ORL 2001;63:217–221
Distant Metastases from Lip and
Oral Cavity Cancer
Jan Betka
Department of Otolaryngology – Head and Neck Surgery, Charles University, Prague, Czech Republic
Key Words
Distant metastases W Lip cancer W Oral cancer
Abstract
Distant metastases related to lip carcinomas occur very
exceptionally (0.5–2%) and can be expected in cases of
advanced tumors with advanced regional disease. Dis-
tant metastases from oral cavity carcinomas variy over a
broad interval (8–17%) and depend also on the stage of
disease. The knowledge of the presence of distant me-
tastases is vital for the planning of further treatment.
From a clinical point of view, patients with lip and oral
cavity can be divided into a group where the risk of dis-
tant metastases is low, and into a high-risk one. In low-
risk group patients (stages I, II and III) the risk of the inci-
dence of distant metastases is 3%, and the diagnostic
approach should consist of an X-ray of the lungs and liv-
er tests. Further examinations are necessary if there are
symptoms suggesting the presence of distant metas-
tases or previous examinations are abnormal. The high-
risk group (stage IV) and all patients with locoregional
relapse have a risk of distant metastases of approximate-
ly 10% and the best treatment consists of a positron
emission tomography (PET) scan. If a PET scanner is not
available it is recommended to run a computed tomogra-
phy scan of the lungs and liver tests. If any clinical inves-
tigation is abnormal further tests are necessary.
Copyright © 2001 S. Karger AG, Basel
© 2001 S. Karger AG, Basel
ABC 0301–1569/01/0634–0217$17.50/0
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According to the American Cancer Society, about
1,220,100 new cancer cases were expected to be diag-
nosed in 2000 (1.3 million cases of basal and squamous
cell skin cancers are not included). Some 30,200 patients
were expected to contract oral cavity and pharynx in 2000
and it was estimated that 7,800 would die from tumor
that year. Lip and oral cavity carcinoma is fortunately rel-
atively rare [1].
Lip Cancer
In the United States, lip carcinomas account for just
12% of tumors found in the head and neck area, and the
number of male patients is 6 times as high as that of
females. The highest incidence rate of lip carcinomas is in
South Africa (13.3 cases/100,000 inhabitants) and Spain
(11.4/100,000 inhabitants). As to females, it is Thailand
which shows the highest incidence rate (3.8/100,000 in-
habitants). From a histological viewpoint, these carcino-
mas are almost invariably of a squamous or basal cell
type. Distant metastases related to lip carcinomas occur
very exceptionally. As a rule, this is attributable to a gen-
erally early diagnosis of the tumor which, because of its
good accessibility, is identified in initial stages in 93% of
cases [2]. As to regional metastases, they occur in 5–7% of
cases, and are thus relatively rare. Distant metastases are
exceptional (0.5–2%) and can be expected in cases of
Postgraduate Institute of Med. Education and Research
Jan Betka, MD, PhD
Department of Otolaryngology – Head and Neck Surgery
I. Medical Faculty Charles University, University Hospital Motol
Vúvalu 84, CZ–150 06 Motol-5, Prague (Czech Republic)
Fax +420 2 290 495, E-Mail jan.betka@lfmotol.cuni.cz
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Table 1. Incidence rates of distant metastases
Kotwall Peltier O’Brien
et al. [6] et al. [7] et al. [8]
Patients 832 200 153
FU duration Autopsy Autopsy Autopsy
Total number of oral
cavity cases, %
Oral cavity bottom, % 43 23
Tongue, % 49 33 27
Others, % 32 13 33
advanced tumors with advanced regional nodal disease
[3]. The global trend is one of a decreasing incidence rate
of lip carcinomas.
Oral Cancer
In the United States, oral cavity carcinomas account
for 7% of diagnosed head and neck tumors. The incidence
rate is twice as high for males as for females, and it is
assumed that the number of oral cavity carcinoma cases is
higher in the old-age population. There are significant dif-
ferences in the oral cavity carcinoma incidence rates from
one country to another, the top countries in this respect
being Bermuda (incidence rate 16.3/100,000 ) and India.
As to Europe, the highest incidence rate among males is in
France (incidence rate 13.5/100,000) while the opposite
end belongs to Japanese females (incidence rate 0.13/
100,000). Squamous cell carcinomas (SCCs) account for
more than 90% of oral cavity tumors. Other oral cavity
tumors are represented by those of small salivary glands,
of which the adenoid cystic carcinoma is the most fre-
quent type (it accounts for 42% of tumors affecting small
salivary glands, but less than 1% of all head and neck
tumors). The adenoid cystic carcinoma exhibits a tenden-
cy toward producing distant metastases (up to 58.8%). In
rare instances, nonepithelial tumors can be found as well,
namely soft tissue sarcomas (incidence rate 1/100,000)
and Kaposi's sarcoma (50% of patients with AIDS devel-
op Kaposi's sarcomas in the oral cavity). Malignant mela-
nomas are found more frequently among Blacks and Japa-
nese; some 0.2–0.8% of these tumors are found in the oral
cavity. Cases of lymphomas located in the oral cavity are
extremely rare (0.2%).
The first to note the possibility of distant metastases
associated with head and neck carcinomas was Crile [4].
In his study in which he presented the results of his analy-
218 ORL 2001;63:217–221
Braund and Burke Zbären and Probert Merino Brennan
Martin [9] [10] Lehmann [11] et al. [12] et al. [13] et al. [14]
284 88 101 779 5,019 769
Autopsy Autopsy Autopsy 5 years 2 years 2 years
40 32 14 8
6 17
25 15
36 17
sis of autopsy findings, he found distant metastases relat-
ed to oral cavity carcinomas only exceptionally. Most of
the patients died of a locoregional relapse or because of
the tumor persistence. Shaha et al. [5] mention a 13%
incidence rate of distant metastases related to carcinomas
of the oral cavity tumors in their study of a group of 320
patients. They view the advancement of the disease and
relapses of the primary process or metastases as the most
important risk factors. It is interesting to note that inci-
dence rates of distant metastases based on both autopsy
documents and clinical studies vary over a broad interval,
ranging between 6 and 43% in the autopsy case and 8 and
17% in clinical studies (table 1) [6–14].
Relation between the Primary Tumor Extent
and the Incidence Rate of Distant Metastases
Most authors present evidence corroborating the exis-
tence of a relation between the advancement of the prima-
ry process and the incidence rate of distant metastases
[15]. They submit proof indicating that the larger or more
advanced the primary process is, the higher the probabili-
ty of occurrences of distant metastases (tables 2, 3) [6, 13,
16–19]. As to advanced tumor development stages, rele-
vant publications mention incidence rates of distant me-
tastases ranging between 20 and 40%.
Relation between the Condition of Regional
Lymphatic Node Metastases and the Incidence
Rate of Distant Metastases
There is a great deal of evidence that there exists a cor-
relation between the extent of lymph node metastases
involvement and incidence rate of distant metastases. It is
interesting to note that autopsy studies present higher
Postgraduate Institute of Med. Education and Research
Betka
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Table 2. Disease stage versus the incidence of distant metastases Table 3. Primary tumor size versus the incidence rate (%) of distant
metastases
Merino et al. [13] Kotwall et al. [6] Vikram et al. [16]
(clinical study) (autopsy study) (clinical study) Merino Berger and Loree and Cerezo
et al. [13] Fletcher [17] Strong [18] et al. [19]
Stage I 2 42
Stage II 6 35 T1 5 25 15 35
Stage III 9 43 20 T2 10 20 27 37
Stage IV 20 55 T3 13 23 31 23
T4 16 30 40 38
p ! 0.05 NS p ! 0.05 NS

