Intrinsic Radiosensitivity Is Not the Determining Factor in Treatment Response Differences between HPV Negative and HPV Positive Head and Neck Cancers.

Paul Reid,Ian Olver,Loredana G Marcu,Alexander H Staudacher,Leyla Moghaddasi,Michael P Brown,Eva Bezak,Yanrui Li

doi:10.3390/cells9081788

Abstract

Head and neck squamous cell carcinomas (HNSCC) resulting from human papillomavirus (HPV) are increasing in incidence but demonstrate significantly better treatment response than HNSCC from other causes such as tobacco and alcohol. This study sought to identify differences in HNSCC, intrinsic to HPV status, in their response to radiation dose. Previously unexamined changes in radio-responsiveness following fractionated X-ray irradiation were compared between HPV positive and negative statuses of HNSCC. Six HNSCC cell lines, 3 of each HPV status, were investigated for radiosensitivity by clonogenic assay and modelled by response as a function of dose. Generational cultures of each cell line were developed to follow changes in radiosensitivity after repeated irradiations simulating fractionated radiation therapy. As a group, the HPV positive cell lines were more radiosensitive, but with changes following repeated fractions of dose, and modelling of response as a function of dose, both statuses displayed large radiobiological heterogeneity. These findings challenge current radiobiological assumptions of head and neck cancers as early responding tissue to radiation and may go some way in explaining difficulties reaching consensus in stratification of treatment by HPV status. Consequently, results from this study do not support stratifying radiation therapy by HPV status.

Highlights

Head and neck cancers are heterogeneous, occurring from the oral and nasal cavities to the larynx and pharyngeal areas where about 95% are squamous cell carcinomas (HNSCC) of the mucosalCells 2020, 9, 1788; doi:10.3390/cells9081788 www.mdpi.com/journal/cellsCells 2020, 9, 1788 epithelium [1]
The most significant differences in radiosensitivity among cell line groups defined by human papillomavirus (HPV) status was at 1.0 and 2.0 Gy absorbed dose
All cell lines displayed increasing radiosensitivity with repeated 4 Gy radiation dose fractions except the 2nd generations of UM-SCC-17a and UM-SCC-22a which showed a transient increase in radioresistance

Summary

Introduction

Head and neck cancers are heterogeneous, occurring from the oral and nasal cavities to the larynx and pharyngeal areas where about 95% are squamous cell carcinomas (HNSCC) of the mucosalCells 2020, 9, 1788; doi:10.3390/cells9081788 www.mdpi.com/journal/cellsCells 2020, 9, 1788 epithelium [1]. Head and neck cancers are heterogeneous, occurring from the oral and nasal cavities to the larynx and pharyngeal areas where about 95% are squamous cell carcinomas (HNSCC) of the mucosal. Causes of head and neck cancers fall into 2 main etiological groups, being. Oropharyngeal squamous cell carcinoma (OPSCC) represents a growing subset of HNSCC due to the increasing incidence of HPV driven tumors, and the preference shown by HPV for this anatomical area [3,4]. Diagnosis of HPV positive HNSCC is typically in a younger demographic and its rise in incidence has overtaken HPV associated cervical cancers, stressing the growing health concern and emphasis on research efforts to understand the best approaches to the control of the 2 etiological groups [5]. Moves to use HPV status as a marker for treatment stratification require a more predictive understanding of response to radiation dose in terms of HPV status

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