oral cancer olcna

Preface
Oral Cancer
Guest Editor
Oral cancer is the sixth most common cancer in the United States. Each
year, 30,000 Americans and more than 300,000 people worldwide will be di-
agnosed as having oral cancer, and 8000 to 10,000 deaths in the United
States will result. Unfortunately, although significant advances have been
made in the diagnosis and treatment of oral cancer, the survival rate has
not meaningfully changed in 30 years.
This issue reviews recent advances in the approach to oral cancer. An ex-
perienced interdisciplinary team from MD Anderson Cancer Hospital and
the University of Colorado Cancer Center describes how new technologies
in dentistry, cell biology, engineering, imaging, and computer science are
finding their way into the mainstream of oral cancer management.
Despite our better understanding of the cell biology and behavior of oral
cancer, significant challenges lie ahead if we are to improve survival and re-
duce the morbidity from treatment. Present techniques for the early detec-
tion of early cancer are not sufficiently sensitive or specific. One half of
patients still present with advanced-stage disease. Despite the description
of hundreds of biomarkers, none are universally accepted in biostaging. A
disturbing number of patients are developing oral cancer, frequently at an
early age, with few known risk factors. Predictions of the response to treat-
ment or the likelihood of developing neck or distant metastases are largely
inaccurate. We still need an imaging technique that can accurately identify
microscopic, nonpalpable neck metastases. Chemoradiation has too high
a rate of disabling side effects. It is hoped that the advances described in
the book will translate into better treatment results, sooner rather than
later.
Arlen D. Meyers, MD, MBA
0030-6665/06/$ - see front matter Ó2005 Elsevier Inc. All rights reserved.
doi:10.1016/j.otc.2005.11.006 oto.theclinics.com
Otolaryngol Clin N Am
39 (2006) xi–xii

I sincerely appreciate the opportunity to serve as Guest editor of this is-
sue, and I thank the authors for their valuable contributions and insights.
Most of all, thanks to Kathleen.
Arlen D. Meyers, MD, MBA
Department of Otolaryngology
University of Colorado Health Sciences Center
4200 East 9th Avenue
Denver, CO 80262, USA
E-mail address: [e-mail]
xii PREFACE

Molecular Biology of Oral Cavity
Squamous Cell Carcinoma
Michael E. Kupferman, MD,
Jeffrey N. Myers, MD, PhD*
Department of Head and Neck Surgery, M. D. Anderson Cancer
Center of the University of Texas, 1515 Holcombe Boulevard, Unit 441,
Houston, TX 77030, USA
Oral cavity squamous cell carcinoma (OCSCC) is diagnosed in approxi-
mately 12,000 Americans and results in the death of more than 5000 each
year [1]. Worldwide, OCSCC is a major health care problem, accounting
for more than 274,000 newly diagnosed cancers, and is the most frequently
diagnosed cancer in some regions of the world [2]. In Central and Western
Europe, the mortality rates for OCSCC range from 29 to 40 per 100,000 [3].
There is also a high incidence of this disease in India and parts of Southeast
Asia. Worldwide, OCSCC is the eleventh most common cancer. Although
improvements have been achieved in surgical techniques, radiation therapy
protocols, and chemotherapeutic regimes [4], the overall 5-year survival rate
for this disease remains at 50% and has not significantly improved in the
past 30 years [5].
It is now apparent that improved treatment for OCSCC hinges on under-
standing the underlying dysregulation of the molecular processes in
OCSCC. Already, a better understanding of the fundamental mechanisms
of carcinogenesis and metastasis has yielded some promising targets for
treatment in various cancers [6]. Because newer diagnostic strategies and
novel agents that target specific molecular pathways are increasingly being
implemented in the clinical setting, it behooves the surgeon treating this dis-
ease to have a basic understanding of tumor biology. This article focuses on
the current knowledge of the molecular processes that underlie tumorigene-
sis and metastasis in OCSCC.
* Corresponding author.
E-mail address: [email protected] (J.N. Myers).
0030-6665/06/$ - see front matter Ó2005 Elsevier Inc. All rights reserved.
doi:10.1016/j.otc.2005.11.003 oto.theclinics.com
Otolaryngol Clin N Am
39 (2006) 229–247

Field cancerization and the genetic progression of oral cavity
squamous cell carcinoma
The process by which a normal cell is transformed into a malignant one has
been the focus of tumor biology for decades and has resulted in the description
of several diverse mechanisms of carcinogenesis. Two of these, which are crit-
ical to OCSCC tumorigenesis, are field cancerization and genetic progression.
Field cancerization
Chronic exposure to tobacco and alcohol has long been associated with
the development of OCSCC. Further, patients diagnosed with OCSCC
who have been chronically exposed to tobacco and alcohol are at high
risk for recurrences and second primary lesions. To explain the development
of multiple OCSCC recurrences and second primary tumors in distinct areas
of histologically normal upper aerodigestive tract mucosa, Slaughter and
colleagues [7] described the phenomenon of field cancerization. It was pro-
posed that regions of grossly normal mucosa have the following properties
that increase the likelihood of transformation and recurrence:
1. Tumors in the oral cavity arise in areas of histologically dysplastic
mucosa.
2. Tumors in the oral cavity are surrounded by dysplastic mucosa.
3. The coalescence of multiple small lesions results in clinically isolated
lesions.
4. Local recurrences and second primaries arise from the remnant dysplas-
tic epithelium.
It is thought that chronic exposure to environmental mutagens in tobacco
and alcohol or infection with human papillomavirus (HPV) can contribute
to the development of these areas of condemned mucosa. The evolution of
this process is detailed here.
During the past 4 decades extensive research has been done on the mech-
anisms of field cancerization, and a unifying theory has begun to emerge.
Fearon and Vogelstein [8,9] were the first to describe a coherent model
for the genetic basis of a human cancer, specifically colon cancer. The fol-
lowing four features define this model:
1. The activation of oncogenes and the inactivation of tumor suppressor
genes are the results of early genetic alterations that accompany the phe-
notypic changes that occur in the progression from colonic adenomas to
carcinomas.
2. At least four mutations are necessary for the transformation.
3. The overall accumulation of mutations, rather than the order in which
they occur, is primarily responsible for carcinogenesis.
4. Alterations in tumor suppressor gene function may not require ‘‘two
hits’’ for promoting the development of tumors.
230 KUPFERMAN & MYERS