Human Papilloma Virus Associated Oropharyngeal Squamous Cell Carcinoma: Genetic Aberrations Associated with Local and Distant Recurrence

Abstract

Introduction HPV driven OPSCC proffers a more favourable prognosis in contrast to its HPV negative counterparts. Consequently, studies have analysed de-intensification measures of current treatment practices to minimise the associated morbidity. However, 25% of patients with HPV positive OPSCC experience a locoregional recurrence (LR) and/or distant metastasis (DM). The aim of this study was to identify upfront factors associated with a recurrence risk.

Materials and Methods A 10-year cohort of HPV positive OPSCC patient demographics was analysed from 3 Dublin Hospitals. In addition, HPV genotyping via Ion Torrent Next Generation Sequencing (NGS) and mutations analysis using smMIP panel based NGS was conducted on the cohort archival tumour DNA.

Results From 67 patients identified, a statistically significant correlation was identified linking excessive alcohol consumption and a higher clinical stage with LR and/or DM (P=0.033, P=0.01). Furthermore, a strong correlation was identified between lower age at diagnosis, with the development of LR and/or DM (P=0.057). HPV 16 was the most prevalent genotype (93.65%), with dual HPV infection illustrated in 4 cases. BRAF, EGFR, ERBB2, KIT, KRAS, NRAS, PDGFRA somatic mutations were not identified in the recurrence cohort.

Conclusion With the ongoing focus to reduce treatment for patient with HPV positive OPSCC, upfront recognition of patients at greater risk of LR and/or DM is essential. In the era of personalised medicine, it is hoped that interrogation of archival tumour tissue via similar techniques used in this study may yield pioneering findings with a clinical and prognostic significance.