HPV Status Determines the Efficacy of Adjuvant Chemotherapy With S-1, an Oral Fluorouracil Prodrug, in Oropharyngeal Cancer

Ann Otol Rhinol Laryngol. 2015 May;124(5):400-6. doi: 10.1177/0003489414560434. Epub 2014 Nov 25.

Abstract

Objectives: 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).

Conclusion: 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.

Keywords: 5-fluorouracil; S-1 adjuvant chemotherapy; human papillomavirus; oropharyngeal squamous cell carcinoma; thymidylate synthase.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Antimetabolites, Antineoplastic / therapeutic use
  • Chemotherapy, Adjuvant
  • Drug Combinations
  • Drug Therapy, Combination
  • Female
  • Fluorouracil / administration & dosage*
  • Humans
  • Immunohistochemistry
  • Male
  • Oropharyngeal Neoplasms / diagnosis
  • Oropharyngeal Neoplasms / drug therapy
  • Oropharyngeal Neoplasms / virology*
  • Oxonic Acid / therapeutic use*
  • Papillomaviridae / genetics*
  • Prodrugs*
  • Retrospective Studies
  • Tegafur / therapeutic use*
  • Treatment Outcome

Substances

  • Antimetabolites, Antineoplastic
  • Drug Combinations
  • Prodrugs
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Fluorouracil