ORIGINAL ARTICLE

Squamous cell carcinoma of the oral tongue in patients

younger than 30 years: clinicopathologic features and
outcome
Soudry, E.,*, Preis, M.,*, Hod, R.,* Hamzany, Y.,*, Hadar, T.,*, Bahar, G.,*, Strenov, Y.
& Shpitzer, T.*,
*Department of Otolaryngology-Head and Neck Surgery, Rabin Medical Center, Petah Tiqwa, Sackler School of
Medicine, Tel Aviv University, Tel Aviv, and Department of Pathology, Rabin Medical Center, Petah Tiqwa,
Israel
Accepted for publication 2 June 2010
Clin. Otolaryngol. 2010, 35, 307312

Objective: To assess the possible effect of young age on

clinical behaviour and survival outcome of squamous cell
carcinoma of the oral tongue.
Design: Retrospective, case control study.
Setting: A major tertiary referral centre.
Participants: Eighty-five patients with oral tongue
squamous cell carcinoma with at least 2 years of follow-up.
Main outcome measurements: Clinical and histopathological staging, disease-free survival, disease-specific
survival and overall survival.
Results: Eleven patients (13%) were younger than
30 years. Compared to the older patients, they had a
significantly worse N stage (P = 0.041), more perineural

invasion (P = 0.012), and higher rates, though not significant, of treatment failure (46%, including 60% with
distant metastases, versus 35%, nearly all locoregional)
and mortality (100% of treatment failures versus 73%).
There were no significant between-group differences in
5-year disease-free, disease-specific, and overall survival.
Conclusion: In this study, patients younger than
30 years of age presented with advanced tumour stages
and with a different failure pattern compared to the older
age group. This may be attributable to age-related
biologic behaviour or delayed cancer diagnosis. Differences in disease free survival and overall survival could
not be established.

Squamous cell carcinoma (SCC) of the oral tongue

accounts for approximately 30% of oral cavity SCCs and
is thus one of the most frequent head and neck cancers.1,2
Crude Incidence is on average between 10 and 20 cases
per 100 000 in Europe and the USA.3 Differing patterns
emerge when oral cancer incidence trends are analysed by
age groups. Rising trends of oral cancer in the young and
middle aged (under 50 years old), particularly cancer of
the tongue, have been observed in European countries.2
In USA, despite the decreasing incidence of head and
neck cancer, there is a significant increase in the incidence of squamous cell carcinoma (SCC) of the oral tongue, base of tongue and tonsils in young white patients
aged 3044 years.1 Differences in cancer pathogenesis and
genetic alterations have been studied as possible causes
for cancer in the young aged group.

Prognostication and treatment decisions are currently

based on TNM staging and presence of perineural and
perivascular invasion on histopathological study. Age is
not considered a prognostic factor.
Most of the studies conducted to date on the potential prognostic significance of age in tongue cancer have
yielded conflicting results.417 This might be explained
by the almost exclusive use of 4045 years as the cutoff for comparison, with a wide range of mean ages,
from 30 to 38 years. Yet it is possible that the younger-than-40- to 45-year group is itself composed of heterogeneous subgroups and that lowering the cut-off
would yield a more homogenous sample. Only two
studies have evaluated oral tongue SCC in patients
younger than 30 years,16,17 and both were done nearly
30 years ago, when the treatment approach was considerably different.
The aim of the present study was to evaluate the clinical
and histopathological parameters and survival outcomes of
oral tongue SCC in patients younger than 30 years of age
compared to older patients.

Correspondence: T. Shpitzer, MD, Department of Otolaryngology Head

and Neck Surgery, Rabin Medical Center, Beilinson Campus, Petah Tiqwa 49100, Israel. Tel.: 972-3-937 6456; fax: 972-3-937 6467;
e-mail: thomas-s@zahav.net.il
 2010 Blackwell Publishing Ltd Clinical Otolaryngology 35, 307312

307

308 E. Soudry et al.

Patients and methods

Ethical considerations

This is a retrospective chart review, and prior to the

study, permission was obtained from the local institutional review board to review the patients medical charts,
histopathological reports and follow up data.
Patients

The study was conducted in a tertiary university-affiliated

medical centre. The medical files of all patients who were
treated for tongue cancer in our department from 1992
to 2007 and followed for a minimum of 2 years, were
reviewed. Only patients with histologically-proven pure
oral tongue squamous cell carcinoma were included.
Demographic background, habits, clinicopathological
parameters (clinical stage, and histopathologic features),
treatment (surgical procedure, postoperative treatment)
and survival outcomes were documented, and the findings were compared between patients younger than
30 years and older patients.
Statistical analysis

