The Journal of International Medical Research

2010; 38: 737 – 749 [first published online as 38(3) 3]

Early Diagnosis of Oral Cancer

T BAYKUL1, HH YILMAZ1, Ü AYDIN3, MA AYDIN4, MÇ AKSOY1 AND D YILDIRIM2
1
Department of Oral and Maxillofacial Surgery and 2Department of Oral Diagnosis and
Radiology, Faculty of Dentistry, Süleyman Demirel University, Isparta, Turkey; 3Department
of Oral Diagnosis and Radiology, Faculty of Dentistry, Başkent University, Ankara, Turkey;
4
Department of Plastic and Reconstructive Surgery, Faculty of Medicine, Süleyman Demirel
University, Isparta, Turkey

Survival rates for oral cancer are very
poor, at approximately 50% overall, and
have not improved markedly in recent
decades despite advances in therapeutic
interventions. Detecting oral cancer at an
early stage is believed to be the most
effective means of reducing rates of death,
morbidity and disfigurement from this
disease. Tobacco and alcohol consumption
and pre-malign lesions are the most
common aetiological factors. The
proportion of patients presenting with
oral cancer at an advanced stage is
troubling. Early diagnosis is the most
effective way of reducing the individual
burden of the disease, decreasing
morbidity and mortality and improving
quality of life. For early diagnosis,
healthcare providers should perform oral
cancer examinations as part of their
patient care regime, and need to be
knowledgeable about early signs of oral
carcinoma. Oral cancer awareness among
the public should also be improved.

KEY WORDS: ORAL CANCER; EARLY DIAGNOSIS; CANCER AWARENESS; REVIEW

Introduction at an early stage, when lesions are small or

Oral cancer is a global health problem with
increasing incidence and mortality rates;
more than 500 000 patients are estimated to
have oral cancer worldwide.1 Oral cavity
squamous cell carcinoma (SCC) accounts for
90 – 94% of oral cancers, but various
malignancies, such as salivary gland
malignancies, soft and hard tissue sarcomas
and metastatic cancers, also occur.2,3
Survival rates for oral cancer are very poor,
at approximately 50% overall, and have not
improved markedly in the last few decades
despite advances in therapeutic
interventions. 4,5
It is now well established
that early diagnosis of oral malignancies is
an effective way of improving the clinical
outcome for patients.5 Detecting oral cancer
localized, is believed to be the most effective
means to reduce death, morbidity and
disfigurement from this disease.6
Risk factors
The consumption of tobacco and alcohol is
strongly associated with the subsequent
emergence of oral tumours.7 – 12 In the USA,
74% of the risk of oral cancer can be
attributed to tobacco and alcohol use,
particularly when these substances are
consumed heavily.13 A minority of patients
develop a cancer in the apparent absence of
one or both of these risk factors.14 In a
Kentucky population, Hodge et al.15 reported
a rate of 3.4% for oral cancers in non-users of
tobacco. Rich and Radden16 found that

