EGFR mutations and human papillomavirus in squamous cell carcinoma of tongue and tonsil

doi:10.1016/j.ejca.2006.09.025

European Journal of Cancer

Volume 43, Issue 3, February 2007, Pages 520-526

https://doi.org/10.1016/j.ejca.2006.09.025 Get rights and content

Abstract

This study was performed to determine the clinical significance of mutations in the EGFR (epidermal growth factor receptor) along with their association with human papillomavirus (HPV) infections in patients with squamous cell carcinoma of the head and neck (HNSCC). Exons 18–21 of the EGFR tyrosine kinase domain were sequenced and HPV typing was carried out using the HPV DNA chip in tissues obtained from patients with tongue and tonsil cancer. Univariate and multivariate analyses were used to identify the significant factors. One hundred and eight patients were enrolled. Ten patients (9%) were HPV positive and 17 (16%) had EGFR mutations. None of the patients with EGFR mutations were HPV positive. Gender, age (<60 years versus ⩾60 years), and smoking history were not associated with EGFR mutations. A higher percentage of patients with tonsillar cancer were HPV positive than those with tongue cancer (26% and 0%, respectively; P < 0.001). EGFR mutations were not a significant prognostic factor (P = 0.746). HPV-positive patients had prolonged survival (P = 0.025). Multivariate analysis revealed a longer overall survival in HPV-positive patients (P = 0.007). EGFR mutations are not associated with the HPV-positive status, which may confer a better survival outcome. Clinical features of lung cancer patients with EGFR mutations were not observed in HNSCC. A further study will be needed to confirm these results.

Introduction

Squamous cell carcinoma of the head and neck (HNSCC) is the eighth most common cause of cancer death worldwide.¹ Smoking and alcohol consumption are well-established risk factors. However, a small portion of patients with head and neck cancer are nonsmokers and nondrinkers.2, 3 Recent studies have suggested that a human papillomavirus (HPV) infection is a risk factor for HNSCC.⁴ In addition, some authors have reported that an association between a HPV infection and nonsmokers.⁵ The association between a HPV infection and a carcinoma of the head and neck varies according to the anatomical site of the primary tumour. Previous studies have shown a strong association between tonsil cancer and a HPV infection.4, 5, 6, 7

Some investigators have reported EGFR mutations in a subset of patients with non-small-cell lung cancer (NSCLC).8, 9 Among several factors, never smoking was associated with the presence of EGFR mutations in NSCLC patients.8, 9 However, the etiology of these EGFR mutations in NSCLC is unknown. Taiwanese studies have suggested that a HPV 16/18 infection might be associated with this type of cancer in nonsmoking, female lung cancer patients.¹⁰ These findings suggest a possible association between EGFR mutations and a HPV infection. In addition, some patients with head and neck cancer were responsive to tyrosine kinase inhibitors (TKI) such as gefitinib.¹¹ Another study reported the presence of EGFR mutations in three out of 41 patients with head and neck cancer.¹² However, the clinical impact of EGFR mutations in head and neck cancer is not completely understood.

This study tested the hypothesis that a HPV infection is related to EGFR mutations in head and neck cancer. To accomplish this, the prevalence and association of EGFR mutations and HPV infections were evaluated in a subset of patients with head and neck cancer. Patients with tongue and tonsil cancer were selected because previous studies have suggested they have a different association with a HPV infection.4, 5, 7 The data on EGFR mutations and a HPV infection was compared with the clinical features of the patients.

Section snippets

Patients

Patients with squamous cell carcinoma of the tongue and tonsil were identified from the database of the Korea Cancer Centre Hospital (Seoul, Korea). The formalin-fixed paraffin-embedded tissues from 110 patients who underwent a local treatment modality such as surgery and radiation from July 1994 to December 2003 were examined. Patients who presented with a distant metastasis were excluded. Two pathologists reviewed all histology samples. Two cases with a sarcoma were excluded. The extent of

Patient characteristics and treatment

Table 1 shows the baseline characteristics of the patients. Sixty (74%) patients were male. The median age was 52 years. Thirty-nine percent of patients had never smoked. Seventy (65%) patients were diagnosed with tongue cancer. The proportion of patients with stage I–II, III and IV cancer was 50%, 28%, and 22%, respectively. Forty-four (41%) and 22 (20%) patients were treated with radiation or surgery, respectively. Combined modality treatment including neoadjuvant chemotherapy (chemotherapy

Discussion

There was no association found between EGFR mutations and a HPV infection in patients with tonsil and tongue cancer. Although recent studies have reported HPV positivity and EGFR mutantions in HNSCC, no patients who had an EGFR mutation were positive to the HPV in the present study.5, 12 The etiology of EGFR mutations remains unknown. Although this study was not designed to assess the survival outcomes of patients with EGFR mutations, there was no apparent difference in the survival outcome of

Conflict of interest statement

None declared.

Acknowledgement

This work was supported in part by AstraZeneca Pharmaceuticals.

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^☆: This work was presented at the 42nd annual meeting of the American Society of Clinical Oncology.

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EGFR mutations and human papillomavirus in squamous cell carcinoma of tongue and tonsil☆

Abstract

Introduction

Section snippets

Patients

Patient characteristics and treatment

Discussion

Conflict of interest statement

Acknowledgement

Mod Pathol

J Clin Virol

Int J Radiat Oncol Biol Phys

Eur J Cancer

Global and regional estimates of cancer mortality and incidence by site: II. Results for the global burden of disease 2000

BMC Cancer

Tobacco smoking, alcohol drinking, and cancer of the oral cavity and oropharynx among U.S. veterans

Cancer

Smoking and drinking in relation to cancers of the oral cavity, pharynx, larynx, and esophagus in northern Italy

Cancer Res

Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck

N Engl J Med

Evidence for a causal association between human papillomavirus and a subset of head and neck cancers

J Natl Cancer Inst

HPV infections and tonsillar carcinoma

J Clin Pathol

Human papillomavirus (HPV) in head and neck cancer

J Clin Virol

EGFR mutations in non-small-cell lung cancer: analysis of a large series of cases and development of a rapid and sensitive method for diagnostic screening with potential implications on pharmacologic treatment

J Clin Oncol

Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers

J Natl Cancer Inst

The association of human papillomavirus 16/18 infection with lung cancer among nonsmoking Taiwanese women

Cancer Res

Phase I study of gefitinib plus celecoxib in recurrent or metastatic squamous cell carcinoma of the head and neck

J Clin Oncol