title: Detection of human papillomavirus infection in oral squamous cell carcinoma: a cohort study of Japanese patients.
abstract: OBJECTIVE
  Recent evidence suggests that human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is a separate HNSCC subgroup with distinct epidemiology, histopathological characteristics, therapeutic response to chemotherapy and radiation, and clinical outcome. This study aimed to investigate the role of HPV infection in oral squamous cell carcinoma (OSCC) and the correlation between HPV infection, tumor suppressor protein p16 expression, and clinicopathological features in Japanese patients.
  
  
  METHODS
  In total, 174 OSCC specimens were examined for p16 levels by immunohistochemistry, and p16-positive OSCCs were analyzed for HPV DNA by in situ hybridization (ISH) and HPV genotypes by real-time PCR. The results were evaluated for the association with clinicopathological characteristics of OSCC patients.
  
  
  RESULTS
  Twenty-four OSCC samples were found positive for p16 expression; all of them were well-differentiated tumors. P16 immunoreactivity was significantly associated with the invasion depth and tended to correlate with sex, site in the oral cavity, stromal reaction, TNM stage, and survival. HPV DNA was detected in 13 of 24 (54%) p16-positive OSCC by real-time PCR; HPV 16, 18, and other high-risk genotypes were the most prevalent. However, ISH failed to detect HPV DNA in p16-positive OSCCs.
  
  
  CONCLUSIONS
  P16 immunoreactivity and HPV genotyping by real-time PCR may be useful markers of HPV infection in OSCC. However, although HPV-related OSCC showed good outcomes, HPV infection may have a minor role in oral oncogenesis in Japanese patients.
authors.affiliation: Division of Oral and Maxillofacial Surgery, Department of Oral Medicine and Surgery, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan.
authors.forename: Atsumu
authors.initials: A
authors.lastname: Kouketsu
authors.affiliation: Division of Pathology, Miyagi Cancer Center, Natori, Miyagi, Japan.
authors.forename: Ikuro
authors.initials: I
authors.lastname: Sato
authors.affiliation: Division of Oral and Maxillofacial Surgery, Department of Oral Medicine and Surgery, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Abe
authors.affiliation: Division of Oral Pathology, Department of Oral Medicine and Surgery, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Oikawa
authors.affiliation: Division of Oral Pathology, Department of Oral Medicine and Surgery, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan.
authors.forename: Yoshinaka
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: Division of Oral and Maxillofacial Surgery, Department of Oral Medicine and Surgery, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Division of Oral Pathology, Department of Oral Medicine and Surgery, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kumamoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000821:virology*; D015331:Cohort Studies; D004279:DNA, Viral / Q000302:isolation & purification; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology* / Q000821:virology*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000473:pathology* / Q000821:virology*; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000473:pathology* / Q000821:virology*; D015995:Prevalence; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D004279:DNA, Viral
keywords: human papillomavirus; oral cancer; p16; squamous cell carcinoma