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Involvement of intact HPV16 E6/E7 gene expression in head and neck cancers with unaltered p53 status and perturbed pRb cell cycle control

Oncogene volume 21, pages 1510–1517 (2002)Cite this article

Abstract

We have identified parameters which define a causal role of HPV16 in head and neck cancer. Twenty-eight tumours which were typed positive for HPV16 DNA, were comprehensively analysed for expression of the viral oncogenes E6 and E7, the status of the p53 gene, and the protein status of pRb and p16INK4a. In a subset of cases, we have searched for integrated viral DNA, and have determined the genomic status of the E6 gene. Expression of E6/E7 was found in 12 tumours most of which were derived from the oropharynx, whereas p53 mutations were present in 13 tumours from various sites. The tumours either carried p53 mutations but did not express E6/E7, or they did express E6/E7 but were p53-wild-type. Coexistence of E6/E7 expression with a mutated p53 was found in only one case. Strikingly, in most p53-mutated tumours without E6/E7 expression, we found the E6 gene to be disrupted. E6/E7 expression was associated with reduced pRb and overexpressed p16INK4a. Viral-cellular fusion transcripts were found in two cases. Our data demonstrate that HPV16 DNA-positivity in head and neck cancers is not indicative of a causal role. A causal role of HPV16 in head and neck cancer is defined by: E6/E7 expression, viral integration with an intact E6 gene, and perturbation of pRb cell cycle control. Mostly, the p53 gene is wild-type.

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Acknowledgements

We are greatly indebted to Drs A Dietz, C Reißer, AJ Tasman and F Wallner for collecting and processing the tissue specimens, P Tomakidi and L Gissmann for fruitful discussions, and H Weidauer for support. We also thank S Huntgeburth, A Schuhmann, A Kohl, C Lokrey and F Devens for their excellent technical assistance. P Benjamin is acknowledged for photographical work.

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Authors and Affiliations

  1. Molekularbiologisches Labor, Universitäts-Hals-Nasen-Ohrenklinik, Im Neuenheimer Feld 400, Heidelberg, 69120, Germany

    Tina Wiest, Christel Enders & Franz X Bosch

  2. Angewandte Tumorvirologie, F0600, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, Heidelberg, 69120, Germany

    Elisabeth Schwarz

  3. Pathologisches Institut der Universität Heidelberg, Im Neuenheimer Feld 220, Heidelberg, 69120, Germany

    Christa Flechtenmacher

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  1. Tina Wiest
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Correspondence to Franz X Bosch.

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Wiest, T., Schwarz, E., Enders, C. et al. Involvement of intact HPV16 E6/E7 gene expression in head and neck cancers with unaltered p53 status and perturbed pRb cell cycle control. Oncogene 21, 1510–1517 (2002). https://doi.org/10.1038/sj.onc.1205214

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