Table 4. Incidence rates (%) of distant metastases for different N-stages

Merino Berger and Vikram Arons and Loree and Kotwall Zbären and
et al. [13] Fletcher [17] et al. [16] Smith [22] Strong [18] et al. [6] Lehmann [11]
(autopsy) (autopsy)

N0 5 9 4 12 3 (I, II) 42 24
4 (III, IV)
N1 12 17 18 34 (N1–N2)
N2 22 26 (2a) 25 (N1–N3) 28 (N1–N3) 24 (N1–N3) 40 (N2–N3)
23 (2b)
N3 27 38 (3a) 54
33 (3b)

incidence rates than clinical studies [20, 21]. This may be Table 5. Localization of distant metastases (%)
attributable to the former studies being focused on pa-
Autopsy study Clinical study
tients with a negative prognosis; however, it is also possi-
[6–9, 11, 29–31] [12, 13, 16, 32–35]
ble that a process of hematogenous spread and the forma-
tion of metastases precedes the formation of regional Lung 71 54
metastases (table 4) [6, 11, 13, 16–18, 22]. Some authors Liver 36 10
view the effect of extracapsular spread is the most impor- Bones 15 22
Mediastinum 23 3.4
tant prediction factor, along with the existence of more
Distant nodes 16 Sporadic
than four positive lymph node metastases [23–26]. Suprarenal glands 14 Sporadic
Kidney 14 Sporadic
Heart 13 Sporadic
Distant Metastases – Incidence and Brain 12 Sporadic
Localization

