BACKGROUND. Multiple immunologic parameters have provided useful prognostic and assessment significance in different cancers, including head and neck squamous cell carcinoma. We sought to identify whether pre-treatment inflammatory markers could prognosticate recurrence in patients with advanced (stage III or IV) head and neck squamous cell carcinomas that underwent therapy with curative intent in a tertiary care center between January 2010 and December 2012.METHODS. We registered patient demographics, primary tumor characteristics, Human papillomavirus (HPV) status, pre-therapeutic inflammatory markers including body mass index (BMI), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), and serum albumin; therapy received, date of relapse, death or last follow up. The main outcome was relapse free survival (RFS). Overall survival (OS) was a secondary outcome.RESULTS. 235 charts were reviewed, 118 were included. Of these, 86 were oropharyngeal (50 HPV related, 18 were non-HPV related, 17 not available) and 32 non-oropharyngeal (19 HPV related, 7 non-HPV related, and 6 not available). Median follow-up was 2.45 years (IQR, 1.65-3.3). With regards to RFS, HPV positive status had an adjusted HR of 0.357 (95% CI 0.173-0.776, p=0.0087) and for NLR >=5, the raw HR was 1.637 (95% CI 0.673-3.983, p=0.2771). For OS, the raw HR for NLR >=5 was 2.997 (95% CI 1.280-7.018-, p=0.0114), and for HPV positive status, the raw HR was 0.514 (95% CI 0.226-1.169, p=0.1125). Only 54 patients had CRP available for analysis. For RFS, CRP >=8 had a raw HR of 2.350 (95% CI 1.1062-5.198, p=0.0349) and a raw HR of 1.455 (95% CI 0.497-4.260, p=0.4940) for OS. When adjusting NLR for age, gender and p16 positive status, NLR had a decreased hazard ratio of 2.352 (95% CI= 0.945-5.853, p=0.0659) for overall survival.CONCLUSIONS. NLR>=5 at presentation is not associated with a higher risk of relapse but is associated with a higher risk of death in patients with squamous cell carcinoma of the head and neck. CRP >=8 was associated with a higher risk of relapse but not death. Lastly, HPV positive status was protective with a lower risk of relapse but not death. Interestingly, we found that when adjusting NLR for age, gender and HPV positive status, NLR had a decreased hazard ratio and therefore potentially protective status for overall survival.