyngeal carcinoma (34.4% vs 3.6%, P < 0.001), and HPV16 accounted for 91.1% of HPV-positive tumors. In oropharyngeal carcinoma, which showed an increasing trend of HPV prevalence over time (P < 0.001), HPV infection was inversely correlated with tobacco smoking, alcohol drinking, p53 mutations, and a disruptive mutation (P = 0.003, <0.001, <0.001, and <0.001, respectively). The prevalence of p53 mutations differed significantly between virus-unrelated HNSCC and virus-related HNSCC consisting of nasopharyngeal and HPV-positive oropharyngeal carcinomas (48.3% vs 7.1%, P < 0.001). Although p53 mutations were associated with tobacco smoking and alcohol drinking, this association disappeared in virus-unrelated HNSCC. A disruptive mutation was never found in virus-related HNSCC, whereas it was independently associated with primary site, such as the oropharynx and hypopharynx (P = 0.01 and 0.03, respectively), in virus-unrelated HNSCC. Moreover, in virus-unrelated HNSCC, G:C to T:A transversions were more frequent in ever-smokers than in never-smokers (P = 0.04), whereas G:C to A:T transitions at CpG sites were less frequent in ever-smokers than in never-smokers (P = 0.04). In conclusion, HNSCC is etiologically classified into virus-related and virus-unrelated subgroups. In virus-related HNSCC, p53 mutations are uncommon with the absence of a disruptive mutation, whereas in virus-unrelated HNSCC, p53 mutations are common, and disruptive mutagenesis of p53 is related with oropharyngeal and hypopharyngeal carcinoma.
我们旨在揭示 HPV 感染和 p53 突变在日本头颈部鳞状细胞癌（HNSCC）患者中的流行率和模式，以及它们与临床病理参数的关系。我们检测了 493 例 HNSCC 及其 283 例 HNSCC 亚组的 HPV DNA 和 p53 突变。口咽癌 HPV 阳性率明显高于非口咽癌（34.4% vs. 3.6%，P<0.001），HPV16 占 HPV 阳性肿瘤的 91.1%。在口咽癌中，HPV 感染呈随时间增加的趋势（P<0.001），与吸烟、饮酒、p53 突变和破坏性突变呈负相关（P=0.003、<0.001、<0.001 和<0.001）。病毒无关型 HNSCC 和包括鼻咽癌和 HPV 阳性口咽癌的病毒相关型 HNSCC 之间的 p53 突变率有显著差异（48.3% vs. 7.1%，P<0.001）。尽管 p53 突变与吸烟和饮酒有关，但在病毒无关型 HNSCC 中这种关联消失了。破坏性突变从未在病毒相关型 HNSCC 中发现，而它与原发部位如口咽和下咽独立相关（P=0.01 和 0.03），在病毒无关型 HNSCC 中。此外，在病毒无关型 HNSCC 中，吸烟者 G:C 到 T:A 颠换的频率高于不吸烟者（P=0.04），而 CpG 位点 G:C 到 A:T 的转换频率在吸烟者中低于不吸烟者（P=0.04）。总之，HNSCC 可以分为病毒相关型和病毒无关型。在病毒相关型 HNSCC 中，p53 突变不常见且无破坏性突变，而在病毒无关型 HNSCC 中，p53 突变常见，p53 的破坏性突变与口咽和下咽癌相关。
