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

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.