737
 T Baykul, HH Yilmaz, Ü Aydin et al.
Early diagnosis of oral cancer
Australian patients with oral cancer who
had never used tobacco or alcohol developed
carcinomas on the buccal side of the teeth
and upper alveolar ridge, and data from a
study in Amsterdam17 are consistent with
this finding. There was a clear majority of
women, especially older women, among
non-users of both tobacco and alcohol, and
comparatively few cancers of the floor of the
mouth among female non-users.14 None of
these studies on the rare cases that occur in
non-users of tobacco and alcohol impacts
the evidence that these agents are far and
away the major risk factors.14 There is strong
evidence for an aetiological relationship
between oral cancer and the use of alcohol
and tobacco, the latter being the single most
important cause of oral cancer; moreover,
these two agents act synergistically with
regard to carcinogenic potential.18
Oral cancer is strongly associated with
male gender and advanced age; 92.3% of
oral cancer cases reported to the National
Cancer Institute’s Surveillance, Epidemiology
and End Results (SEER) programme in the
USA between 1985 and 1996 occurred
among individuals aged 40 years and
older.13 Nearly half (49.6%) of the incident
cases of oral cancer reported were among
people aged 65 years and older.13
Comparing 30-year incidence trends in oral
cancer in 49 different cancer registries,
Franceschi et al.19 found that the incidence
among men was highest in northern France,
southern India, a few areas of central and
eastern Europe, and Latin America, while
the incidence among women was highest in
India. Historically, oral SCC has typically
been associated with men aged 60 years and
older who are regular consumers of tobacco
and alcohol products, but the patient
demographic is changing.14,20,21 A steady
increase in the incidence of oral SCC has
been observed in patients younger than 40
738
years, and women without risk factors are
particularly affected.22 – 24
It is well established that most oral cavity
SCCs develop from pre-malign lesions and
cause noticeable clinical and histological
changes in the oral mucosa.25 Erythroplasia
in particular is accepted as an early
presentation of SCC.25,26 In a study of 236
patients with asymptomatic oral
carcinomas, 64% of the lesions were red,
12% were predominantly white and 23%
were white and red in equal proportions.27,28
The literature reports a wide range (11 –
36%) for the overall risk of malign
transformation, depending on the type of
lesion being followed and the length of
follow-up.25,29 In a cohort study, four out of
192 patients developed an SCC of the oral
mucosa during follow-up; all lesions were of
the lichenoid type. In view of these results,
the authors advised monitoring twice a year
for the early detection of possible malign
transformation in patients with oral
lichenoid lesions.30 Viral infections, immune
defects and nutritional inadequacies are the
main hypothetical factors in this group of
patients.14 Strong evidence for an
aetiological relationship between human
papillomavirus and a subset of oral cancers
has been noted by Gillison et al.,31,32 who
raised the possibility of sexual transmission.
People with poor oral hygiene appear to
have an increased risk of oral SCC
independently of any effect of tobacco,
alcohol or other well-proven risk factors.33,34
Clinical features
Many oral cancers do not present visually
detectable signs or symptoms while in the
pre-malign or localized stage, i.e. when they
are most treatable.35 The most common sites
of oral SCC are the dorsal and lateral borders
of the tongue (40%), floor of the mouth
(30%), retromolar trigone, the buccal
 T Baykul, HH Yilmaz, Ü Aydin et al.
Early diagnosis of oral cancer
mucosa and the maxillary and mandibular
gingiva.36,37 These are areas covered by thin,
non-keratinized mucosa that is more
permeable to carcinogens than keratinized
mucosa.38 Waldron and Schafer,39 in a large
series of 3526 patients, emphasized specific
high-risk locations, which included the floor
of the mouth and ventral tongue regions,
and demonstrated a 40% risk of dysplasia or
carcinoma at the time of the initial biopsy
from the floor of the mouth.
There is no common appearance of oral
cancers, but two critical signs that are
present in almost all cancers are induration
and fixation.4 Most oral SCCs will present in
one of four ways: a red patch, a white patch,
an endophytic ulcerative lesion, or, less
commonly, a more exophytic mass with
rolled margins, central ulceration and tissue
friability.18 Warning features of oral
carcinoma may be red lesions
(erythroplasia), mixed red and white lesions,
an indurated lump or ulcer, ulcer with
fissuring or raised exophytic margins, pain
or numbness, loose teeth, a non-healing
extraction socket, fixation of tissues to
deeper or overlying mucosa, lymph node
enlargement, dysphagia and weight loss.40
Much of the literature has focused on the
relationship of symptoms and pain during
and after cancer treatment; there has been
very little research to elucidate the first signs
and symptoms that a patient notices.41,42
The few studies that have investigated this
issue have focused either on pain as a first
symptom or on the delay after the onset of
symptoms before presenting to the
clinician.43,44 Various attempts at clinically
highlighting probable dysplastic areas
before biopsy have not been shown to be
absolutely reliable, but may be of some help
in suspicious conditions in patients at high
risk of oral cancer.40 Currently available
diagnostic technologies other than biopsy
739
and histopathological examination are vital
staining, biomarkers, DNA ploidy, brush
biopsy and optical techniques.40
Causes of delay
Despite the ready accessibility of the oral
cavity to direct examination, these
malignancies are often still not detected
until a late stage and, as a result, the
survival rate for oral cancer has remained
essentially unchanged over the past three
decades.45 The 5-year survival rate for small
tumours approaches 80% but falls to 30% for
stage 4 disease.46 – 48 Late diagnosis results in
more expensive, aggressive and disfiguring
treatments, lower survival rates, lower
function and lower quality of life among
survivors.49 – 51 Oral SCC is painless and
asymptomatic in the early stages and
prompts the patient’s self-referral only when
symptoms develop.38 As early symptoms of
oral cancer are often unspectacular, they are
easily attributed to trivial causes by
uninformed patients.52 Socioeconomic status
and barriers to access to a healthcare
professional may be causes of patient delay,
which is defined as the period between the
patient first noticing a symptom and their
first consultation with a healthcare
professional concerning the symptom.52 – 54
Public awareness of oral cancer seems
alarmingly low, as demonstrated by
Horowitz et al.,55 who found that fewer than
25% of subjects could name alcohol or
tobacco as risk factors.5 Use of a cancer
information leaflet had a significant effect in
raising the long-term level of knowledge of
oral cancer in the general public and also
had a secondary effect on disease awareness
in the locale.56 Lack of knowledge is only
part of the problem, as a comparison of
studies by McLeod et al.57 and Schnetler58
provides evidence to suggest that campaigns
to raise public awareness have made little
 T Baykul, HH Yilmaz, Ü Aydin et al.
Early diagnosis of oral cancer
difference to patient delay.
Professional delay may be defined as the
period from the patient’s first consultation
with a healthcare professional to the
definitive pathological diagnosis.59 The
causes of professional delay have been
