gms | German Medical Science

76. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e. V.

Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e. V.

04.05. - 08.05.2005, Erfurt

Is p16INK4A overexpression a reliable biomarker for oncogenic human papillomavirus infection in normal tonsils?

Meeting Abstract

  • corresponding author Ernst-Jan Speel - Department of Molecular Cell Biology, University of Maastricht, Netherlands
  • Boris Klingenberg - Department of Molecular Cell Biology, University of Maastricht, Netherlands
  • Harriet Hafkamp - Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Maastricht, Netherlands
  • Annick Haesevoets - Department of Molecular Cell Biology, University of Maastricht, Netherlands
  • Piet Slootweg - Department of Pathology, University Medical Center Nijmegen, Netherlands
  • Soenke Weissenborn - Institute for Virology, University of Cologne, Germany
  • Peter Klussmann - Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Germany
  • Johannes Manni - Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Maastricht, Netherlands

Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie. 76. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e.V.. Erfurt, 04.-08.05.2005. Düsseldorf, Köln: German Medical Science; 2005. Doc05hno221

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hno2005/05hno048.shtml

Veröffentlicht: 22. September 2005

© 2005 Speel et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Recent analyses have provided evidence that human papillomavirus (HPV) is an etiological risk factor for head and neck squamous cell carcinomas (HNSCC). Oncogenic HPV, mainly type 16, has been strongly associated with tonsillar carcinomas [1], [2] and appears to be of prognostic significance. Because HPV-positive tonsillar carcinomas also accumulate p16INK4A this inhibitor of cell proliferation might be a candidate biomarker for clinical diagnosis. Data on the value of p16INK4A overexpression to predict HPV infection in normal and dysplastic tonsil tissue, however, are scarce. Here we studied the prevalence of p16INK4A overexpression by using immunohisto-chemistry on 4 micrometer thick formalin-fixed, paraffin-embedded sections from normal tonsil samples of 263 patients (mean age: 29.2; range 12-70 years). These patients were treated in 1997-1998 for non-oncologic reasons, which mostly included tonsillectomy. Strong p16INK4A-positive and a number of weakly positive and negative samples were subsequently screened by PCR for the presence of oncogenic HPV subtypes, adenovirus and cytomegalo-virus DNA. All 263 samples contained squamous cell epithelium and 187/263 harbored lymphoid tissue, 177 of which contained tonsil crypt epithelium. Diffuse cytoplasmic and nuclear p16INK4A staining was only identified in crypt epithelium (49/177; 27.7%) and germinal centers (52/187; 27.8%), which was strongly associated with each other (p=0.001). PCR analysis of 28 p16INK4A-stained tonsil samples (17 strongly positive, 5 weakly positive and 6 negative) revealed 2 cases harboring HPV DNA, i.e. one with HPV 16 and 18 (associated with p16INK4A overexpression), and the other with HPV 16, 18 and 68 (p16INK4A negative). Our results show a rather high percentage of normal tonsillar crypt epithelia with increased p16INK4A expression, which only in 1 case appears to be associated with HPV. Thus p16INK4A should be used with caution as biomarker for HPV on normal tonsil tissue. Other mechanisms of p16INK4A activation are therefore implicated, which do not point to adenovirus or CMV infection.

This study was supported in part by the Medical Research Foundation ("Profileringsfonds") of the University Hospital Maastricht, grant no. PF126.


References

1.
Hafkamp. Int. J. Cancer. 2003;107:394-400.
2.
Hafkamp. Acta Otolaryngol. 2004;124:520-6.