HPV DNA, E6^*I-mRNA expression and p16^INK4A immunohistochemistry in head and neck cancer - How valid is p16^INK4A as surrogate marker?

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• 作者：Markus Hoffmann^a ; ^{mhoffmann@hno.uni-kiel.de} ; Silke Tribius^b ; Elgar Susanne Quabius^c ; ^d ; Hannes Henry^a ; Saskia Pfannenschmidt^a ; Claudia Burkhardt^a ; Tibor G&ouml ; r&ouml ; gh^a ; Gordana Halec^e ; Anna Sophie Hoffmann^f ; Tomas Kahn^g ; Christoph R&ouml ; cken^h ; Jochen Haag^h ; Tim Waterboer^e ; Markus Schmitt^e
• 关键词：BSGP5+/6+-PCR&ndash ; MPG ; Multiplex HPV genotyping ; Human papillomavirus ; HPV ; E6mRNA ; Head and neck cancer ; HNSCC ; p16 ; Viral load
• 刊名：Cancer Letters
• 出版年：2012
• 期刊代码：44_03043835
• 类别：med
• 出版时间：1 October, 2012
• 卷：323
• 期：1
• 页码：88-96
• 文件大小：668 K

摘要

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.