suggested to include deficient clinical
examination, non-specific clinical signs, a
low index of suspicion, lack of familiarity
and experience with the disease, and
comorbidity.53,54,60,61 In a study designed to
identify which factors are related to specialist
delay and to determine the length of the
diagnostic pathway in oral cancer patients,
Brouha et al.62 found that patients with large
tumours experienced significantly less
specialist delay compared with those having
small tumours.
Holmes et al.63 reported that
asymptomatic patients are more likely to be
referred for a biopsy after a routine oral
examination at a general dental practice
than at a primary medical practice. On the
contrary, Kowalski et al.64 indicated that
patients were three times more likely to
obtain care from a primary care physician
than from a dentist before diagnosis. Gellrich
et al.7 evaluated 1761 patients retrospectively
and 1519 of the patients indicated the type
of medical professional who treated their
first symptoms.7 Dentists treated first
symptoms in 40% of the patients, family
physicians in 27%, and oral and
maxillofacial surgeons in 23%. Kowalski et
al.64 obtained a similar result in a
prospective study of patients with oral
cancer. McCann et al.65 and Hahn66
illustrated the important role of dentists in
oral cancer detection compared with family
physicians. In contrast, Schnetler58 found
that family physicians diagnosed
carcinomas and lymph node metastases
earlier than dentists. Guggenheimer et al.67
suggested that a medical care provider was
740
more likely to encounter a patient at risk
than a dentist, because of co-existing
medical conditions. Patients at risk of oral
cancers who use tobacco and alcohol are
four to six times more likely to seek
physician services than dental services.68
Some studies have emphasized the
importance of a partnership between
dentists and family physicians in increasing
the likelihood of early detection of oral
cancer.69,70
The proportion of patients presenting with
oral cancer at an advanced stage is
troubling. Early diagnosis is the most
effective way to reduce the individual burden
of the disease, decrease the morbidity and
mortality rates, and improve quality of
life.71,72 Thus, comprehensive examination
of the head, neck and oral cavity should be
part of all medical and dental examinations.
At the same time, education of healthcare
workers in order to improve their ability to
recognize oral malignant and pre-malignant
lesions might be implemented in order to
obtain an early definitive diagnosis.53
Tumour stage at diagnosis is still
recognized as the most important prognostic
marker for oral SCC in particular, and
advanced tumour stages are frequently
associated with high mortality rates.73,74
Studies indicate that delay may be related to
the patient’s passive attitude or the
specialist’s failure to interpret the symptoms
readily and correctly.64,67,75 Some studies
examining the delay in diagnosis have
revealed an association between professional
delay and the presence of an advanced
tumour at diagnosis,72,76,77 while others have
not found such an association.61,64,78 – 80
Guggenheimer et al.61 failed to find an
association between professional delay and
the stage at diagnosis, but Wildt et al.81
found that tumour size correlated
significantly with professional delay but not
 T Baykul, HH Yilmaz, Ü Aydin et al.
Early diagnosis of oral cancer
with patient delay. Brouha et al.62 reported
patient delay as a factor contributing to
diagnostic delay in late-stage disease.
Tumour growth rate may play a role in the
relationship between diagnostic delay and
tumour stage, as patients with aggressive
tumours and poor prognosis do not usually
present diagnostic delay, whereas tumours
with low proliferation rates elicit a good
prognosis despite a long diagnostic delay.46
This paradoxical circumstance, in which
diagnostic delay, tumour stage and tumour
prognosis are inversely related, seems to
suggest that stage at diagnosis is affected
more by the biology of the cancer than by
the diagnostic delay.82,83 Measures to
minimize the diagnostic delay can, however,
lead to diagnosis at an earlier stage of the
disease, which usually results in a better
prognosis, a satisfactory clinical outcome
and, in most instances, a cure.18,46
Cases studied at the Faculty
of Dentistry at Süleyman
Demirel University
During the period of 1999 – 2009, the
authors studied 23 patients (12 males, 11
females) who were referred to the Faculty of
Dentistry at Süleyman Demirel University,
Isparta, Turkey, with various complaints but
diagnosed as having oral cancer. The age
range was 6 – 82 years, with a mean ± SD
age of 57 ± 19 years. All patients were
examined clinically and radiographically by
both the Department of Oral Diagnosis and
Radiology and the Department of Oral and
Maxillofacial Surgery at the university. After
confirming the diagnosis histopatho-
logically, 12 patients were operated on in the
Department of Plastic and Reconstructive
Surgery by authors T.B., M.A.A. and M.C.A.
Radiotherapy and chemotherapy were
performed at another oncology centre. Table
741
1 shows the distribution of age, gender,
localization, complaints, treatment and
follow-up data of the patients.
The most common localizations in the 10
SCC cases were the maxillary and
mandibular gingiva (five cases), followed
by the retromolar trigone (two), buccal
mucosa (two) and the left lower lateral
border of the tongue (one case). Although
these high-risk sites are all easily visible on
physical examination, all patients
experienced a delay in diagnosis. As all the
SCC patients had a late diagnosis, it was
not possible to observe whether there was a
predisposing lesion at the early stage (Fig.
1); four of the 10 SCC patients were smokers
and none was a consumer of alcohol
products. There were four males and six
females amongst the 10 SCC patients,
which shows the demographic change in
the male to female ratio that has occurred
in terms of an increased incidence in
women without known risk factors.
The other malignancies among these
cases were lymphoma, adenoid cystic
carcinoma, sinonasal carcinoma, verrucous
carcinoma, epidermoid carcinoma,
malignant melanoma, multiple myeloma
and osteosarcoma. Lymphoma is the most
frequently seen malignancy after SCC in the
oral cavity84 (Fig. 2). Preferred sites in the
oral cavity are the tonsillar region, gingiva
and hard palate.85 One of the other
prevalent cancer types in the oral cavity is of
salivary gland origin.85 Minor salivary
glands are anatomically abundant in the
oral cavity and oral tumours should,
therefore, be considered in the differential
diagnosis of lesions, especially those in the
retromolar area, the palate and the floor of
the mouth.85,86 Survival is poorest for
malignant melanoma (Fig. 3) and sarcoma.
The low survival rate of patients with
metastatic tumours is usually related to the
 TABLE 1:
The distribution of age, gender, localization, complaints, treatment and follow-up data of the 23 patients (12 males and 11
females) who were referred to the Faculty of Dentistry at Süleyman Demirel University and diagnosed as having oral cancer
Duration
of life
after
Age diagnosis/
Patient (years) Sex Complaint Lymphadenopathy Malignancy Location Treatment Metastasis follow-up
1 72 M Tooth luxation Bilateral High-grade Right maxillar Chemotherapy N/A 1 month
submandibular lymphoma pre-molar– (died)
molar region
2 69 M Non-healing No metastasis Lymphoma Right maxillar Chemotherapy N/A N/A
extraction socket molar region
for 3 weeks
3 6 F Tooth luxation + No metastasis High-grade Left mandibular Chemotherapy No 3 years
dental abscess lymphoma deciduous second
molar–permanent

