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HPV integration begins in the tonsillar crypt and leads to the alteration of p16, EGFR and c-myc during tumor formation

Authors
 Se-Heon Kim  ;  Bon-Seok Koo  ;  Nam Hoon Cho  ;  Eun Chang Choi  ;  Jong Man Kim  ;  Moo Joo Lee  ;  Kyung Ryul Lee  ;  Haeryoung Kim  ;  Kyeongmee Park  ;  Suki Kang 
Citation
 INTERNATIONAL JOURNAL OF CANCER, Vol.120(7) : 1418-1425, 2007 
Journal Title
 INTERNATIONAL JOURNAL OF CANCER 
ISSN
 0020-7136 
Issue Date
2007
MeSH
Carcinoma, Squamous Cell/metabolism ; Carcinoma, Squamous Cell/pathology ; Carcinoma, Squamous Cell/virology* ; Cyclin A/genetics ; Cyclin A/metabolism ; Cyclin A1 ; Cyclin B/genetics ; Cyclin B/metabolism ; Cyclin B1 ; Cyclin-Dependent Kinase Inhibitor p16/genetics* ; DNA, Viral/genetics ; DNA, Viral/metabolism ; ErbB Receptors/genetics* ; Gene Amplification ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; In Situ Hybridization, Fluorescence ; Inhibitor of Apoptosis Proteins ; Microtubule-Associated Proteins/genetics ; Microtubule-Associated Proteins/metabolism ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Papillomaviridae/physiology* ; Proto-Oncogene Proteins c-myc/genetics* ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; S-Phase Kinase-Associated Proteins/genetics ; S-Phase Kinase-Associated Proteins/metabolism ; Survivin ; Tissue Array Analysis ; Tonsillar Neoplasms/metabolism ; Tonsillar Neoplasms/pathology ; Tonsillar Neoplasms/virology* ; Tonsillitis/genetics ; Tonsillitis/pathology ; Tonsillitis/virology* ; Virus Integration/physiology*
Abstract
The prevalence of human papillomavirus (HPV) infection is high in the oropharyngeal mucosal regions, of which the tonsil is the most commonly affected. There may be a link between HPV and the pathogenesis of tonsillar cancer (TC), because of common anatomical characteristics between cervical and tonsillar cancer. We aimed to clarify whether HPV directly affects the oncogenesis and biologic behavior of TC by making a comparison between infection prevalence, physical status and viral loading numbers, and clinicopathologic prognostic factors. To compare HPV-related molecules between TC and tonsillitis (CFT), p16, survivin, HIF-1α, skp-1, cyclin A, cyclin B1, c-myc and EGFR were investigated. We observed a significant difference in HPV prevalence between 52 TCs and 69 CFTs (73.1% vs. 11.6%), and most of the HPVs were type 16 (87.2%) and nonepisomal (94.1%). Most TCs associated with HPV arose from the tonsillar crypts, and tended to be inverted and poorly differentiated. Compared with HPV-negative TC, HPV-positive TC showed a strong association with p16 overexpression (p < 0.0001), and an inverse association with EGFR amplification (p = 0.0478). HPV-16 integration status was strongly associated with c-myc amplification (p = 0.034) and HIF-1α overexpression (p = 0.022). HPV-16 integration could be directly related to tonsillar carcinogenesis initially in tonsillar crypts, followed by cell cycle aberration such as p16 overexpression related to the G1-S phase.
Full Text
http://onlinelibrary.wiley.com/doi/10.1002/ijc.22464/abstract
DOI
10.1002/ijc.22464
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kang, Suki(강숙희) ORCID logo https://orcid.org/0000-0002-9957-3479
Koo, Bon Seok(구본석)
Kim, Se Heon(김세헌)
Cho, Nam Hoon(조남훈) ORCID logo https://orcid.org/0000-0002-0045-6441
Choi, Eun Chang(최은창)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/96136
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