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Oral Oncol. 2015 Feb;51(2):112-8. doi: 10.1016/j.oraloncology.2014.11.002. Epub 2014 Nov 26.

Prevention of head and neck squamous cell carcinoma: removing the "chemo" from "chemoprevention".

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Department of Hematology and Medical Oncology, The Winship Cancer Institute of Emory University, Atlanta, GA, USA.
Department of Medicine, Division of Oncology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.
Department of Medical Oncology, Antwerp University Hospital, Edegem, Belgium.
Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia.
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
University of Udine School of Medicine, Udine, Italy.
Department of Otolaryngology-Head and Neck Surgery, Radboud University Medical Center, Nijmegen, The Netherlands.
University of Udine School of Medicine, Udine, Italy. Electronic address:


The concept of chemoprevention whereby the use of a systemic agent is intended to halt the carcinogenesis process has been an attractive topic in head and neck squamous cell carcinoma (HNSCC). Yet, despite the significant efforts over the past decades and the substantial gain in knowledge of the biology of pre-malignant lesions of the head and neck, no tangible indications for chemoprevention have emerged for this disease. The negative results observed in the earlier larger studies using retinoids did not encourage further trials with these agents. Attention has been more recently focused on epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) as well as cyclo-oxygenase 2 (COX-2) inhibitors with early studies showing encouraging responses but rather poor tolerance to therapy. Natural compounds have gained more interest recently given preclinical evidence of activity as well as a low side effect profile. We herein offer a comprehensive overview of the field of chemoprevention in HNSCC with an in depth analysis of the challenges we face and discuss a road map for future directions.


Carcinoma in situ; Chemoprevention; Head and neck cancer; Oral dysplasia; Premalignant lesions; Second primary tumor

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