742
first molar
4 37 M Non-healing ulcer Bilateral High-grade Left maxillar Chemotherapy Bone, brain 4 years
for 2 months submandibular lymphoma molar region (died)
5 48 M Painful swelling and No metastasis Lymphoma Right maxillar Chemotherapy N/A 2 months
nasal congestion for pre-molar-molar (died)
Early diagnosis of oral cancer

20 days region
6 75 F Oral ulcer for 5 Left SCC Right mandibular Not available N/A N/A
T Baykul, HH Yilmaz, Ü Aydin et al.

months and submandibular– canine–molar

prosthodontic cervical–axillary region
rehabilitation
7 46 F Oral ulcer for 2 Bilateral SCC Left maxillar Surgical excision Brain 1.5 years
weeks submandibular molar region + chemotherapy (died)
8 63 M Rapidly growing, Left submandibular SCC Left mandibular Surgical excision No 1 year
painful, retromolar region
haemorrhagic mass
for 1.5 months
 TABLE 1 (continued):
The distribution of age, gender, localization, complaints, treatment and follow-up data of the 23 patients (12 males and 11
females) who were referred to the Faculty of Dentistry at Süleyman Demirel University and diagnosed as having oral cancer
Duration
of life
after
Age diagnosis/
Patient (years) Sex Complaint Lymphadenopathy Malignancy Location Treatment Metastasis follow-up
9 72 M Rapidly growing Left submandibular Epidermoid Left buccal Surgical excision Right orbital 4 years
mass carcinoma mucosa + chemotherapy region, (died)
right buccal
mucosa
10 62 F Paraesthesia in No metastasis Multiple Maxilla, mandible Chemotherapy Vertebral, 9 months
lower lip for 3 myeloma cranial bone (died)
months metastasis
11 46 M A painful swelling No metastasis Sinonasal Left maxillar Surgical excision Lung 3 years

743
and nasal flow for carcinoma molar region
1.5 years
12 64 M Pigmented mass in Bilateral Malignant Left maxillar Maxillectomy No follow- 1.5 years
the palatal region submandibular melanoma palatal region up
for 2 months
13 74 F Non-healing oral No metastasis Adenoid Anterior Mandibular No 2 years
Early diagnosis of oral cancer

ulcer for 3 years cystic mandible resection +

carcinoma chemotherapy
T Baykul, HH Yilmaz, Ü Aydin et al.

