Lack of evidence of human papillomavirus-induced squamous cell carcinomas of the oral cavity in southern Germany.

Abstract

OBJECTIVES:

The aim of the present study was to identify HPV-attributable SCC of the oral cavity (OSCC) in a cohort of patients from southern Germany.

MATERIALS AND METHODS:

A sensitive PCR-enzyme immunoassay (EIA) was followed by a more specific in situ hybridization (ISH) to detect high risk human papillomavirus (HPV). An immunohistochemical dual-staining for p16(INK4a) and the proliferation marker Ki-67 was used to assess whether co-expression of p16(INK4a)/Ki-67 is a better surrogate marker for HPV in OSCC than p16(INK4a) alone, based on the hypothesis that combined p16(INK4a) and Ki-67 expression might specifically discriminate oncogene-induced p16(INK4a) expression from cell-cycle arrest-inducing senescence-associated p16(INK4a) expression.

RESULTS:

HPV-DNA by PCR-EIA could be detected in 25.1% (69/275) of the tumors, but ISH was negative in all of them. Diffuse p16(INK4a) overexpression was detected in 11 HPV PCR-positive tumors, but also in 6 HPV PCR-negative tumors. p16(INK4a)-expressing cells in diffusely positive tumors co-expressed Ki-67, irrespective of the HPV status. Neither the sole HPV status nor combined HPV/p16(INK4a) status nor the sole p16(INK4a) status was significantly associated with disease free or overall survival, however a trend towards better overall survival of patients whose tumor expressed p16(INK4a) in a focal pattern (=p16(INK4a)-positive/Ki-67-negative cells) compared to no p16(INK4a) expression (p=0.09) was observed.

CONCLUSION:

Viral DNA can be detected in some tumors by a sensitive PCR, but absence of ISH signals indicates that the HPV-attributable fraction is smaller than estimated from PCR positivity. p16(INK4a)/Ki-67 co-expression is detectable in a fraction of OSCC irrespective of the HPV status.

• Authors: Miriam Reuschenbach, Katinka Kansy, Kira Garbe, Svetlana Vinokurova, Christa Flechtenmacher, Csaba Toth, Elena-Sophie Prigge, Oliver C Thiele, Siegmar Reinert, Jürgen Hoffmann, Magnus von Knebel Doeberitz, Kolja Freier
• Journal: Oral oncology (Oral Oncol) Vol. 49 Issue 9 Pg. 937-942 (Sep 2013) ISSN: 1879-0593 [Electronic] England
• PMID: 23608471 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Biomarkers, Tumor

Topics

• Adult
• Biomarkers, Tumor (analysis)
• Carcinoma, Squamous Cell (epidemiology, virology)
• Female
• Genotype
• Germany (epidemiology)
• Humans
• Male
• Middle Aged
• Mouth Neoplasms (epidemiology, virology)
• Papillomaviridae (isolation & purification)
• Prognosis