Impact of cisplatin dose intensity on human papillomavirus-related and -unrelated locally advanced head and neck squamous cell carcinoma

Anna Spreafico, Shao Hui Huang, Wei Xu, Roberta Granata, Chen Shin Liu, John N. Waldron, Eric Chen, Jolie Ringash, Andrew Bayley, Kelvin K W Chan, Andrew J. Hope, John Cho, Albiruni A R Razak, Aaron Hansen, Raymond Jang, Bayardo Perez-Ordonez, Ilan Weinreb, Paolo Bossi, Ester Orlandi, Lisa F. LicitraYuyao Song, Brian O'Sullivan, Lillian L. Siu, John Kim

Research output: Contribution to journalArticlepeer-review


Aim The aim is to evaluate the impact of cisplatin dose modification on outcomes of human papillomavirus (HPV)-related (HPV+) and HPV-unrelated (HPV−) locally advanced head and neck cancer (LAHNC) treated with chemoradiotherapy (CRT). Patients and methods A pooled analysis was conducted of stage III/IV oropharyngeal cancer (OPC), carcinoma of unknown primary (CUP) and laryngo-hypopharyngeal cancer (LHC) patients treated with single-agent cisplatin CRT in 2000–2012 from two tertiary academic cancer centres. HPV status was determined by p16 staining and/or in situ hybridisation. LHC was assumed to be HPV−. Unknown HPV status OPC/CUPs were excluded. Overall survival (OS) was calculated. Multivariable analysis (MVA) evaluated the impact of cisplatin dose intensity on survival for HPV+ and HPV− cohorts separately. Results A total of 404 HPV+ and 255 HPV− LAHNC (481 OPC, 18 CUP, 160 LHC) patients were included. Median follow-up was 4.3 (0.5–11.9) years. Three-year OS for cisplatin <200, =200, and >200 mg/m2 subgroups were 52%, 60%, and 72% (P = 0.001) for the HPV− and 91%, 90%, and 91% (P = 0.30) for the HPV+ patients. MVA confirmed a survival benefit with cisplatin >200 mg/m2 for the HPV− (hazard ratio [HR] 0.5, 95% confidence interval [CI]: 0.3–0.7, P < 0.001) but not for HPV+ (HR 0.6, 95% CI: 0.4–1.1, P = 0.104). There was a superior OS trend in the HPV+ T4 or N3 high-risk subset (N = 107) with cisplatin >200 mg/m2 (HR 0.5, 95% CI: 0.2–1.1, P = 0.07). Conclusions A survival benefit of cisplatin dose >200 mg/m2 is evident for HPV− LAHNC patients, but not for HPV+ cohort overall, although the T4 or N3 subset may benefit from a higher cumulative cisplatin dose.

Original languageEnglish
Pages (from-to)174-182
Number of pages9
JournalEuropean Journal of Cancer
Publication statusPublished - Nov 1 2016


  • Chemoradiotherapy
  • Cisplatin
  • Head and neck cancer
  • Human papillomavirus
  • Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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