14 22 F Non-healing dental No metastasis Adenoid Left maxilla Subtotal Lung 5 years

abscess for 3 cystic maxillectomy +
months carcinoma chemotherapy
15 74 F Painful swelling Left submandibular Verrucous Left maxilla Not available N/A 15 days
carcinoma (died)
16 75 F Oral ulcer for 5 – No metastasis SCC Right mandibular Not available N/A N/A
6 months and canine–molar
prosthodontic region
rehabilitation
 TABLE 1 (continued):
The distribution of age, gender, localization, complaints, treatment and follow-up data of the 23 patients (12 males and 11
females) who were referred to the Faculty of Dentistry at Süleyman Demirel University and diagnosed as having oral cancer
Duration
of life
after
Age diagnosis/
Patient (years) Sex Complaint Lymphadenopathy Malignancy Location Treatment Metastasis follow-up
17 26 M Paraesthesia in Left Osteosarcoma Left mandibular Resection and No 1.5 years
lower lip and huge submandibular pre-molar region reconstruction
mass in mandible in another
hospital
18 54 M Mass in right No metastasis SCC Maxillar anterior Resection No 2 years
maxillar canine region

744
region
19 50 M Mass in right No metastasis SCC Right maxilla Resection, No 4 years
maxilla subtotal
maxillectomy
20 82 F Painful ulcer due No metastasis SCC Tongue — left Resection No 3 years
to dentures lower part
Early diagnosis of oral cancer

21 78 M Tooth luxation, N/A SCC Left maxillary Resection, No 5 years

swelling sinus chemotherapy,
T Baykul, HH Yilmaz, Ü Aydin et al.

radiotherapy
22 55 F Ulcer in right Right SCC Right cheek N/A N/A N/A
buccal mucosa submandibular
23 65 F Non-healing oral Left SCC Left retromolar N/A N/A N/A
ulcer submandibular region
M, male; F, female; SCC, squamous cell carcinoma; N/A, not available.
 T Baykul, HH Yilmaz, Ü Aydin et al.
Early diagnosis of oral cancer

FIGURE 1: Squamous cell carcinoma under the left posterior portion of the tongue in
the floor of the mouth in a patient who was a non-smoker. Lesions of this type cannot
be detected without a detailed clinical examination under adequate illumination

FIGURE 2: An oral lymphoma malignancy in the right maxilla

advanced clinical stage of the primary
tumours.38,85 All of the oral tumours are
asymptomatic in the early stages and may,
therefore, be in an advanced stage at
diagnosis, as for the 23 cases reported here.
These findings are in accordance with those
in the published elsewhere in the literature.
quality of life of patients with oral cancers,
healthcare providers should perform oral
cancer examinations as part of their patient
care regime, and should be knowledgeable
about the early signs of oral carcinoma. Oral
cancer awareness among the public should
also be improved.

Conclusion Conflicts of interest

To decrease the morbidity and mortality of The authors had no conflicts of interest to
oral cavity tumours and to improve the declare in relation to this article.

745
 T Baykul, HH Yilmaz, Ü Aydin et al.
Early diagnosis of oral cancer

FIGURE 3: Malignant melanoma in the left maxilla. Pigmentation and an ulcer can be
seen on the palatal aspect

• Received for publication 19 January 2010 • Accepted subject to revision 5 February 2010
• Revised accepted 6 April 2010
Copyright © 2010 Field House Publishing LLP

References carcinoma and oral precancerous conditions.

1 Parkin DM, Bray F, Ferlay J, et al: Global cancer
statistics, 2002. CA Cancer J Clin 2005; 55: 74 –
108.
2 Daley T, Darling M: Nonsquamous cell
malignant tumours of the oral cavity: an
overview. J Can Dent Assoc 2003; 69: 577 – 582.
3 Epstein JB, Zhang L, Rosin M: Advances in the
diagnosis of oral premalignant and malignant
lesions. J Can Dent Assoc 2002; 68: 617 – 621.
4 Vokes EE, Weichselbaum RR, Lippman SM, et al:
Head and neck cancer. N Engl J Med 1993; 328:
184 – 194.
5 Farah CS, McCullough MJ: Oral cancer
awareness for the general practitioner: new
approaches to patient care. Aust Dent J 2008;
53: 2 – 10.
6 Dolan RW, Waughan CW, Fuleihan N:
Symptoms in early head and neck cancer: an
inadequate indicator. Otolaryngol Head Neck
Surg 1998; 119: 463 – 467.
7 Gellrich NC, Suarez-Cunqueiro MM, Bremerich
A, et al: Characteristics of oral cancer in a
central European population: defining the
dentist’s role. J Am Dent Assoc 2003; 134: 307 –
314.
8 Erisen L, Basut O, Tezel I, et al: Regional
epidemiological features of lip, oral cavity, and
oropharyngeal cancer. J Environ Pathol Toxicol
Oncol 1996; 15: 225 – 229.
9 Reichart PA: Primary prevention of mouth
Mund Kiefer Gesichtschir 2000; 4: 357 – 364 [in
German].
10 Boffetta P, Ye W, Adami HO, et al: Risk of
cancers of the lung, head and neck in patients
hospitalized for alcoholism in Sweden. Br J
Cancer 2001; 85: 678 – 682.
11 Martin LM, Bouquot JE, Wingo PA, et al: Cancer
prevention in the dental practice: oral cancer
screening and tobacco cessation advice. J Public
Health Dent 1996; 56: 336 – 340.
12 Tomar SL: Dentistry’s role in tobacco control. J
Am Dent Assoc 2001; 132(suppl): 30S – 35S.
13 Shiboski CH, Shiboski SC, Silverman S Jr: Trends
in oral cancer rates in the United States, 1973 –
1996. Community Dent Oral Epidemiol 2000; 28:
249 – 256.
14 Johnson N: Tobacco use and oral cancer: a
global perspective. J Dent Educ 2001; 65: 328 –
339.
15 Hodge KM, Flynn MB, Drury T: Squamous cell
carcinoma of the upper aerodigestive tract in
nonusers of tobacco. Cancer 1985; 55: 1232 –
1235.
16 Rich AM, Radden BG: Squamous cell
carcinoma of the oral mucosa: a review of 244
cases in Australia. J Oral Pathol 1984; 13: 459 –
471.
17 Jovanovic A, Schulten EAJM, Kostense PJ, et al:
Tobacco and alcohol related to the anatomic
site of oral squamous cell carcinoma. J Oral

