Comparative analysis of HPV16 gene expression profiles in cervical and in oropharyngeal squamous cell carcinoma.

Andrea Cerasuolo,Luigi Buonaguro,Stefano Greggi,Marianna Tortora,Maria Grazia Maglione,Noemy Starita,Maria Lina Tornesello,Franco M Buonaguro,Clorinda Annunziata,Gerardo Botti,Giovanni Stellato,Franco Ionna,Simona Losito

doi:10.18632/oncotarget.15977

Andrea Cerasuolo, Luigi Buonaguro + Show 11 more

Open Access

https://doi.org/10.18632/oncotarget.15977

Copy DOI

Abstract

Human papillomavirus type 16 (HPV16) is the major cause of cervical cancer and of a fraction of oropharyngeal carcinoma. Few studies compared the viral expression profiles in the two types of tumor. We analyzed HPV genotypes and viral load as well as early (E2/E4, E5, E6, E6*I, E6*II, E7) and late (L1 and L2) gene expression of HPV16 in cervical and oropharyngeal cancer biopsies. The study included 28 cervical squamous cell carcinoma (SCC) and ten oropharyngeal SCC, along with pair-matched non-tumor tissues, as well as four oropharynx dysplastic tissues and 112 cervical intraepithelial neoplasia biopsies. Viral load was found higher in cervical SCC (<1 to 694 copies/cell) and CIN (<1 to 43 copies/cell) compared to oropharyngeal SCC (<1 to 4 copies/cell). HPV16 E2/E4 and E5 as well as L1 and L2 mRNA levels were low in cervical SCC and CIN and undetectable in oropharynx cases. The HPV16 E6 and E7 mRNAs were consistently high in cervical SCC and low in oropharyngeal SCC. The analysis of HPV16 E6 mRNA expression pattern showed statistically significant higher levels of E6*I versus E6*II isoform in cervical SCC (p = 0.002) and a slightly higher expression of E6*I versus E6*II in oropharyngeal cases. In conclusion, the HPV16 E5, E6, E6*I, E6*II and E7 mRNA levels were more abundant in cervical SCC compared to oropharyngeal SCC suggesting different carcinogenic mechanisms in the two types of HPV-related cancers.

Highlights

Cancers of the cervix and of the head and neck region are among the most common tumors in the world accounting for approximately 528,000 and 686,000 new cases in 2012, respectively [1]
In this study the viral load and the expression pattern of Human papillomavirus type 16 (HPV16) early (E2, E4, E5, E6, E6*I, E6*II, E7) and late (L1 and L2) genes were analyzed in cervical squamous cell carcinoma (SCC) and paired tissues, in cervical intraepithelial neoplasia (CIN), in oropharyngeal SCC and paired non-tumor tissues, as well as in oropharyngeal dysplasia to uncover differences in human papillomaviruses (HPV)-related transformation mechanisms in different types of HPV-related tumors
In agreement with previous studies, we found that HPV16 was the most frequent genotype in cervical and oropharyngeal cancer [12, 14, 41]

Summary

Introduction

Cancers of the cervix and of the head and neck region are among the most common tumors in the world accounting for approximately 528,000 and 686,000 new cases in 2012, respectively [1]. Cervical cancer incidence has decreased over the last decades in many high-resource countries, due to the introduction of cervical screening programs, a stable or increasing incidence has been reported in low-income countries [2,3,4]. During the same time period an increased incidence of oropharyngeal cancer has been observed in European countries, in Australia, Canada, and in the United States suggesting a new and emerging risk factor among young men [7, 8]. Twelve high risk human papillomaviruses (HPV) have been recognized as the necessary cause of cervical cancer and of a subgroup of head and neck tumors. The viral DNA has been identified in more than www.impactjournals.com/oncotarget

Objectives

Methods

Results

Conclusion