Human papillomavirus and p53 mutations in head and neck squamous cell carcinoma among Japanese population

Abstract

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.

Relationship Between p16 Expression and Prognosis in Patients with Oropharyngeal Cancer Undergoing Surgery

“…Thus, in this study, experienced pathologists in our hospital defined patients with the immune-positive cell ratio of 25% or more in tumor cells as having p16 positivity, according to previous report (15). In this study, the p16-positive rate was 43.75%, which is in line with previous data (9,20,(22)(23)(24)(25).…”

Prevalence, Clinicopathological Characteristics, and Outcome of Human Papillomavirus–Associated Oropharyngeal Cancer in Southern Chinese Patients

“…In contrast with the West, there has been relatively little interest from Asian nations on this newly recognized disease. In Asia, the reported prevalence of HPV in oropharyngeal cancer ranges from 0% to 34.4% (9)(10)(11)(12). Similar to those reported from Europe and North America, a recent multicenter study from Korea showed an increase in the proportion of tonsillar SCC due to HPV from 5.9% in 1991 to 31.6% in 2009 (13,14).…”

High-Risk Human Papillomavirus in Oral Cancer: Clinical Implications

“…Inactivating p53 mutations are rarely seen in HPV-positive tumours (7.1%) compared with HPV-negative tumours (48.3%), with inactivation of p53 achieved by the HPV E6 protein [27]. Degradation of the p53 protein results due to the binding of E6 to E3 ubiquitin ligases leading to cell cycle deregulation, due to loss of p21 function and loss of p53-mediated apoptosis [27,28]. Additionally, E6 interacts with pro-apoptotic proteins Bak and procaspase 8 to prevent apoptosis and activates telomerase associated with cell immortalization [29,30] (Fig.…”

“…The oncogenic E6 and E7 of HR-HPV16/18 inactivate critical tumour suppressor genes, p53 and pRb. Inactivating p53 mutations are rarely seen in HPV-positive tumours (7.1%) compared with HPV-negative tumours (48.3%), with inactivation of p53 achieved by the HPV E6 protein [27]. Degradation of the p53 protein results due to the binding of E6 to E3 ubiquitin ligases leading to cell cycle deregulation, due to loss of p21 function and loss of p53-mediated apoptosis [27,28].…”