Shahaf Givony1
1 Lithuanian University of Health Sciences. Academy of Medicine. Faculty of Odontology.
ABSTRACT
Oral Squamous Cell Carcinoma (OSCC) represents more than 90% of all oral cancer cases. It is considered one of the most frequent oral malignancies worldwide with a yearly prevalence of more than 500,000 new cases. OSCC may be found in various anatomical structures in the oral cavity, but usually appears on the lateral border of the tongue, the floor of the mouth and the lower lip. OSCC starts as a complicated process that depends on multiple risk factors such as excessive consumption of alcohol and long-term use of tobacco. During this process, epithelial cells are influenced by genetic mutations which eventually leads to the development of several neoplastic sites all over the oral cavity or in most the cases, will promote an already existed precancerous lesions to keep on growing. The TNM classification which is a famous method of oral cancer staging assists healthcare practitioners in diagnosis the stage of cancer in addition to the regular clinical evaluation. This classification also provides important data regarding the required way of treatment, which may be noninvasive, such as radiotherapy or invasive, such as surgery, which is usually the first option of treatment. OSCC rates of mortality among the general population cannot be completely vanished, but can definitely be reduced by few steps such as lifestyle changes and broad educational programs.
Keywords: Oral squamous cell carcinoma, Oral neoplasms, OSCC risk factors, Non-invasive and invasive detection technique.
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67
Medical Sciences 2020 Vol. 8 (13), p. 67-74
Oral squamous cell carcinoma (OSCC) an overview
Shahaf Givony
1
1
Lithuanian University of Health Sciences. Academy of Medicine. Faculty of Odontology.
ABSTRACT
Oral Squamous Cell Carcinoma (OSCC) represents more than 90% of all oral cancer cases. It is
considered one of the most frequent oral malignancies worldwide with a yearly prevalence of more than 500,000
new cases. OSCC may be found in various anatomical structures in the oral cavity, but usually appears on the
lateral border of the tongue, the floor of the mouth and the lower lip. OSCC starts as a complicated process that
depends on multiple risk factors such as excessive consumption of alcohol and long-term use of tobacco. During
this process, epithelial cells are influenced by genetic mutations which eventually leads to the development of
several neoplastic sites all over the oral cavity or in most the cases, will promote an already existed precancerous
lesions to keep on growing. The TNM classification which is a famous method of oral cancer staging assists
healthcare practitioners in diagnosis the stage of cancer in addition to the regular clinical evaluation. This
classification also provides important data regarding the required way of treatment, which may be noninvasive,
such as radiotherapy or invasive, such as surgery, which is usually the first option of treatment. OSCC rates of
mortality among the general population cannot be completely vanished, but can definitely be reduced by few
steps such as lifestyle changes and broad educational programs.
Keywords: Oral squamous cell carcinoma, Oral neoplasms, OSCC risk factors, Non-invasive and invasive
detection technique.
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Abbreviations
Oral squamous cell carcinoma (OSCC),
World Health Organization (WHO), Potentially
malignant disorders (PMDs), The International
Agency for Research on Cancer (IARC), South-
East Asia (SEARO), Europe region (EURO),
Human papilloma virus (HPV), Ultraviolet
radiation (UV), Epstein-barr virus (EBV),
Magnetic resonance imaging (MRI), Single-photon
emission computed tomography (SPECT),
Toluidine blue (TB), Orthopantomogram (OPG),
computed tomography perfusion (CTP),
Ultrasonography (USG).
Introduction
Oral squamous cell carcinoma (OSCC) is
rated among the 6
th
most frequent oral
malignancies, with a yearly prevalence of more
than 500,000 cases [1]. OSCC alone considered as
responsible for more than 90% of oral cancers
cases and have the highest rate of mortality
globally [2, 3, 4]. World Health Organization
(WHO) reports that the highest prevalence and
mortality of OSCC is divided to different regions
worldwide, such as South-East Asia (SEARO) and
Europe region (EURO). SEARO includes countries
such as Sri Lanka, India, Pakistan and Taiwan
while EURO includes countries such as France,
Hungary, Slovakia and Slovenia [4]. OSCC may
affect numerous anatomical structures such as the
lips, tongue, upper and lower gingiva, retromolar
triangle, alveolar mucosa, floor and roof (palate) of
the mouth, buccal mucosa, oropharynx and the
salivary glands [2, 7]. OSCC usually appears on the
lateral border of the tongue 40%, followed by the
floor of the mouth 30% and the lower lip [4, 7].