Continuous variables are expressed as mean standard

deviation (sd) and categorical variables as percentages.
Differences in mean continuous variables between groups
were analysed by Student t-test, and differences in categorical variables, by chi-square test or Fisher exact test.
Disease-specific survival (DSS) rate and disease-free survival (DFS), defined by the interval between the date of
diagnosis and the day of death or recurrence or the last
follow-up, were calculated by the Kaplan-Meier method;
log-rank test were used for univariate analysis to compare
DSS and DFS between the groups.
Multivariate analysis was performed using the Cox proportional hazards model, in which DSS or DFS was the
dependent variable and, age, gender, pathological grade,
T stage classification (T1 versus T2 + T3), N stage (N0
versus N1 + N2) and perineural invasion (yes versus no)
were independent variables. A P-value of less than 0.05
was considered statistically significant. For statistical analyses, we used SPSS, version 15.0.1 software (SPSS, Chicago, IL, USA).
Results

Eighty-five patients met the study criteria. They included

39 male and 46 female patients of mean age
60.8 20.5 years (Fig. 1 age histogram). Eleven patients

Fig. 1. Age histogram.

(13%) were younger than 30 years and 74 were older,

including 10 who were aged 3045 years. Average age at
presentation was 24.1 4.9 years (range 1529) in the
younger group and 66.2 15.7 years (range 3294) in
the older group.
A history of smoking was positive in one patient (9%)
in the younger group and 20 patients (27%) in the older
group. Excessive alcohol intake was very rare in both
groups of patients, which is in accordance with the overall low alcohol intake in our country.18
The clinical and histopathological characteristics of the
patient groups are shown in Tables 1 and 2. Compared
to the older group, the younger patients had a significantly worse clinical radiological N stage (P = 0.041) in
presentation and more evidence of perineural invasion
(P = 0.012) on histopathological examination. There were
no significant between-group differences in histological
grade, tumour depth, or presence of lymph node extracapsular extension.
Treatment consisted of resection of the tongue tumour
in all cases. All but four patients also underwent elective
or therapeutic neck dissection, all of whom had small
tumours and were considered a very high operative risk.
Radial forearm free flap reconstruction of the tongue
defect was performed in 21 (25%) patients of whom 4
were younger than 30 years. Close (<5 mm) or involved
resection margins were observed on final histopathological analysis in three of the young patients (27%) and 13
of the older group (18%). Postoperative radiation or
chemoradiation was administered for advanced tumours
 2010 Blackwell Publishing Ltd Clinical Otolaryngology 35, 307312

Oral tongue SCC in under-30 age group

Table 1. Clinical characteristics

30 years and older patients

Females
Males
T stage
T1
T2
T3
T4
N stage
N0
N1
N2
N3
AJCC stage
III
IIIIV

of

patients

younger

than

Age < 30 years, n = 11

Age > 30 years,

n = 74

Number

Number

P-value

5
6

45
55

41
33

55
45

N.S.

5
4
2
0

46
36
18

38
30
5
1

51
41
7
1

N.S.

5
2
4
0

46
18
36

54
13
7
0

72
18
10

0.041

3
8

27
73

51
23

70
30

0.011

309

Treatment failure (Table 3) was documented in five

patients in the younger group (46%), including three
(60%) with distant metastases, one with local failure, and
one with regional failure. Average time to failure was
14.5 months; all five patients ultimately died of their disease. In the older group, 27 patients (36%) failed treatment, of whom 25 had a locoregional recurrence and two
had distant metastases. Average time to failure was
12.7 months; 20 patients (74%) ultimately died of their
disease. A second primary tumour of the head and neck
developed in five patients, all in the older group, which
led to a total failure in 32 (43%) patients in the older
group.
Disease specific and disease free survival

AJCC, American Joint Committee on Cancer; N.S., not significant.

and those with close or involved margins by standard

protocols. The treatment field included the tongue and
ipsilateral neck. For patients with N2, the contralateral
necks were treated. Radiation dose ranged between 54 Gy
and 60 Gy in most cases, and for positive margins,
between 60 Gy and 66 Gy. Treatment was planned in
most cases in three dimensional planes using 6 MV photons. Patients with very high risk features, such as positive margins massive extracapsular extension were treated
with concomitant chemoradiation (either cisplatin or cisplatin and 5-FU).

The mean duration of follow-up for the 85 patients was

4.6 years (range 4 months to 13.5 years). The 5-year DFS
rate was 55% in the younger group and 63% in the older
group (Fig. 2). Corresponding rates for 5-year diseasespecific survival (DSS) were 55% and 73% (Fig. 3), and
for 5-year overall survival, 55% and 61%. None of these
between-group differences was statistically significant.
The 5-year DSS and DFS according to age, gender,
pathological grade, T stage classification (T1 versus
T2 + T3), N stage (N0 versus N1 + N2) and perineural
invasion (yes versus no) in 85 patients with tongue carcinoma were analysed as well. In DSS univariate analysis
pathological grade, T stage classification (T1 versus
T2 + T3), N stage (N0 versus N1 + N2) and perineural
invasion (yes versus no) were significant (P = 0.015,
P = 0.006, P = 0.002 and P = 0.006, respectively). DFS
univariate analysis revealed that only (T1 versus T2 + T3)
was significant (P = 0.001).

