title: Epstein-Barr virus and human papillomavirus infections and genotype distribution in head and neck cancers.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Zeyi
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Uehara
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Maeda
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hasegawa
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Sen
authors.initials: S
authors.lastname: Matayoshi
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Asanori
authors.initials: A
authors.lastname: Kiyuna
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Agena
authors.affiliation: 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.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Pan
authors.affiliation: 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.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Yukashi
authors.initials: Y
authors.lastname: Yamashita
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Minqiang
authors.initials: M
authors.lastname: Xie
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Suzuki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060085:Coinfection / Q000453:epidemiology / Q000821:virology; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000453:epidemiology / Q000821:virology*; D005260:Female; D015967:Gene Expression Regulation, Viral; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000453:epidemiology / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D007564:Japan / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics / Q000502:physiology*; D050725:Papillomavirus E7 Proteins / Q000235:genetics; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000821:virology*; D015995:Prevalence; D011446:Prospective Studies; D012367:RNA, Viral / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; C099537:Epstein-Barr virus encoded RNA 1; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012367:RNA, Viral; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16