Relative Biological Effectiveness of Carbon Ions for Head-and-Neck Squamous Cell Carcinomas According to Human Papillomavirus Status.

Naoto Osu,Atsushi Musha,Tatsuya Ohno,Yuka Hirota,Takahiro Oike,Hiro Sato,Daijiro Kobayashi,Katsuyuki Shirai,Atsushi Shibata

doi:10.3390/jpm10030071

Abstract

Carbon-ion radiotherapy (CIRT) has strong antitumor effects and excellent dose conformity. In head-and-neck squamous cell carcinoma (HNSCC), human papillomavirus (HPV) status is a prognostic factor for photon radiotherapy outcomes. However, the effect of HPV status on the sensitivity of HNSCCs to carbon ions remains unclear. Here, we showed that the relative biological effectiveness (RBE) of carbon ions over X-rays was higher in HPV-negative cells than in HSGc-C5 cells, which are used for CIRT dose establishment, whereas the RBE in HPV-positive cells was modest. These data indicate that CIRT is more advantageous in HPV-negative than in HPV-positive HNSCCs.

Highlights

Carbon-ion radiotherapy (CIRT) is a promising modality with a strong antitumor effect even in tumors resistant to conventional photon radiotherapy [1]
We examined the carbon-ion sensitivity of head-and-neck squamous cell carcinoma (HNSCC) according to Human papillomavirus (HPV) status, as well as the relative biological effectiveness (RBE) of CIRT in this patient population
These data are consistent with the findings of previous studies showing that HPV-negative head-and-neck tumors are resistant to X-rays compared with their HPV-positive counterparts and confirm the robustness of the present experimental system for the assessment of radiosensitivity [8]

Summary

Introduction

Carbon-ion radiotherapy (CIRT) is a promising modality with a strong antitumor effect even in tumors resistant to conventional photon radiotherapy [1]. Studies suggest p53-associated apoptosis and DNA repair as candidate mechanisms [8] For the former, it is considered that the function of p53 in inducing apoptosis is retained in HPV-positive head and neck cancer cells, downregulated by the HPV E6-oncoprotein, whereas HPV-negative head and neck cancer cells harbor genetic alterations in p53, contributing to the anti-apoptotic phenotype. The effect of HPV status on the relative biological effectiveness (RBE) of carbon ions remains unclear To address these issues, we examined the carbon-ion sensitivity of HNSCCs according to HPV status, as well as the RBE of CIRT in this patient population

Methods

Results

Conclusion