Oncotarget

Research Papers: Pathology:

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

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

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Oncotarget. 2017; 8:34070-34081. https://doi.org/10.18632/oncotarget.15977

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Abstract

Andrea Cerasuolo1, Clorinda Annunziata1, Marianna Tortora1, Noemy Starita1, Giovanni Stellato2, Stefano Greggi2, Maria Grazia Maglione3, Franco Ionna3, Simona Losito4, Gerardo Botti4, Luigi Buonaguro1, Franco M. Buonaguro1 and Maria Lina Tornesello1

1 Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Napoli, Italy

2 Gynecology Oncology Division, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Napoli, Italy

3 Department of Maxillofacial and Ear Nose and Throat Surgery, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Napoli, Italy

4 Department of Pathology, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Napoli, Italy

Correspondence to:

Maria Lina Tornesello, email:

Keywords: HPV16; E6 gene; E7 gene; cervical carcinoma; cervical intraepithelial neoplasia; Pathology Section

Received: February 07, 2016 Accepted: February 28, 2017 Published: March 07, 2017

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.


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