Abstract

Shao Hui Huang, John Waldron, Xiaowei Shen, Michael Milosevic,  Jolie Ringash, Li Tong, Andrew Bayley, John Kim, Andrew Hope, John Cho, Meredith Giuliani, Fei-Fei Liu, Wei Xu, Brian O’Sullivan
Princess Margaret Cancer Centre, University of Toronto, Toronto, ON

Purpose: To investigate the prognostic value of pre-radiotherapy/chemoradiotherapy (RT/CRT) circulating neutrophil counts (CNC) in HPV-related [HPV(+)] and unrelated [HPV(-)] oropharyngeal cancer (OPC).

Materials and Methods: All OPC treated with RT/CRT from 2000-2010 were included. HPV status was ascertained by p16 staining. Based on median value of CNC, patients were dichotomized into low versus high CNC cohorts for HPV(+) and HPV(-) OPC separately. Actuarial rates of overall survival (OS), loco-regional control (LRC), and distant control (DC) were compared between high versus low CNC cohorts. Multivariate analysis (MVA) was applied to confirm the prognostic value of CNC (as a continuous variable) for OS, LRC and DC.

Results: A total of 702 OPC [510 HPV(+) and 192 HPV(-)] cases were included. Median follow-up was 5.1 and 4.1 years for the HPV(+) and HPV(-) OPC respectively. Median CNC [higher for the HPV(-) versus HPV(+) cases (5.5 versus 4.7 x109/L, p<0.001)] divided the HPV(-) into 96 high and 96 low CNC and the HPV(+) into 263 high versus 247 low cohorts. Irrespective of HPV status, the high CNC group comprised significantly more current smokers [HPV(+): 39 versus 22%, p<0.001; HPV(-): 74 versus 60%, p=0.046] and N3 disease [HPV(+): 13 versus 5%, p=0.002; HPV(-): 15 versus 1%, p<0.001]. T4 tumours were also observed more frequently in the HPV(+) high versus low CNC group (24 versus 14%, p<0.001) but was similar for the HPV(-) OPC (35 versus 30%, p=0.473). The high CNC cohort had reduced three-year OS [HPV(+): 77 versus 85%, p<0.001; HPV(-): 37 versus 55%, p=0.008], LRC [HPV(+): 83 versus 93%, p=0.001; HPV(-): 67 versus 78%, p=0.050], and DC [HPV(+): 85 versus 90%, p=0.034; HPV(-): 75 versus 91%, p=0.009] compared to the low CNC. MVA (adjusting for age, smoking pack-years, T-, N-, and treatment) confirmed that each 109/L increment in CNC count was strongly predictive for more deaths (HR=1.2, p=0.02), locoregional failure (HR=1.1, p=0.02), and distant metastasis (HR=1.2, p<0.01) for the HPV(+) but was non-significant for the HPV(-) [death: HR 1.05, p=0.22; recurrence: HR 1.04, p=0.41)]. The prognostic value of CNC for OS and recurrences in HPV(+) OPC was further confirmed in CRT (n=264) and RT-alone (n=246) subgroups, and in non-smokers (n=188) subset (HR 1.2-1.3, all p<0.01) in MVA.

Conclusions: In this relatively large cohort, we identify that HPV(+) OPC patients with higher CNC have inferior survival and increased risk of loco-regional, and distant metastasis, independent of smoking status or treatment modality. This association was not apparent in HPV(-) patients. The results suggest a differential tumour activity associated with high CNC in the HPV(+) OPC. Further study is needed to understand the biology of this observation and to potentially identify new therapeutic targets.