The impact of Human Papilloma Virus status on the prediction of head and neck cancer chemoradiotherapy outcomes using the pre-treatment apparent diffusion coefficient

Abstract

Objective: To determine the impact of Human Papilloma Virus (HPV) oropharyngeal cancer (OPC) status on the prediction of head and neck squamous cell cancer (HNSCC) chemoradiotherapy (CRT) outcomes with pre-treatment quantitative diffusion-weighted magnetic resonance imaging (DW-MRI).

Methods: Following ethical approval, 65 participants (53 male, age 59.9 ± 7.86) underwent pre-treatment DW-MRI in this prospective cohort observational study. There were 46 HPV OPC and 19 other HNSCC cases with Stage III/IV HNSCC. Regions of interest (ROIs) (volume, largest area, core) at the primary tumour (n = 57) and largest pathological node (n = 59) were placed to analyse ADC_mean and ADC_min. Unpaired t-test or Mann-Whitney test evaluated the impact of HPV OPC status and clinical parameters on their prediction of post-CRT 2 year locoregional and disease-free survival (LRFS and DFS). Multivariate logistic regression compared significant variables with 2 year outcomes.

Results: On univariate analysis of all participants, the primary tumour area ADC_mean was predictive of 2 year LRFS (p = 0.04). However, only the HPV OPC diagnosis (LFRS p = 0.03; DFS p = 0.02) predicted outcomes on multivariate analysis. None of the pre-treatment ADC values were predictive of 2 year DFS in the HPV OPC subgroup (p = 0.21-0.68). Amongst participants without 2 year disease-free survival, HPV-OPC was found to have much lower primary tumour ADC_mean values than other HNSCC.

Conclusion: Knowledge of HPV OPC status is required in order to determine the impact of the pre-treatment ADC values on post-CRT outcomes in HNSCC.

Advances in knowledge: Pre-treatment ADC_mean and ADC_min values acquired using different ROI methods are not predictive of 2 year survival outcomes in HPV OPC.

Figure 1.

A HPV positive oropharyngeal cancer patient with a largely cystic right level two lymph node. (a) T₁W post-gadolinium axial image b) b = 0 s/mm² map from DW-MRI c) b = 800 s/mm² map from DW-MRI indicating aROI as the whole of the lymph node outline and d) b = 800 s/mm² map from DW-MRI indicating rROI as the component of the lesion returning intermediate signal on the b = 0 map and with enhancement on the T₁W post gadolinium axial image. DW-MRI, diffusion-weighted MRI; HPV, human papilloma virus; ROI, region of interest.

Figure 2.

A HPV negative oropharyngeal cancer patient with a left palatine tonsillar cancer and left level two necrotic lymph node. (a) T1w post gadolinium axial image demonstrates the left palatine tonsillar tumour and the left level two lymph node (arrows). (b) b = 800 s/mm² map from DW-MRI indicating aROIs as the continuous bold lines and rROIs as the dotted lines. DW-MRI, diffusion-weighted MRI; HPV, human papilloma virus; ROI, region of interest.

Figure 3.

Participant flow chart.

Figure 4.

Primary tumour aROI ADC (10⁻⁶ mm²/s) in patients with and without 2 year LRFS. ADC< apparent diffusion coefficient; LRFS, locoregional and disease-free survival; ROI, region of interest.