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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
Author(s) -
Kim SeHeon,
Koo BonSeok,
Kang Suki,
Park Kyeongmee,
Kim Haeryoung,
Lee Kyung Ryul,
Lee Moo Joo,
Kim Jong Man,
Choi Eun Chang,
Cho Nam Hoon
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22464
Subject(s) - tonsil , carcinogenesis , hpv infection , cancer research , pathogenesis , cancer , biology , medicine , cervical cancer , pathology
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. © 2006 Wiley‐Liss, Inc.