Table 2. Histopathological characteristics of patients younger than 30 years and older patients
Age < 30 years,
n = 11

Pathological stage III

Pathological stage IIIIV
Histology
Well differentiated
Moderately differentiated
Poorly differentiated
Mean tumour thickness sd (mm)
Perineural invasion
Number of metastatic lymph nodes (average sd)
Extracapsular extension
N.S., not significant.
 2010 Blackwell Publishing Ltd Clinical Otolaryngology 35, 307312

Age > 30 years,

n = 74

Number

Number

P-value

3
8

27
73

51
23

69
31

0.011

2
8
1
9.4 5.4
5
2.4 2.7
2

18
73
9

30
27
11
7.8 5.2
9
0.9 2.3
6

44
40
16

N.S.

50
20

13
9

N.S.
0.012
0.004
N.S.

310 E. Soudry et al.

Table 3. Analysis of failures in patients younger than 30 years

and older patients

Failure
Local
Regional
Loco-regional
Distant
Second primary
Total failures

Age < 30 years,

n = 11

Age > 30 years,

n = 74

Number

Number

5
1
1
0
3
0
5

46
20
20

27
8
13
4
2
5
32

36
30
48
15
4

60
46

43

Fig. 3. Disease-specific survival

30 years and older patients.

for

patients

younger

than

patients younger than 30 years and female patients, comprised a much larger fraction (13% and 54%, respectively) of the study group than expected according to the
literature. It is possible that our study group as a whole
differed from previously reported groups in that most of
the patients lacked the traditional risk factors of smoking
and alcohol intake. Thus, the tongue carcinoma in our
sample may have had a different epidemiology. This
question requires further investigation.
Fig. 2. Disease-free survival curves for patients younger than
30 years and older patients.

Multivariate Cox proporttional hazard model revealed

that only T stage was statistically significant predictor of
a reduced DFS (hazard ratio 4.45; 95% CI 1.8910.50,
P = 0.001) and T stage and lymph node involvement
were statistically significant predictor of a reduced DSS
(hazard ratio 3.24; 95% CI 1.318.02, P = 0.011 and hazard ratio 2.81; 95% CI 1.236.42, P = 0.014, respectively).
In both univariate and multivariate analysis, age was
not associated with DSS or DFS.
Discussion

In the literature, the reported median age at diagnosis of

cancer of the oral tongue is of 61 years and that approximately 9% of patients are diagnosed before age of
45 years, and 2%, before age 35 years, and that the overall 5-year relative survival is 60%.1 In the present study,

Strengths of the study

Studies of the possible prognostic significance of age on

the clinical course of oral tongue SCC reported conflicting results.417 The present study focused on the clinical
and pathological findings and outcome of 11 patients less
than 30 years old (average 24 years) with oral tongue
SCC. All underwent primary surgical resection of the tongue tumour and neck dissection, either electively or therapeutically. Postoperative radiation or chemoradiation
was administered for advanced tumours by standard protocols. This study is distinct from earlier reports because
of the younger age of the patients (<30 years versus 40
45 years) and the uniform treatment administered.
We are aware that due to the limited sample size, solid
evidence-based conclusions can not be made. Nonetheless, it should be remembered that SCC of the oral tongue is relatively rare in the young adult population and
thus reaching a large homogenous group of patients is
difficult, especially in the younger than 30-year-old
group. Studies featuring large groups of young patients
 2010 Blackwell Publishing Ltd Clinical Otolaryngology 35, 307312

Oral tongue SCC in under-30 age group

were based on literature reviews. Moreover, any evidence

that can shed light on this unique group of patients is of
value.
Comparison with other studies

