Open AccessJournal Article
Etiological Involvement of Oncogenic Human Papillomavirus in Tonsillar Squamous Cell Carcinomas Lacking Retinoblastoma Cell Cycle Control
Thomas Andl,Tomas Kahn,Andreas Pfuhl,Teodora Nicola,Ralf Erber,Christian Conradt,Wolfgang Klein,M. Helbig,Andreas Dietz,Hagen Weidauer,Franz X. Bosch +10 more
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TLDR
Analysis of primary squamous cell carcinomas of the head and neck with respect to the presence of the retinoblastoma tumor suppressor protein, pRb, indicated a strong indication for a human papillomavirus-associated etiology of these tumors and suggested the functional inactivation of the pRB protein by the viral E7 gene product.Abstract:
Two hundred eight primary squamous cell carcinomas of the head and neck have been analyzed with respect to the presence of the retinoblastoma tumor suppressor protein, pRb. Of these, 23 tumors (11%) that preferentially localized to the tonsils revealed complete absence or dramatic reduction in the amount of pRb. Other cell cycle components, cyclin D1 and p16INK4A, which are intimately related to pRb through an autoregulatory loop, were also dramatically decreased or overexpressed, respectively, in these pRb-defective tumors. On the other hand, the majority of the pRb-defective tumors contained the wild-type p53 gene. No evidence was found for genetic defects at the Rb locus in these tumors. Very significantly, in 11 of 12 pRb-defective tonsillar tumors, but in none of 9 pRb-positive tonsillar tumors (P < 10[-7]), DNA of oncogenic human papillomavirus types was identified, providing a strong indication for a human papillomavirus-associated etiology of these tumors and suggesting the functional inactivation of the pRb protein by the viral E7 gene product. In comparison to all head and neck squamous cell carcinomas studied, the pRb-defective tonsillar tumors were in general more poorly differentiated (P = 0.0059), and they were all metastatic at the time of resection. Of particular clinical interest, despite these adverse histopathological factors, the clinical outcome for these patients was relatively favorable, strongly implying that the pRb-defective tumors responded uniformly well toward postoperative radiation therapy.read more
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Journal ArticleDOI
Evidence for a Causal Association Between Human Papillomavirus and a Subset of Head and Neck Cancers
Maura L. Gillison,Wayne M. Koch,Randolph B. Capone,Michael Spafford,William H. Westra,Li Wu,Marianna Zahurak,Richard W. Daniel,Michael P. Viglione,David Eric Symer,Keerti V. Shah,David Sidransky +11 more
TL;DR: It is suggested that HPV-positive oropharyngeal cancers comprise a distinct molecular, clinical, and pathologic disease entity that is likely causally associated with HPV infection and that has a markedly improved prognosis.
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HPV-associated head and neck cancer: a virus-related cancer epidemic
TL;DR: In this paper, the authors highlight current understanding of the epidemiology, biology, detection, and management of HPV-related oropharyngeal head and neck squamous cell carcinoma, and describe unresolved issues.
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Human Papillomavirus Infection as a Risk Factor for Squamous-Cell Carcinoma of the Head and Neck
Jon Mork,Anne Kveim Lie,Eystein Glattre,G. Hallmans,Egil Jellum,Pentti Koskela,Bjørn Møller,Eero Pukkala,John T. Schiller,Linda Youngman,Matti Lehtinen,Joakim Dillner,Joakim Dillner +12 more
TL;DR: HPV-16 infection may be a risk factor for squamous-cell carcinoma of the head and neck in subjects who were seropositive for HPV-16, and no increased risk was observed for other HPV types.
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Molecular Classification Identifies a Subset of Human Papillomavirus–Associated Oropharyngeal Cancers With Favorable Prognosis
Paul M. Weinberger,Ziwei Yu,Bruce G. Haffty,Diane Kowalski,Malini Harigopal,Janet L. Brandsma,Clarence T. Sasaki,John K. Joe,Robert L. Camp,David L. Rimm,Amanda Psyrri +10 more
TL;DR: A novel classification scheme that may have value for patient stratification for clinical trials testing HPV-targeted therapies is defined, namely HPV+/p16 high (class III) in oropharyngeal squamous cell carcinoma.
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Effect of HPV-Associated p16INK4A Expression on Response to Radiotherapy and Survival in Squamous Cell Carcinoma of the Head and Neck
Pernille Lassen,Jesper Grau Eriksen,Stephen Hamilton-Dutoit,Trine Tramm,Jan Alsner,Jens Overgaard +5 more
TL;DR: In this article, the authors evaluated p16 INK4A as a prognostic marker of treatment response and survival in a well-defined and prospectively collected cohort of patients treated solely with conventional radiotherapy in the Danish Head and Neck Cancer Group (DAHANCA) 5 trial.