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

Se Heon Kim, Bon Seok Koo, Suki Kang, Kyeongmee Park, Haeryoung Kim, Kyung Ryul Lee, Moo Joo Lee, Jong Man Kim, Eun Chang Choi, Nam Hoon Cho

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1418-1425
Number of pages8
JournalInternational Journal of Cancer
Volume120
Issue number7
DOIs
Publication statusPublished - 2007 Apr 1

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Tonsillar Neoplasms
Human papillomavirus 16
Neoplasms
Carcinogenesis
Cyclin B1
Cyclin A
Tonsillitis
Papillomavirus Infections
Palatine Tonsil
G1 Phase
S Phase
Uterine Cervical Neoplasms
Cell Cycle
Infection

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kim, Se Heon ; Koo, Bon Seok ; Kang, Suki ; Park, Kyeongmee ; Kim, Haeryoung ; Lee, Kyung Ryul ; Lee, Moo Joo ; Kim, Jong Man ; Choi, Eun Chang ; Cho, Nam Hoon. / HPV integration begins in the tonsillar crypt and leads to the alteration of p16, EGFR and c-myc during tumor formation. In: International Journal of Cancer. 2007 ; Vol. 120, No. 7. pp. 1418-1425.
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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.",
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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. / Kim, Se Heon; Koo, Bon Seok; Kang, Suki; Park, Kyeongmee; Kim, Haeryoung; Lee, Kyung Ryul; Lee, Moo Joo; Kim, Jong Man; Choi, Eun Chang; Cho, Nam Hoon.

In: International Journal of Cancer, Vol. 120, No. 7, 01.04.2007, p. 1418-1425.

Research output: Contribution to journalArticle

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AU - Kim, Se Heon

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AU - Park, Kyeongmee

AU - Kim, Haeryoung

AU - Lee, Kyung Ryul

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AU - Kim, Jong Man

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AU - Cho, Nam Hoon

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