• 12/19/2006
  • Milan, Italy
  • Lisa Licitra et al.
  • Journal of Clinical Oncology, Vol 24, No 36 (December 20), 2006: pp. 5630-5636

Purpose:
Human papillomavirus (HPV) DNA tumors actively integrating the E6 and E7 oncogenes have a distinct biologic behavior resulting in a more favorable prognosis. To which extent the viral integration by itself, and/or the associated wild-type (wt) TP53 status, and/or a functional p16 contribute to prognosis is unclear.

Patients and Methods:
To clarify how the presence of high-risk (HR) -HPV, TP53, and p16INK4a status interact with clinical outcome, we considered a retrospective series of 90 consecutive oropharyngeal cancer patients treated primarily with surgery.

Results:
Seventeen (19%) patients showed integrated HPV 16 DNA (HPV positive), wt TP53 in all but two patients, normal p16INK4a in 15 assessable patients, and p16 expression in all 17 patients. Thirty-five patients (39%), two of whom were HPV positive, harbored TP53 mutations. p16INK4a deletion and p16 null immunophenotype occurred in 28 and 58 patients, respectively, and was similarly distributed in both patients with mutated TP53 (48% and 82%, respectively) and in patients with wt TP53 (46% and 77%, respectively). Statistical analysis showed that HPV-positive status significantly affects all investigated end points: overall survival (P = .0018), incidence of tumor relapse (P = .0371), and second tumor (P = .0152), whereas TP53 and p16INK4a status and p16 expression were not prognostic by themselves.

Conclusion:
Our molecular and clinical results are in agreement with previous findings but provide additional information into the biologic mechanisms involved in HR-HPV oropharyngeal cancer in comparison to HPV-negative tumors. According to the reduced risk of relapse and second tumors associated with HR-HPV positivity of oropharyngeal cancer, the therapeutic strategy and follow-up procedures should be reviewed.

Authors:
Lisa Licitra, Federica Perrone, Paolo Bossi, Simona Suardi, Luigi Mariani, Raffaella Artusi, Maria Oggionni, Chiara Rossini, Giulio Cantù, Massimo Squadrelli, Pasquale Quattrone, Laura D. Locati, Cristiana Bergamini, Patrizia Olmi, Marco A. Pierotti, Silvana Pilotti

Authors’ affiliation:
From the Head and Neck Cancer Medical Oncology Unit, Unit of Experimental Molecular Pathology, Medical Statistics and Biometry, Department of Head and Neck Surgery, Department of Pathology, Radiotherapy Department, and Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori; and Fondazione Italiana per la Ricerca sul Cancro (FIRC) Institute of Molecular Oncology, Milan, Italy

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