746
 T Baykul, HH Yilmaz, Ü Aydin et al.
Early diagnosis of oral cancer
Pathol Med 1993; 22: 459 – 462.
18 Sciubba JJ: Oral cancer: the importance of early
diagnosis and treatment. Am J Clin Dermatol
2001; 2: 239 – 251.
19 Franceschi S, Bidoli E, Herrero R, et al:
Comparison of cancers of the oral cavity and
pharynx worldwide: etiological clues. Oral
Oncol 2000; 36: 106 – 115.
20 Lewin F, Norell SE, Johansson H, et al: Smoking
tobacco, oral snuff, and alcohol in the etiology
of squamous cell carcinoma of the head and
neck: a population-based case-referent study in
Sweden. Cancer 1998; 82: 1367 – 1375.
21 Reibel J: Tobacco and oral diseases. Update on
the evidence, with recommendations. Med Princ
Pract 2003; 12(suppl 1): 22 – 32.
22 Llewellyn CD, Johnson NW, Warnakulasuriya
KA: Risk factors for squamous cell carcinoma of
the oral cavity in young people: a
comprehensive literature review. Oral Oncol
2001; 37: 401 – 418.
23 Singh B, Bhaya M, Zimbler M, et al: Impact of
co-morbidity on outcome of young patients
with head and neck squamous cell carcinoma.
Head Neck 1998; 20: 1 – 7.
24 Schantz SP, Yu GP: Head and neck cancer
incidence trends in young Americans, 1973 –
1997, with a special analysis for tongue cancer.
Arch Otolaryngol Head Neck Surg 2002; 128: 268
– 274.
25 Silverman S Jr, Gorsky M, Lozada F: Oral
leukoplakia and malign transformation: a
follow up study of 257 patients. Cancer 1984;
53: 563 – 568.
26 Robinson NP, Mickelson AR: Early diagnosis of
oral cavity cancers. Otolaryngol Clin North Am
2006; 39: 295 – 306.
27 Mashberg A, Feldman LJ: Clinical criteria for
identifying early oral and oropharyngeal
carcinoma: erythroplasia revisited. Am J Surg
1988; 152: 351 – 353.
28 Mashberg A, Merletti F, Boffetta P, et al:
Appearance, site of occurrence and physical
and clinical characteristics of oral carcinoma in
Torino, Italy. Cancer 1989; 63: 2522 – 2527.
29 Silverman S Jr (ed): Oral Cancer, 3rd edn.
Atlanta: American Cancer Society, 1990.
30 van der Meij EH, Mast H, van der Waal I: The
possible premalignant character of oral lichen
planus and oral lichenoid lesions: a prospective
five-year follow-up study of 192 patients. Oral
Oncol 2007; 43: 742 – 748.
31 Gillison ML, Koch WM, Capone RB, et al:
Evidence for a causal association between
human papillomavirus and a subset of head
and neck cancers. J Natl Cancer Inst 2000; 82:
709 – 720.
32 Gillison ML, Koch WM, Shah KV: Human
papillomavirus in head and neck squamous
cell carcinoma: are some head and neck
cancers a sexually transmitted disease? Curr
Opin Oncol 1999; 11: 191 – 199.
747
33 Franco EL, Kowalski LP, Oliveira BV, et al: Risk
factors for oral cancer in Brazil: a case–control
study. Int J Cancer 1989; 43: 992 – 1000.
34 Zheng TZ, Boyle P, Hu HF, et al: Dentition, oral
hygiene and risk of oral cancer: a case–control
study in Beijing, People’s Republic of China.
Cancer Causes Control 1990; 1: 235 – 241.
35 Lehew CW, Epstein JB, Kaste LM, et al: Assessing
oral cancer early detection: clarifying dentists’
practices. J Public Health Dent 2009; Sep 17
[epub ahead of print].
36 Silverman S Jr: Demographics and occurrence
of oral and pharyngeal cancers: the outcomes,
the trends, the challenge. J Am Dent Assoc 2001;
132(suppl): 7S – 11S.
37 Kademani D, Bell RB, Bagheri S, et al:
Prognostic factors in intraoral squamous cell
carcinoma: the influence of histologic grade. J
Oral Maxillofac Surg 2005; 63: 1599 – 1605.
38 Kademani D: Oral cancer. Mayo Clin Proc 2007;
82: 878 – 887.
39 Waldron CA, Shafer WG: Leukoplakia revisited:
a clinicopathologic study of 3256 oral
leukoplakias. Cancer 1975; 36: 1386 – 1392.
40 Scully C, Bagan JV, Hopper C, et al: Oral cancer:
current and future diagnostic techniques. Am J
Dent 2008; 21: 199 – 209.
41 Lees J: Incidence of weight loss in head and
neck cancer patients on commencing
radiotherapy treatment at a regional oncology
centre. Eur J Cancer Care 1999; 8: 133 – 136.
42 Epstein JB, Emerton S, Kolbinson DA, et al:
Quality of life and oral function following
radiotherapy for head and neck cancer. Head
Neck 1999; 21: 1 – 11.
43 Tomar SL, Logan HL: Florida adults’ oral cancer
knowledge and examination experiences. J
Public Health Dent 2005; 65: 221 – 230.
44 Cuffari L, de Siqueira JTT, Nemr K, et al: Pain
complaint as the first symptom of oral cancer:
a descriptive study. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 2006; 102: 56 – 61.
45 Neville BW, Day TA: Oral cancer and
precancerous lesions. CA Cancer J Clin 2002; 52:
195 – 215.
46 Evans SJ, Langdon JD, Rapidis AD, et al:
Prognosis and significance of STNMP and
velocity of tumour growth in oral cancer.
Cancer 1982; 49: 773 – 776.
47 Visser O, Coebergh JWW, Otter R, et al: Head
and neck tumours in The Netherlands 1989 –
1995. In: Netherlands Cancer Registry.
Eindhoven: Association of Comprehensive
Cancer Centers (IKZ), 1998; pp 12 – 28.
48 Williams RG: The early diagnosis of carcinoma
of the mouth. Ann R Coll Surg Engl 1981; 63: 423
– 425.
49 Ries LAG, Melbert D, Krapcho M, et al: SEER
Cancer Statistics Review, 1975 – 2004. Bethesda,