In 2005, WHO had advised to change the
term of “precancerous lesions” to the term
“potentially malignant disorders” (PMDs)
followed the fact that most of the OSCC cases were
a result of a previous precancerous lesions. The
PMDs include leukoplakia, erythroplakia, oral
lichen planus, oral submucous fibrosis, actinic
keratosis, discoid lupus erythematosus and palatal
lesions which may have been developed due to
smoking. Those disorders have a much higher
probability to become malignant compared to other
oral pathologies [3].
The ongoing researches and the
development of a new therapies, have not yielded
any significant improvement survival rate for the
patients and continue to be a challenging topic for
the medical community [4]. Accordingly, an early
diagnosis of oral PMDs will able practitioners to
supervise, diagnose and treat those disorders at the
initial stages of dysplasia or even carcinoma in situ
[3].
The aim of this article is to present a
general review of the literature regarding OSCC for
the general population and for the healthcare
practitioners.
Definition and risk factors
Oral cancer is a malignant neoplasm
which grows within the oral cavity. Approximately
90% of the oral cancers have a histological origin
of squamous cells and as a result, this type of
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cancer is typically defined as OSCC. The OSCC
has few levels of differentiation and a tendency for
regional lymph node metastasis [4].
The oral cavity is very accessible during
every clinical evaluation, but even to that fact, most
of the OSCC are been diagnosed at a very critical
and late stages. The main reasons for this situation
are the lack of knowledge from the patient’s side
and of course from the doctor side who did not
diagnose the condition properly. The late diagnosis
drastically reduces the rate of survival although the
broad possible methods of treatment [4].
The most significant risk factors for
OSCC, with a rate of over 90% are the long term
over consumption of alcohol and use of tobacco [4,
2].
Tobacco
Smoke of tobacco contains 3 groups of
chemicals such as nitrosamines, benzopyrenes and
aromatic amines which promotes cancer. Smokers
have a 3 times higher risk for developing an OSCC
compared to nonsmokers. In case of nonsmokers,
the involuntary smoking as a result from the
surrounding environment may increase the chance
of developing OSCC in 87% compared to those
who have not been in that environment. In addition,
smoking not only reduce the immunity of the oral
cavity, it also promotes gingivitis, periodontitis and
of course OSCC [4].
Alcohol
Is known as Ethanol and has a negative
effect on the organism. This effect acts on the local
level by allowing higher permeability into the oral
mucosa, dissolving lipid particles of the epithelium
and leading to epithelial atrophy in general. On the
systemic level, it has a mutagenic effect which
leads to a smaller salivary flow, decreased liver
competence to deal with carcinogenic chemicals
and eventually lead to impairment of the immunity
system. This impairment results an increased risk
for infections and new abnormal growth of tissue
[4].
Other risk factors
Less common but still possible risk
factors may be insufficient dental hygiene, genetic
tendency, chronic mechanical trauma by a sharp
object such as a tooth or a denture, chewing of
areca nut which occurs mostly in indo-asian
populations, human papilloma virus (HPV) which
according to the International Agency for Research
on Cancer (IARC) the HPV16 is responsible for the
cancers of the tonsils, pharynx and oral cavity
while HPV18 is responsible for oral cancer [4, 9].
In addition, ultraviolet radiation (UV) which is
mostly related to lip cancer, other viruses such as
hepatitis C and Epstein-barr virus (EBV) may be
also related to OSCC [4, 5].
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Carcinogenesis
Oral carcinogenesis is a very complicated
process which depends on multiple factors. During
this process, epithelial cells are influenced by
genetic mutations which eventually lead to a
several neoplastic sites all over the oral cavity,
those sites may develop over the years to the form
of OSCC. As a guideline, if an oral mucosal lesion
does not improve after three weeks, it must be
considered as a highly threatening condition which
will require biopsy and further histopathological
investigation [4].
