Distinctive Expression and Amplification of Genes at 11q13 in Relation to HPV Status with Impact on Survival in Head and Neck Cancer Patients.

Francisco Hermida-Prado,Sofía Menéndez,Pablo Albornoz-Afanasiev,Eva Allonca,Saúl Álvarez-Teijeiro,Rocío Granda-Diaz,M Villaronga,Juan Rodrigo,Xavier León,Laia Alemany,Nagore Del-Rio-Ibisate,Aurora Astudillo,Laura Alonso-Durán,Juana García-Pedrero,Marisa Mena,René Rodríguez

doi:10.3390/jcm7120501

Abstract

Clear differences have been established between head and neck squamous cell carcinomas (HNSCC) depending on human papillomavirus (HPV) infection status. This study specifically investigated the status of the CTTN, CCND1 and ANO1 genes mapping at the 11q13 amplicon in relation to the HPV status in HNSCC patients. CTTN, CCND1 and ANO1 protein expression and gene amplification were respectively analyzed by immunohistochemistry and real-time PCR in a homogeneous cohort of 392 surgically treated HNSCC patients. The results were further confirmed using an independent cohort of 279 HNSCC patients from The Cancer Genome Atlas (TCGA). The impact on patient survival was also evaluated. CTTN, CCND1 and ANO1 gene amplification and protein expression were frequent in HPV-negative tumors, while absent or rare in HPV-positive tumors. Using an independent validation cohort of 279 HNSCC patients, we consistently found that these three genes were frequently co-amplified (28%) and overexpressed (39–46%) in HPV-negative tumors, whereas almost absent in HPV-positive tumors. Remarkably, these alterations (in particular CTTN and ANO1 overexpression) were associated with poor prognosis. Taken together, the distinctive expression and amplification of these genes could cooperatively contribute to the differences in prognosis and clinical outcome between HPV-positive and HPV-negative tumors. These findings could serve as the basis to design more personalized therapeutic strategies for HNSCC patients.

Highlights

Head and neck cancer represents a heterogeneous group of tumors that accounts for about 5% of the total annual worldwide cases of cancer, usually associated with poor prognosis [1,2]; its incidence and other main features can significantly vary from one region to another
When analyzing the correlations with human papillomavirus (HPV) infection status, we consistently found that CCND1, ANO1, and CTTN gene amplification inversely correlated with HPV status (Table 2)
W(≥he4ncaonpaileysz)ing the correlatio2n4s with HPV infection0 status, we consistently found that CCND1, ANO1, and CTTN gene amplification inversely correlated with HPV status (Table 2)

Summary

Introduction

Head and neck cancer represents a heterogeneous group of tumors that accounts for about 5% of the total annual worldwide cases of cancer, usually associated with poor prognosis [1,2]; its incidence and other main features can significantly vary from one region to another. The most prevalent histological type in head and neck cancers is the squamous cell carcinoma (HNSCC), and it is widely accepted that the most important risk factors are tobacco and alcohol consumption [1,3,4]. More than 90% of HPV-related HNSCC tumors are caused by one specific virus type, the HPV-16, which leads to HPV-related anogenital tumors [4,5]. On this basis, epidemiological studies have correlated HPV-positive tumors with sexual behaviors, suggesting that the risk increases with the number of sexual partners and is more frequent in men [4,5]

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Results

Conclusion