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Viral DNA integration and methylation of human papillomavirus type 16 in high-grade oral epithelial dysplasia and head and neck squamous cell carcinoma.

Authors :
Khanal S
Shumway BS
Zahin M
Redman RA
Strickley JD
Trainor PJ
Rai SN
Ghim SJ
Jenson AB
Joh J
Source :
Oncotarget [Oncotarget] 2018 Jul 13; Vol. 9 (54), pp. 30419-30433. Date of Electronic Publication: 2018 Jul 13 (Print Publication: 2018).
Publication Year :
2018

Abstract

This study evaluated the integration and methlyation of human papillomavirus type 16 (HPV16) in head and neck squamous cell carcinoma (HNSCC) and its oral precursor, high-grade oral epithelial dysplasia (hgOED). Archival samples of HPV16-positive hgOED ( N = 19) and HNSCC ( N = 15) were evaluated, along with three HNSCC (UMSCC-1, -47 and -104) and two cervical cancer (SiHa and CaSki) cell lines. HgOED cases were stratified into three groups with increasing degrees of cytologic changes (mitosis, karyorrhexis and apoptosis). The viral load was higher and the E2/E6 ratio lower (indicating a greater tendency toward viral integration) in group 3 than in groups 1 or 2 ( p = 0.002, 0.03). Methylation was not observed in hgOED cases and occurred variably in only three HNSCC cases (26.67%, 60.0% and 93.3%). In HNSCC cell lines, lower E7 expression correlated with higher levels of methylation. HgOED with increased cytologic change, now termed HPV-associated oral epithelial dysplasia (HPV-OED), exhibited an increased viral load and a tendency toward DNA integration, suggesting a potentially increased risk for malignant transformation. More detailed characterization and clinical follow-up of HPV-OED patients is needed to determine whether HPV-OED is a true precursor to HPV-associated HNSCC and to clarify the involvement of HPV in HNSCC carcinogenesis.<br />Competing Interests: CONFLICTS OF INTEREST All authors have no conflicts of interest.

Details

Language :
English
ISSN :
1949-2553
Volume :
9
Issue :
54
Database :
MEDLINE
Journal :
Oncotarget
Publication Type :
Academic Journal
Accession number :
30100997
Full Text :
https://doi.org/10.18632/oncotarget.25754