Tnm stage classification
The most significant and predictive factor
which will determine the survival rate is the stage
of the tumor during the diagnosis [1]. The TNM
classification is a worldwide known method of oral
cancers staging which is used by healthcare
practitioners such as doctors, researchers and
cancer registration facilities [7, 10]. The initials, T
stands for tumor, N for lymph nodes and M for
metastases, are based on the measurements of the
disease prior to treatment [4]. The main role is to
provide an anatomical classification and to
properly describe the development of the cancer.
Specific description is the key for the selection of a
correct method of treatment, the possible outcome
and limitation for certain activities [10].
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Table. TNM definitions for oral cancer [4].
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Diagnostic methods
Diagnosis of a doubtful lesion most often
begin with the conventional oral examination,
which includes clinical evaluation and palpation of
the mucosa of the oral cavity under the lighting of
the dental chair [1]. The ability to make a diagnosis
at an early stage of OSCC is very important in order
to reduce the high rate of sickness and death among
the patients [6]. The most common methods used
for diagnosis of PMDs and OSCC in an early stage
are listed below [5].
Vital Staining
Methods such as Toluidine blue (TB),
Methylene blue staining, Rose bengal staining,
Lugol’s iodine staining. Staining with TB is a
known method for the identification of
premalignant and malignant lesions, which is
recommended to be as part of the clinical
evaluation of oral mucosal tissues, especially in
high-risk patients. Those methods are not
expensive, quite easy to apply and effective [3].
The staining implemented by various types of dyes
over the mucosa in order to mark the neoplastic
cells, cells with a high reproductive activity and to
indicate the specific areas for examination and
biopsy [5].
Light-based detection
In order to identify oral PMDs and OSCC
in their initial stage, several light-based devices
have been developed [3]. Those specific devices
can emit certain light which will reflect the
abnormal tissue and improve the clinical evaluation
[5].
Histological methods
Incisional and/or excisional biopsy are the
most accurate diagnostic methods and together
with the histopathological tests, remains as the
most reliable methods for OSCC diagnosis [5, 6].
Before the procedure of excisional biopsy, it is
important that the margins and depth of the tissue
will be verified of being a disease-free. Epithelial
dysplasia is known as the most prognostic sign of
any malignancy. WHO have defined that dysplasia
may be classified as mild, moderate and severe [5].
Cytological methods
Those are methods that use a microscope
in order to evaluate the cells which were obtained
from smears, scraping and needle aspiration over
various depts of the mucosa [5]. The common
findings are a typical mucosal lesion which at first
sight looks normal, but the prepared specimen will
present atypical cells. The cytological tests which
have been taken from the oral cavity may help to
identify and diagnose tissues with a high-risk or
even malignancy [5].
Imaging diagnostic methods
Those methods include local dental
radiographs, orthopantomogram (OPG), magnetic
resonance imaging (MRI), computed tomography
perfusion (CTP), C-arm CT, nuclear medicine such
as single-photon emission computed tomography
(SPECT), ultrasonography and combination of few
methods such as PET, CT/ MRI and SPECT/CT [5,
7].
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Management
The most common treatment methods for
oral cancer can be noninvasive, such as
radiotherapy in most of the cases or can be
invasive, such as surgery, which is usually the first
option of treatment despite the fact that
radiotherapy survival rate and control of the
anatomical site are similar [8, 9]. Those methods
can be provided separately or as a combination [8].
Radiotherapy may be provided separately
or as a combination with chemotherapy in order to
treat the initial tumor. It may be provided as
neoadjuvant therapy, which will decrease the tumor
size before the initial surgery. Radiotherapy may
also be provided as adjuvant therapy, which will
improve the efficiency of the initial therapy and by
doing so will prolong the survival rate, decrease the
change of possible recurrence and even improve
the symptoms of a late stage oral cancer [8].
Radiotherapy has some major drawbacks such as
xerostomia, osteoradionecrosis, mucositis and long
duration of treatment which in cases of proximity
to the bone and/or young patients are not preferable
[9].
