Human Papillomavirus 16 DNA Methylation Patterns and Investigation of Integration Status in Head and Neck Cancer Cases

Author:

Zygouras Ioannis1,Leventakou Danai2,Pouliakis Abraham2ORCID,Panagiotou Styliana1,Tsakogiannis Dimitris3ORCID,Konstantopoulos Georgios1,Logotheti Eirini1,Samaras Menelaos2,Kyriakopoulou Zaharoula4ORCID,Beloukas Apostolos56ORCID,Pateras Ioannis S.2,Delides Alexandros7,Psyrri Amanda8,Panayiotides Ioannis G.2,Yiangou Minas1,Kottaridi Christine1ORCID

Affiliation:

1. Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece

2. 2nd Department of Pathology, University General Hospital “Attikon”, School of Medicine, National and Kapodistrian University of Athens, 12464 Athens, Greece

3. Research Center, Hellenic Anticancer Institute, 10680 Athens, Greece

4. Department of Environment, School of Technology, University of Thessaly, Gaiopolis Campus, 41500 Larissa, Greece

5. Department of Biomedical Sciences, University of West Attica, 12243 Athens, Greece

6. National AIDS Reference Centre of Southern Greece, School of Public Health, University of West Attica, 11521 Athens, Greece

7. 2nd Department of Otolaryngology, University General Hospital “Attikon”, School of Medicine, National and Kapodistrian University of Athens, 12464 Athens, Greece

8. 2nd Department of Internal Medicine-Propaedeutic, University General Hospital “Attikon”, School of Medicine, National and Kapodistrian University of Athens, 12464 Athens, Greece

Abstract

Persistent high-risk human papillomavirus (HPV) infection is a pivotal factor in the progression of cervical cancer. In recent years, an increasing interest has emerged in comprehending the influence of HPV on head and neck squamous cell carcinoma (HNSCC). Notably, it is well established that HPV-associated HNSCC show cases with distinct molecular and clinical attributes compared to HPV-negative cases. The present study delves into the epigenetic landscape of HPV16, specifically its L1 gene and untranslated region (UTR), through pyrosequencing, while the HPV16 DNA physical status was evaluated using E2/E6 ratio analysis in HPV16-positive HNSCC FFPE biopsies. Our findings reveal substantial methylation across six sites within the HPV16 L1 gene and seven sites in the UTR. Specifically, methylation percentages of two L1 CpG sites (7136, 7145) exhibit significant associations with tumor histological grade (p < 0.01), while proving concurrent methylation across multiple sites. The HPV16 DNA physical status was not correlated with the methylation of viral genome or tumor characteristics. This is the first study that examines epigenetic modifications and the HPV16 DNA physical status in Greek HNSCC patients. Our findings suggest an orchestrated epigenetic modulation among specific sites, impacting viral gene expression and intricate virus–host interactions.

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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