Squamous cell carcinoma (SCC) of the oral cavity is typically seen after the fifth decade of life, and it is the sixth most common cancer in the world (1). Less than 4% of these lesions occur in patients younger than 40 years old (2). However, oral cavity cancers in younger patients have recently increased, and especially in female patients who do not consume alcohol or tobacco (3). Oral cavity cancers in younger patients have been suggested to show different clinical characteristics and disease progression from that seen in older patients (4). Son and Kapp (2), Amsterdam and Strawitz (5), and Sasaki et al. (6) concluded that the young patients have worse clinical outcomes than do the older patients. However, Friedlander et al. (7) and Pitman et al. (8) noted no significant difference in outcome between different age groups, and McGregor et al. (9), Clark et al. (10), and Hafkamp et al. (11) reported better outcomes in the younger age groups.

Thus, the previous studies have reported conflicting results about the clinical characteristics of oral cavity cancer in the young age groups, as well as having used different cutoff levels of age. In addition, there is a lack of reports that have compared between different age groups.

The purpose of this study was to analyze the recurrence and survival rates of SCC of the tongue in young patients who are under 45 years of age, and to compare them with older patients who have SCC of the tongue and who are over the age of 45 years.

We retrospectively reviewed 105 patients who were treated for SCC of the tongue at our hospital between December 1994 and September 2008. Eighty-five patients were included who had not been treated before hospitalization for the same diagnosis, and they received their initial surgical treatment with a curative intent and a minimum follow up of 12 months. Twenty patients did not have sufficient data and they were excluded. Primary resection and neck dissection with an en bloc pattern was the surgical treatment for most patients in both groups. Selective neck dissection was done with a prophylactic intent for the clinically negative necks, and modified radical neck dissection was done for the clinically positive necks. In the limited cases of early cancer (<1 cm), primary resection was done without neck dissection. Adjuvant treatment was considered when the cancer free margin was insufficient (<5 mm) or when extracapsular invasion was found, or if multiple nodal metastases were found. Most patients were followed-up every 6 months for the first 2 years and then they were followed up every 12 months. The follow-up modalities were computed tomography (CT), magnetic resonance imaging (MRI) and a liver/bone scan or positron emission tomography (PET)/CT.

The study group was divided into two age groups with a cutoff level of 45 years. The following data was recorded from the patient files: age, gender, tobacco and alcohol consumption, staging, pathology, the treatment modalities, the length of the hospital stay and the clinical outcome. To evaluate the clinical outcome, we analyzed the recurrence rate, the site of recurrence and the overall and disease specific survival rates. The patients were staged according to the 2002 American Joint Committee on Cancer (AJCC) staging system. The institutional review board approved the retrospective review of the medical records.

SCC of the oral cavity is a rare disease in young people; fewer than 4% of these lesions occur in patients younger than 40 years of age (2). About 30% of the patients with SCC of the oral cavity have been reported to be younger than 45 years (12, 13).

Oral cavity cancers in young patients have recently increased, and especially in female patients who do not consume alcohol or tobacco. This disease has been suggested to show different clinical characteristics and disease progression from that in older patients (4). Atula et al. (14) in Finland found that the percentage of SCC of the tongue occurring in young adults had increased from 3% per year for the decade between 1953 to 1962 to 7% annually for the decade between 1983 to 1992. Lingen et al. (15) revealed that an increased p53 expression without a mutation in exon 5-9 was found in the SCC of the oral cavity in young, nonsmoking patients. Sorenson et al. (16) showed that the p53 mutation was less common in the tongue cancer of young patients with no history of alcohol or tobacco use.

We divided the patients who were diagnosed with SCC of the tongue into two age groups: over and under 45 years of age. We decided on this cutoff age based on the previous studies (2, 17). About 27% of the patients were under 45 years in our study group, and this was consistent with the previous studies (12-14).

Our findings were consistent with previous studies reporting that alcohol and tobacco use were less common in younger patients. No significant difference in smoking could be assessed due to the lack of data for some patients.

Friedlander et al. (7) and Pitman et al. (8) noted no significant difference in the outcome between different age groups. However, McGregor et al. (9), Clark et al. (10), and Hafkamp et al. (11) noted that the outcome of the younger group was better. Son and Kapp (2), Amsterdam and Strawitz (5), and Sasaki et al. (6) concluded that younger patients had worse clinical outcomes than did the older patients. Vargas et al. (18), in their study of 17 young females with invasive SCC of the tongue, they found that young women with SCC of the anterior tongue had significantly higher rates of recurrent disease and that the interval to recurrence was significantly shorter than that of older patients. The conflicting and inconsistent results of the previous reports seem to be due to the small numbers of patients in the young groups.

Our current report is partially consistent with the studies that found a worse prognosis in younger patients with tongue cancer. In the early-stage group, the recurrence rate was low and the survival rate was high for all ages. However, in the advanced-stage group, the recurrence rate was higher for the young patients, and especially for regional recurrence. In total, eight (88%) recurrent cases were seen in the young patients. There were six (66%) regional recurrences in the young patients, two of which were exclusively in the contralateral neck (level I, II). In the ipsilateral neck, there were four regional recurrences, and all of them were in level I. Regarding the possible cause of recurrence, two cases were treated by ipsilateral selective neck dissection with a prophylactic intent because of the clinical N0 stage. Subsequently, they were pathologic N2 stage and they recurred in the contralateral neck. Ipsilateral selective neck dissection is thought to be insufficient to eradicate neck disease. Three of the recurrent cases had multiple positive nodes pathologically (more than 13), and extracapsular invasion was found and they all recurred in level I. In one case, we found no obvious reason for recurrence. In two locally recurrent cases, the lack of a cancer-free margin was thought to be the reason for recurrence.

As noted previously, failure of regional control seemed to be the main cause of a poor prognosis in the young group. In the recurrent cases, the nodal disease was more aggressive than we had staged preoperatively. Thus, we think that more aggressive neck treatment may have prevented regional recurrence. However, a limitation of this study is its small sample size, and a larger multicenter study is needed.

According to our results, when the cancer is at an early stage, the outcome is similar at all ages, but as the cancer progresses, it transformed to a more aggressive form in the younger patients. This may have been due to different carcinogenesis at the gene level, so molecular studies would be useful.

In conclusion, tongue cancer at a young age has significantly different clinical outcome according to the tumor stage. Because advanced-stage tongue cancer leads to morbidity with a poor overall outcome and especially in young patients, it is important to detect it at an early stage. Regional recurrence seems to be main cause of the poor prognosis, and so we cautiously recommend that more complete neck treatment is needed.