This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Licitra, L. Articles by Pilotti, S. Search for Related Content PubMed PubMed Citation Articles by Licitra, L. Articles by Pilotti, S.

High-Risk Human Papillomavirus Affects Prognosis in Patients With Surgically Treated Oropharyngeal Squamous Cell Carcinoma

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

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

Address reprint requests to Lisa Licitra, MD, Head and Neck Cancer Medical Oncology Unit, Cancer Medicine Department Istituto Nazionale per lo Studio e la Cura dei Tumori, 20133 Milano, Italy; e-mail: lisa.licitra{at}istitutotumori.mi.it

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 p16^INK4a 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 p16^INK4a in 15 assessable patients, and p16 expression in all 17 patients. Thirty-five patients (39%), two of whom were HPV positive, harbored TP53 mutations. p16^INK4a 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 p16^INK4a 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.

Supported in part by grants from the Italian Association for Cancer Research (AIRC) Grant (S.P.) and Consiglio Nazionale delle Ricerche/Ministero dell'Universitá e della Ricerca (CNR/MIUR).

L.L. and S.P. contributed equally to this work.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

This article has been cited by other articles:

				F. P. Worden, B. Kumar, J. S. Lee, G. T. Wolf, K. G. Cordell, J. M.G. Taylor, S. G. Urba, A. Eisbruch, T. N. Teknos, D. B. Chepeha, et al. Chemoselection As a Strategy for Organ Preservation in Advanced Oropharynx Cancer: Response and Survival Positively Associated With HPV16 Copy Number J. Clin. Oncol., July 1, 2008; 26(19): 3138 - 3146. [Abstract] [Full Text] [PDF]

				B. Kumar, K. G. Cordell, J. S. Lee, F. P. Worden, M. E. Prince, H. H. Tran, G. T. Wolf, S. G. Urba, D. B. Chepeha, T. N. Teknos, et al. EGFR, p16, HPV Titer, Bcl-xL and p53, Sex, and Smoking As Indicators of Response to Therapy and Survival in Oropharyngeal Cancer J. Clin. Oncol., July 1, 2008; 26(19): 3128 - 3137. [Abstract] [Full Text] [PDF]

				M. L. Gillison, G. D'Souza, W. Westra, E. Sugar, W. Xiao, S. Begum, and R. Viscidi Distinct Risk Factor Profiles for Human Papillomavirus Type 16-Positive and Human Papillomavirus Type 16-Negative Head and Neck Cancers J Natl Cancer Inst, March 19, 2008; 100(6): 407 - 420. [Abstract] [Full Text] [PDF]

				D. Beutner, J.-P. Klussmann, O. Guntinas-Lichius, F. Perrone, P. Bossi, L. Licitra, W. Koch, M. L. Poeta, and J. Manola TP53 mutations in head and neck cancer. N. Engl. J. Med., March 13, 2008; 358(11): 1194 - 1195. [Full Text] [PDF]

				C. Fakhry, W. H. Westra, S. Li, A. Cmelak, J. A. Ridge, H. Pinto, A. Forastiere, and M. L. Gillison Improved Survival of Patients With Human Papillomavirus-Positive Head and Neck Squamous Cell Carcinoma in a Prospective Clinical Trial J Natl Cancer Inst, February 20, 2008; 100(4): 261 - 269. [Abstract] [Full Text] [PDF]

				W. H. Westra, J. M. Taube, M.L. Poeta, S. Begum, D. Sidransky, and W. M. Koch Inverse Relationship between Human Papillomavirus-16 Infection and Disruptive p53 Gene Mutations in Squamous Cell Carcinoma of the Head and Neck Clin. Cancer Res., January 15, 2008; 14(2): 366 - 369. [Abstract] [Full Text] [PDF]

				N. Choong and E. Vokes Expanding Role of the Medical Oncologist in the Management of Head and Neck Cancer CA Cancer J Clin, January 1, 2008; 58(1): 32 - 53. [Abstract] [Full Text] [PDF]

				M. L. Gillison Human Papillomavirus and Prognosis of Oropharyngeal Squamous Cell Carcinoma: Implications for Clinical Research in Head and Neck Cancers J. Clin. Oncol., December 20, 2006; 24(36): 5623 - 5625. [Full Text] [PDF]