Epstein-Barr virus and human papillomavirus infections and genotype distribution in head and neck cancers.

Jeffrey Chalmers,Masahiro Hasegawa,Minqiang Xie,Hiroyuki Maeda,Xiaoli Pan,Takayuki Uehara,Chunlin Zhang,Zeyi Deng,Yukashi Yamashita,Mikio Suzuki,Sen Matayoshi,Shinya Agena,Asanori Kiyuna

doi:10.1371/journal.pone.0113702

Jeffrey Chalmers, Masahiro Hasegawa + Show 11 more

Open Access

https://doi.org/10.1371/journal.pone.0113702

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Abstract

ObjectiveTo investigate the prevalence, genotypes, and prognostic values of Epstein-Barr virus (EBV) and human papillomavirus (HPV) infections in Japanese patients with different types of head and neck cancer (HNC).Methods and MaterialsHPV and EBV DNA, EBV genotypes and LMP-1 variants, and HPV mRNA expression were detected by PCR from fresh-frozen HNC samples. HPV genotypes were determined by direct sequencing, and EBV encoded RNA (EBER) was examined by in situ hybridization.ResultsOf the 209 HNC patients, 63 (30.1%) had HPV infection, and HPV-16 was the most common subtype (86.9%). HPV E6/E7 mRNA expression was found in 23 of 60 (38.3%) HPV DNA-positive cases detected. The site of highest prevalence of HPV was the oropharynx (45.9%). Among 146 (69.9%) HNCs in which EBV DNA was identified, 107 (73.3%) and 27 (18.5%) contained types A and B, respectively, and 124 (84.9%) showed the existence of del-LMP-1. However, only 13 (6.2%) HNCs were positive for EBER, 12 (92.3%) of which derived from the nasopharynx. Co-infection of HPV and EBER was found in only 1.0% of HNCs and 10.0% of NPCs. Kaplan-Meier survival analysis showed significantly better disease-specific and overall survival in the HPV DNA+/mRNA+ oropharyngeal squamous cell carcinoma (OPC) patients than in the other OPC patients (P = 0.027 and 0.017, respectively). Multivariate analysis showed that stage T1–3 (P = 0.002) and HPV mRNA-positive status (P = 0.061) independently predicted better disease-specific survival. No significant difference in disease-specific survival was found between the EBER-positive and -negative NPC patients (P = 0.155).ConclusionsOur findings indicate that co-infection with HPV and EBV is rare in HNC. Oropharyngeal SCC with active HPV infection was related to a highly favorable outcome, while EBV status was not prognostic in the NPC cohort.

Highlights

Head and neck cancer (HNC) is the sixth leading cancer in the world, with more than 600,000 new cases reported each year [1]
Our findings indicate that co-infection with Human papillomavirus (HPV) and Epstein-Barr virus (EBV) is rare in HNC
The fact that HPV is detected in non-oropharyngeal HNC suggests that its role in the development and progression of HNC is not limited to the oropharynx [5], but includes the nasopharynx, where Epstein-Barr virus (EBV) is consistently detected in cancer cells from regions of high and low incidence [6]

Summary

Introduction

Head and neck cancer (HNC) is the sixth leading cancer in the world, with more than 600,000 new cases reported each year [1]. Excessive alcohol and tobacco consumption are two traditional and major risk factors for HNC. In the last two decades, the incidence of HNC, such as carcinoma of the larynx or hypopharynx, has decreased significantly due to preventive strategies targeting these risk factors. The incidence of oropharyngeal squamous cell carcinoma (OPC) has increased sharply, in young-onset HNC in the absence of these traditional risk factors, which suggests the involvement of other factors. The fact that HPV is detected in non-oropharyngeal HNC suggests that its role in the development and progression of HNC is not limited to the oropharynx [5], but includes the nasopharynx, where Epstein-Barr virus (EBV) is consistently detected in cancer cells from regions of high and low incidence [6]

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Results

Conclusion