title: HPV Status Determines the Efficacy of Adjuvant Chemotherapy With S-1, an Oral Fluorouracil Prodrug, in Oropharyngeal Cancer.
abstract: OBJECTIVE
  A subgroup of oropharyngeal squamous cell carcinoma (OPC) is infected with high-risk human papillomavirus (HPV). The object of this study is to evaluate the efficacy of adjuvant chemotherapy with S-1, an oral 5-fluorouracil prodrug, on survival of patients with OPC according to HPV status.
  
  
  METHODS
  Among OPC patients of stage III or IV who received definitive treatment from 1998 to 2008, 38 who were confirmed tumor-free after primary treatment were analyzed. Before 2003, none of the patients received S-1 adjuvant chemotherapy (S-1(-)-group); however, all patients who were eligible were administered S-1 (S-1(+)-group) after 2003. The expression of thymidylate synthase (TYMS) involved in 5-FU metabolism was also examined in protein and mRNA levels.
  
  
  RESULTS
  Although there was a trend to disease-free and overall survival benefit in HPV-negative patients with S-1, it did not achieve statistical significance (P=.082 and P=.065, respectively). For the HPV-positive patients, the survivals were similar with or without S-1 administration. TYMS-expression in HPV-positive OPC tissues was significantly higher than in HPV-negative ones in both protein and mRNA levels (P=.0489 and P=.0446, respectively).
  
  
  CONCLUSIONS
  The current study provides a rationale to plan a randomized trial to compare the efficacy of S-1 according to the HPV status in OPCs.
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Wakisaka
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kondo
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Kita
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
authors.forename: Kazuhira
authors.initials: K
authors.lastname: Endo
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tsuji
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Murono
authors.affiliation: Division of Molecular Genetics, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Muramatsu
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan tomoy@med.kanazawa-u.ac.jp.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Yoshizaki
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009959:Oropharyngeal Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000821:virology*; D010094:Oxonic Acid / Q000627:therapeutic use*; D027383:Papillomaviridae / Q000235:genetics*; D011355:Prodrugs; D012189:Retrospective Studies; D005641:Tegafur / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011355:Prodrugs; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D005472:Fluorouracil
keywords: 5-fluorouracil; S-1 adjuvant chemotherapy; human papillomavirus; oropharyngeal squamous cell carcinoma; thymidylate synthase