MD: National Cancer Institute, 2007.
50 Mashberg A, Samit AM: Early detection,
diagnosis, and management of oral and
 T Baykul, HH Yilmaz, Ü Aydin et al.
Early diagnosis of oral cancer
oropharyngeal cancer. CA Cancer J Clin 1989;
39: 67 – 88.
51 Gurney TA, Eisele DW, Orloff LA, et al:
Predictors of quality of life after treatment for
oral cavity and oropharyngeal carcinoma.
Otolaryngol Head Neck Surg 2008; 129: 262 –
267.
52 Scott SE, Grunfeld EA, Main J, et al: Patient
delay in oral cancer: a qualitative study of
patients’ experiences. Psychooncology 2006; 15:
474 – 485.
53 Gómez I, Seoane J, Varela-Centelles P, et al: Is
diagnostic delay related to advanced-stage oral
cancer? A meta-analysis. Eur J Oral Sci 2009;
117: 541 – 546.
54 Allison P, Locker D, Feine JS: The role of
diagnostic delays in the prognosis of oral
cancer: a review of the literature. Oral Oncol
1998; 34: 161 – 170.
55 Horowitz AM, Canto MT, Child WL: Maryland
adults’ perspectives on oral cancer prevention
and early detection. J Am Dent Assoc 2002; 133:
1058 – 1063.
56 Petti S, Scully C: Oral cancer knowledge and
awareness: primary and secondary effects of an
information leaflet. Oral Oncol 2007; 43: 408 –
415.
57 McLeod NM, Saeed NR, Ali EA: Oral cancer:
delays in referral and diagnosis persist. Br Dent
J 2005; 198: 681 – 684.
58 Schnetler JF: Oral cancer diagnosis and delays
in referral. Br J Oral Maxillofac Surg 1992; 30:
210 – 213.
59 Kujan O, Duxbury AJ, Glenny AM, et al:
Opinions and attitudes of the UK’s GDPs and
specialists in oral surgery, oral medicine and
surgical dentistry on oral cancer screening. Oral
Dis 2006; 12: 194 – 199.
60 Bruun JP: Time elapse by diagnosis of oral
cancer. Oral Surg Oral Med Oral Pathol 1976; 42:
139 – 149.
61 Guggenheimer J, Verbın RS, Johnson JT, et al:
Factors delaying the diagnosis of oral and
oropharyngeal carcinomas. Cancer 1989; 64:
932 – 935.
62 Brouha XD, Tromp DM, Koole R, et al:
Professional delay in head and neck cancer
patients: analysis of the diagnostic pathway.
Oral Oncol 2007; 43: 551 – 556.
63 Holmes JD, Dierks EJ, Homer LD, et al: Is
detection of oral and oropharyngeal squamous
cancer by a dental health care provider
associated with a lower stage at diagnosis? J
Oral Maxillofac Surg 2003; 61: 285 – 291.
64 Kowalski LP, Franco EL, Torloni H, et al:
Lateness of diagnosis of oral and
oropharyngeal carcinoma: factors related to
the tumour, the patient and health
professionals. Eur J Cancer B Oral Oncol 1994;
30B: 167 – 173.
65 McCann MF, Macpherson LM, Binnie VI, et al:
A survey of Scottish primary care dental
748
practitioners’ oral cancer-related practices and
training requirements. Community Dent Health
2000; 17: 24 – 30.
66 Hahn W: Clinical signs for the early recognition
of cancer of the oral cavity. Int Dent J 1977; 27:
165 – 171.
67 Guggenheimer J, Weissfeld JL, Kroboth FJ: Who
has the opportunity to screen for oral cancer?
Cancer Causes Control 1993; 4: 63 – 66.
68 Choido GT, Eigner T, Rosenstein DI: Oral cancer
detection. The importance of routine screening
for prolongation of survival. Postgrad Med 1986;
80: 231 – 236.
69 Winn DM, Sandberg AL, Horowitz AM, et al:
Reducing the burden of oral and pharyngeal
cancers. J Calif Dent Assoc 1998; 26: 445 – 451,
454.
70 Jullien JA, Downer MC, Zakrzewska JM, et al:
Evaluation of a screening test for the early
detection of oral cancer and precancer.
Community Dent Health 1995; 12: 3 – 7.
71 Kowalski LP, Carvalho AL: Influence of time
delay and clinical upstaging in the prognosis of
head and neck cancer. Oral Oncol 2001; 37: 94
– 98.
72 Zavras A, Andreopoulos N, Katsikeris N, et al:
Oral cancer treatment costs in Greece and effect
of advanced disease. BMC Public Health 2002; 2:
12.
73 Garzino-Demo P, Dell’Acqua A, Dalmasso P, et
al: Clinicopathological parameters and
outcome of 245 patients operated for oral
squamous cell carcinoma. J Craniomaxillofac
Surg 2006; 34: 344 – 350.
74 McDowell JD: An overview of epidemiology
and common risk factors for oral squamous cell
carcinoma. Otolaryngol Clin North Am 2006; 39:
277 – 294.
75 Shafer WG: Initial mismanagement and delay
in diagnosis of oral cancer. J Am Dent Assoc
1975; 90: 1262 – 1264.
76 Carvalho AL, Pintos J, Schlecht NF, et al:
Predictive factors for diagnosis of advanced-
stage squamous cell carcinoma of the head and
neck. Arch Otolaryngol Head Neck Surg 2002;
128: 313 – 318.
77 Teppo H, Koivunen P, Hyrynkangas K, et al:
Diagnostic delays in laryngeal carcinoma:
professional diagnostic delay is a strong
independent predictor of survival. Head Neck
2003; 25: 389 – 394.
78 Ho T, Zahurak M, Koch WM: Prognostic
significance of presentation-to-diagnosis
interval in patients with oropharyngeal
carcinoma. Arch Otolaryngol Head Neck Surg
2004; 130: 45 – 51.
79 Kerdpon D, Sriplung H: Factors related to delay
in diagnosis of oral squamous cell carcinoma
in southern Thailand. Oral Oncol 2001; 37: 127
– 131.
80 Onizawa K, Nishihara K, Yamagata K, et al:
Factors associated with diagnostic delay of oral
 T Baykul, HH Yilmaz, Ü Aydin et al.
Early diagnosis of oral cancer