In a literature review of published cases of patients younger than 40 years with tongue carcinoma (n = 122), Pitman et al.4 found a similar outcome to patients older
than 40 years, in agreement with several studies.57 Others, however, noted better disease-free and overall survival
in young adults than in older ones,810 whereas Friedlander et al.11 described worse disease-free survival in
patients younger than 40 years, with no difference from
older patients in overall survival.9 Sarkaria and Harari,12
in another literature review of 152 patients younger than
40 years with tongue cancer, the failure rate was 57% and
the death rate, 47%. The authors concluded that younger
adults have a worse prognosis than older ones. These
findings were in line with a 2007 study wherein diseasefree and overall survival were lower in the under-40-year
age group (n = 46) than the older group,13 and an earlier
study using a 45-year cut-off.14 A previous study from
our department showed that, in general, patients younger
than 45 years have the same outcome as older patients.
However, within the younger group, we noted two distinct disease patterns: an extremely aggressive course with
a high mortality rate within 2 years, and a more indolent
course with a lower mortality rate.15
Only two studies evaluated oral tongue cancer in
patients less than 30 years old (average age 23). Byers16
investigated the clinical course of 11 patients treated and
following during 19561973. Seven (64%) had stage 34
disease at presentation. The patients were treated by various modalities, with an overall survival of 45%. The second study was conducted by Newman et al.17 in 1983
and included 13 patients, 46% with stage 34 disease at
presentation, who underwent various initial treatments.
Eight patients died of disease (62%). The authors concluded that the under-30 age group had a similar prognosis by stage to older patients.
The younger patients in our cohort had a higher N
stage than the older patients and therefore a more
advanced tumour stage (73% stage 34), in agreement
with the high proportion of advanced tumours in the
younger groups of Byers16 and Newman et al.17 This finding has two potential explanations: a delay in diagnosis
owing to a lower index of clinical suspicion of tongue
SCC in younger patients or a more aggressive age-related
biologic behaviour of the tumour. The latter assumption
is supported by the significantly higher rate of perineural
invasion on histopathological examination in our younger
 2010 Blackwell Publishing Ltd Clinical Otolaryngology 35, 307312

311

group. Perineural invasion has been shown to be associated with a high risk of regional metastases, local recurrence, and decreased survival.19,20 At the same time,
second head and neck primary tumours developed only
in the older patients in our study. Together, these results
suggest that tumour biology may be age-related.
Analysis of other clinical or histopathological parameters yielded no significant differences between the age
groups perhaps because of the small sample size.
On univariate and multivariate analysis, age was not
associated with DFS and DSS. Only T stage was associated with DFS; T stage and N stage were associated on
multivariate analysis with DSS. The differences in diseasespecific and overall survival were not statistically significant between the two patient groups. In addition, there
was no between-group difference in the rate of treatment
failure in our study. However, each group exhibited a distinct pattern of failure. Most of the younger patients had
a distant recurrence (60%), and all died of the disease,
whereas most of the older patients failed locoregionally
(93%), and only 74% ultimately died of their disease. The
percentage of distant failure in the younger group is considerably higher than the 38% rate of distant failure in
SCC reported in previous studies.414 This finding, too,
raises the question of a different cancer pathogenesis and
tumour biology in young patients.
Several previous authors postulated that human papilloma virus, herpes simplex virus, and Epstein Barr virus
may play a pathogenetic role in head and neck carcinoma
in young patients, but no supportive evidence relative to
older patients was found.21,22 The association between
HNSCC and HPV has been studied intensively in the past
two decades and was found to be strongest for oropharyngeal SCC, specifically for cancers of the palatine and
lingual tonsils. In a landmark paper, HPV-16 seropositivity was most strongly associated with increased risk of
oropharyngeal cancer and was more weakly associated
with risk of developing oral cavity cancer.23 A recent
meta-analysis of 17 studies that aimed to define the association of HPV with the different head and neck subsites,
found that HPV is most strongly associated with tonsillar
cancer, is intermediate for oropharyngeal cancer in general, and is weakest for oral cancer.24 Overall, it seems
HPV is not associated with the recent surge in the incidence of biologically aggressive oral cavity cancer in
young populations.25
Genetic alterations and distinct molecular patterns have
also been studied in this context. It has been shown that
patients younger than 30 years exhibited a significantly
increased chromosome fragility compared to older
patients following mutagen exposure.22 In addition a
higher frequency of microsatellite instability has been

312 E. Soudry et al.

found in younger patients.22 Conversely, no significant

differences were found in the expression of p53, p21, Rb
and MDM2 proteins between patients younger than
35 years and older than 75 years.22 Thus the possible
influence of viruses and genetics in young patients
remains to be fully elucidated.
Synopsis of key findings

In conclusion, this study, although limited by sample size,

indicates that patients younger than 30 years with SCC of
the oral tongue more often present with more advanced
disease than older patients, and may have a distinct pattern of failure. These differences may be due to agerelated differences in the biologic behaviour of the
tumour or delayed cancer diagnosis owing to clinician
bias because of the patients younger age. Although oral
tongue SCC occurs rarely in younger adults, suspicious
lesions should not be disregarded, and histopathologically
proven tumours should be treated aggressively with intensive follow-up. Further studies are needed to elucidate the
biological factors underlying the development of tongue
cancer in young adults.
Conflict of interest

None to declare.
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