The incidence of distant metastases at the time of diag-

nosis varies from 2 to 17% of patients with head and neck
SCC [27, 28]. Distant metastases from oral cavity tumors
can be expected on the lower end of this scale. Distant
metastases most frequently attack lungs (54%), as well as
bones and liver, etc. (table 5) [6–9, 11–13, 16, 29–35].
According to autopsy studies and clinical studies, there
exists a 2–3 times higher incidence in autopsy.
Clinical Management
Lip tumors very rarely produce distant metastases.
Oral cavity tumors exhibit a relatively low tendency
toward creating distant metastases. The probability of the
formation of a distant metastasis depends on: (1) histolog-
ical composition of the tumor; (2) extent of the primary
Postgraduate Institute of Med. Education and Research

Lip and Oral Cavity Cancer ORL 2001;63:217–221 219

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Table 6. Diagnostics and treatment of distant metastases

Location of metastases Clinical symptoms Examination methods Treatment Forecast

Lungs – solitary, Asymptomatic cough,
multiple pain, hemoptysis, difficult
breathing, weight loss
Bones – the most Aches, especially at night,
frequently affected ones ebbing when the patient
include the femur, moves, pathological frac-
pelvis, spine, ribs tures
Liver Hepatomegaly. Pains in
the liver area, hepatitis,
fever, weight loss
Brain Headaches, nausea,
neurological symptoms,
psychical changes
Lung X-ray (capable of identifying only
metastases 11 cm); a vague finding is an
indication for an additional CT or MRI
examination; the sensitivity of the cyto-
logical analysis of sputum is just 5–20%.
Bronchoscopy needed to eliminate the
possibility of duplication
Increased ALP (bone isoenzyme) Bone
X-ray (50% sensitivity). Radionuclide
scanning of the skeleton (80–95% sensi-
tivity). CT, MRI examination
Increased liver and ALP tests. Ultrasonic
scanning (80% sensitivity). CT and MRI
examination (90% sensitivity) CT +
arterial portography (95% sensitivity).
Biopsy needed to eliminate the possibility
of duplication
Contrast CT, contrast MRI, brain
angiography
Surgical wedge resection
(subject to the patient being
in a good shape and having
good lung functions, and to
the metastases being surgi-
cally accessible). Palliative
radiotherapy if the bronchus
is obstructed
Palliative
Exceptionally a resection of
metastases. Palliative
Treatment of solitary
metastases using the Leksell
gammaknife, exceptionally
surgical exstirpation.
Multiple metastases – palliative
The surgical removal is
possible for just 5–15% of
patients, of whom 30%
survive more than 5 years
after the operation.
Otherwise, the prognosis
is unfavorable
Unfavorable
Unfavorable
Unfavorable

tumor; (3) extent of regional lymphatic nodes disease, and
(4) locoregional persistence or relapse.
The knowledge of the presence of distant metastases is
vital for the planning of further treatment. From a clinical
viewpoint, patients suffering from a lip or oral cavity car-
cinoma can be divided into a group where the risk of the
incidence of distant metastases is low, and into a high-risk
one. As to the latter group, it comprises patients having a
T4 tumor and/or manifesting N2b–N3 regional nodes (i.e.
those falling into stage IV), and all patients showing a
locoregional relapse. Insofar as the low-risk patients are
concerned, the risk of the incidence of distant metastases
at the time the primary process is diagnosed is between 2
and 3%; consequently, the treatment should consist in an
X-ray of the lungs and liver tests rather than in an exagger-
ated diagnostic tracking of distant metastases. Further
examinations are necessary if there are symptoms suggest-
ing the presence of distant metastases and/or if the results
of previous examinations are abnormal. As to FU, it is
recommended to take a lung X-ray once a year and to con-
duct clinical checks.
As to the high-risk patients, the risk of the incidence of
distant metastases is approximately 10%. The riskiest
group of patients comprises those diagnosed for an N3
lymphatic node condition or suffering from a locoregional
relapse.
Although there exists a higher risk of the formation of a
distant metastasis in this group of patients, an extensive
screening is neither generally recommended, nor econom-
ically efficient. With the disease in an advanced stage, the
best current treatment consists in a positron emission
tomography (PET) scan and/or in targeted examinations
(table 6). Insofar as locoregional relapses are concerned,
when an extensive surgery is planned, it is recommended
to run a PET scan which will can give us early information
of a distant metastasis, thus sparing us a disappointment
after a demanding operation. However, distant metas-
tases can also appear as a result of clinical manifestations
of micrometastases. If a PET scanner is not routinely
available, it is necessary to run a computed tomography
scan of the lungs. Further examinations depend on the
clinical finding of the patient. As to FU, it is recom-
mended to take a lung X-ray twice a year and to repeat
liver tests once a year. The monitoring of the two groups
of patients referred to above spans their whole lifetime,
not just because of a risk of a local or distant relapse of the
disease, but also due to a threat of a tumor duplication.
Postgraduate Institute of Med. Education and Research

220 ORL 2001;63:217–221 Betka

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