squamous cell carcinoma. Oral Oncol 2003; 39:
781 – 788.
81 Wildt J, Bundgaard T, Bentzen SM: Delay in the
diagnosis of oral squamous cell carcinoma. Clin
Otolaryngol Allied Sci 1995; 20: 21 – 25.
82 Symonds P, Bolger B, Hole D, et al: Advanced
stage cervix cancer: rapid tumour growth
rather than late diagnosis. Br J Cancer 2000; 83:
566 – 568.
83 Symonds RP: Cancer biology may be important
than diagnostic delay. BMJ 2002; 325: 774.
84 Epstein JB, Epstein JD, Le ND, et al:
Characteristics of oral and paraoral malignant
lymphoma: a population-based review of 361
cases. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod 2001; 92: 519 – 525.
85 Zini A, Czerninski R, Sgan-Cohen HD: Oral
cancer over four decades: epidemiology, trends,
histology and survival by anatomical sites. J
Oral Pathol Med 2009; Dec 16 [Epub ahead of
print].
86 Neville BW, Day TA: Oral cancer and
precancerous lesions. CA Cancer J Clin 2002; 52:
195 – 215.

Author’s address for correspondence

Associate Professor Timuçin Baykul
.
Istiklal Mah. 1101.sok. No. 26/6, Isparta, Turkey.
E-mail: timucinbaykul@yahoo.com

749