HPV DNA, E6*I-mRNA expression and p16INK4A immunohistochemistry in head and neck cancer - how valid is p16INK4A as surrogate marker?
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HPV DNA, E6*I-mRNA expression and p16INK4A immunohistochemistry in head and neck cancer - how valid is p16INK4A as surrogate marker? / Hoffmann, Markus; Tribius, Silke; Quabius, Elgar Susanne; Henry, Hannes; Pfannenschmidt, Saskia; Burkhardt, Claudia; Görögh, Tibor; Halec, Gordana; Hoffmann, Anna Sophie; Kahn, Tomas; Röcken, Christoph; Haag, Jochen; Waterboer, Tim; Schmitt, Markus.
in: CANCER LETT, Jahrgang 323, Nr. 1, 1, 2012, S. 88-96.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - HPV DNA, E6*I-mRNA expression and p16INK4A immunohistochemistry in head and neck cancer - how valid is p16INK4A as surrogate marker?
AU - Hoffmann, Markus
AU - Tribius, Silke
AU - Quabius, Elgar Susanne
AU - Henry, Hannes
AU - Pfannenschmidt, Saskia
AU - Burkhardt, Claudia
AU - Görögh, Tibor
AU - Halec, Gordana
AU - Hoffmann, Anna Sophie
AU - Kahn, Tomas
AU - Röcken, Christoph
AU - Haag, Jochen
AU - Waterboer, Tim
AU - Schmitt, Markus
PY - 2012
Y1 - 2012
N2 - It has been proposed that p16(INK4A) qualifies as a surrogate marker for viral oncogene activity in head and neck cancer (HNSCC). By analyzing 78 HNSCC we sought to validate the accuracy of p16(INK4A) as a reliable marker of active HPV infections in HNSCC. To this end we determined HPV DNA (HPVD) and E6*I mRNA (HPVR) expression status and correlated these results with p16(INK4A) staining. In tonsillar SCC 12/20 were HPVD+ and 12/12 of these showed active HPV infections whereas in non-tonsillar SCC 10/58 were HPVD+ and 5/10 showed active HPV infections. Thus, we prove about 8% of non-tonsillar SCC to be also correlated with HPV-associated carcinogenesis. Strikingly, 3/14 (21.4%) of tonsillar and non-tonsillar HPVD+/HPVR+ cases did not show p16(INK4A) overexpression and these cases would have been missed when applying initial p16(INK4A) staining only. However, in 13 cases negative for HPV, DNA p16(INK4A) was overexpressed. In conclusion, our data confirm tonsillar SCC to be predominantly but not only associated with active HPV infections. Furthermore, our data show that p16(INK4A) overexpression is not evident in a subgroup of HNSCC with active HPV infection. Definitive HPV data should therefore be utilized in diagnostics and treatment modalities of HPV positive and HPV negative HNSCC patients, resulting in a paradigm shift regarding these obviously different tumor entities.
AB - It has been proposed that p16(INK4A) qualifies as a surrogate marker for viral oncogene activity in head and neck cancer (HNSCC). By analyzing 78 HNSCC we sought to validate the accuracy of p16(INK4A) as a reliable marker of active HPV infections in HNSCC. To this end we determined HPV DNA (HPVD) and E6*I mRNA (HPVR) expression status and correlated these results with p16(INK4A) staining. In tonsillar SCC 12/20 were HPVD+ and 12/12 of these showed active HPV infections whereas in non-tonsillar SCC 10/58 were HPVD+ and 5/10 showed active HPV infections. Thus, we prove about 8% of non-tonsillar SCC to be also correlated with HPV-associated carcinogenesis. Strikingly, 3/14 (21.4%) of tonsillar and non-tonsillar HPVD+/HPVR+ cases did not show p16(INK4A) overexpression and these cases would have been missed when applying initial p16(INK4A) staining only. However, in 13 cases negative for HPV, DNA p16(INK4A) was overexpressed. In conclusion, our data confirm tonsillar SCC to be predominantly but not only associated with active HPV infections. Furthermore, our data show that p16(INK4A) overexpression is not evident in a subgroup of HNSCC with active HPV infection. Definitive HPV data should therefore be utilized in diagnostics and treatment modalities of HPV positive and HPV negative HNSCC patients, resulting in a paradigm shift regarding these obviously different tumor entities.
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Immunohistochemistry
KW - RNA, Messenger/analysis
KW - Biological Markers/analysis
KW - Carcinoma, Squamous Cell/metabolism/virology
KW - Cyclin-Dependent Kinase Inhibitor p16/analysis
KW - DNA, Viral/analysis
KW - Head and Neck Neoplasms/metabolism/virology
KW - Multiplex Polymerase Chain Reaction
KW - Oncogene Proteins, Viral/analysis
KW - Papillomavirus Infections/complications/diagnosis
KW - Tonsillar Neoplasms/metabolism/virology
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Immunohistochemistry
KW - RNA, Messenger/analysis
KW - Biological Markers/analysis
KW - Carcinoma, Squamous Cell/metabolism/virology
KW - Cyclin-Dependent Kinase Inhibitor p16/analysis
KW - DNA, Viral/analysis
KW - Head and Neck Neoplasms/metabolism/virology
KW - Multiplex Polymerase Chain Reaction
KW - Oncogene Proteins, Viral/analysis
KW - Papillomavirus Infections/complications/diagnosis
KW - Tonsillar Neoplasms/metabolism/virology
M3 - SCORING: Journal article
VL - 323
SP - 88
EP - 96
JO - CANCER LETT
JF - CANCER LETT
SN - 0304-3835
IS - 1
M1 - 1
ER -