The treatment methods for oral cancer
such as surgery, radiotherapy and chemotherapy
have a major effect on the patient’s quality of life
and considered as very harsh due to the location
and the obtrusive ways of treatment [7, 8]. The aim
of OSCC treatment methods is to treat the initial
tumor and to preserve as much as possible the
shape and function with a proper restoration [9].
Prevention
In order to reduce the OSCC mortality
among the general population, few steps should be
promoted. First, in case of patients with high risk,
the mortality may be reduced by promoting
lifestyle changes and apply clinical evaluation as a
part of a broad diagnostic program among the
population. Second, an educational program with
the basic knowledge regarding the OSCC should be
embedded in the population while a frequent
professional diagnostic and pathologic knowledge
should be provided to the healthcare practitioners.
Third, the ongoing and future researches regarding
the OSCC must continue in order to define the
particular etiological factors and biomarkers of the
disease [4].
Conclusion
In conclusion, the scientific literature
contains an enormous number of researches
regarding the OSCC and its comprehensive
information such as diagnostic methods, various
treatments and known risk factors. However, the
researches have not yielded any significant benefit
as the prevalence and rate of mortality of the OSCC
remains high.
Disclosure of conflict of interest
The authors declare no conflict of interest.
References
1. Giovannacci, I., Vescovi, P., Manfredi, M. and
Meleti, M. (2016). Non-invasive visual tools for
diagnosis of oral cancer and dysplasia: A
systematic review. Medicina Oral Patología Oral
y Cirugia Bucal, pp.e305-e315.
Journal of Medical Sciences. March 23, 2020 - Volume 8 | Issue 13. Electronic-ISSN: 2345-0592
74
2. Maleki, D., Ghojazadeh, M., Mahmoudi, S.,
Mahmoudi, S., Pournaghi-Azar, F., Torab, A., Piri,
R., Azami-Aghdash, S. and Naghavi-Behzad, M.
(2015). Epidemiology of Oral Cancer in Iran: a
Systematic Review. Asian Pacific Journal of
Cancer Prevention, 16(13), pp.5427-5432.
3. Liu, D., Zhao, X., Zeng, X., Dan, H. and Chen,
Q. (2016). Non-Invasive Techniques for Detection
and Diagnosis of Oral Potentially Malignant
Disorders. The Tohoku Journal of Experimental
Medicine, 238(2), pp.165-177.
4. Essentials of oral cancer. (2015). International
Journal of Clinical and Experimental Physiology, 8
(9), pp.11884-11894.
5. Carreras-Torras, C. and Gay-Escoda, C. (2015).
Techniques for early diagnosis of oral squamous
cell carcinoma: Systematic review. Medicina Oral
Patología Oral y Cirugia Bucal, pp.e305-e315.
6. Mascitti, M., Orsini, G., Tosco, V.,
Monterubbianesi, R., Balercia, A., Putignano, A.,
Procaccini, M. and Santarelli, A. (2018). An
Overview on Current Non-invasive Diagnostic
Devices in Oral Oncology. Frontiers in
Physiology, 9.
7. Pałasz, P., Adamski, Ł., Górska-Chrząstek, M.,
Starzyńska, A. and Studniarek, M. (2017).
Contemporary Diagnostic Imaging of Oral
Squamous Cell Carcinoma – A Review of
Literature. Polish Journal of Radiology, 82,
pp.193-202.
8. Ketabat, F., Pundir, M., Mohabatpour, F.,
Lobanova, L. and Koutsopoulos, S. (2019).
Controlled Drug Delivery Systems for Oral Cancer
Treatment—Current Status and Future
Perspectives. Pharmaceutics, 11(7), p.302.
9. Arya, S., Rane, P. and Deshmukh, A. (2014).
Oral cavity squamous cell carcinoma: Role of
pretreatment imaging and its influence on
management. Clinical Radiology, 69(9), pp.916-
930.
10. Huang, S. and O’Sullivan, B. (2017). Overview
of the 8th Edition TNM Classification for Head and
Neck Cancer. Current Treatment Options in
Oncology, 18(7).