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Keywords:

  • squamous cell carcinoma;
  • epidemiology;
  • etiology;
  • tongue;
  • Scandinavia

Abstract

  1. Top of page
  2. Abstract
  3. MATERIAL AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

In several countries, increased incidence of squamous cell carcinoma (SCC) of the tongue in young adults has been suspected during the last decades. Some reports indicate a lower survival rate for young patients compared to older patients. In other reports, there has not been any considerable difference in survival when comparing young adults to older patients, whereas some authors have shown better survival for young adults. This disease is rare in young adults, and early reports were based on comparable small numbers and selected patients. Our aim was first to perform a population-based study to determine if an increased incidence in SCC of the tongue could be verified in a larger population comprising the Scandinavian countries Denmark, Finland, Sweden and Norway. A second aim was to determine survival rates for young adults compared to older patients. The material was based on the annual cancer incidence and survival reports from the Scandinavian cancer registries. The study period was 1960–1994. During that period, 5,024 SCCs of the tongue were reported. Of these, 276 (5.5%) were young adults (20–39 years). The incidence increased at all ages except for women 65–79 years old. The increase was most pronounced in young adults: 0.06–0.32 for men and 0.03–0.19 for women, counted by 100,000 person-years. Relative survival was significantly better for young adults compared to older patients. © 2002 Wiley-Liss, Inc.

During the past decades, an increased incidence of squamous cell carcinoma (SCC) of the tongue in young adults has been reported from several countries.1, 2, 3, 4 In some of these studies, the male-to-female ratio was lower in young than in older adults. Unlike the older patients, many of the young patients had never used tobacco or overconsumed alcohol. However, the time of exposure to these well-known carcinogens in most cases would not have been long enough for malignant transformation. This suggests that other external or internal factors play a role in the development of the disease in young adults. Hereditary effects may play a role in this type of early-onset cancer, though reports in the literature are contradictory.5, 6, 7

In several reports published since 1975, carcinoma of the tongue in young adults has been described as an aggressive disease. Some reports indicate a lower survival rate for young patients than for older patients suffering from the same disease.8, 9 Other clinical studies comparing young adults with groups of older patients report no significant differences in survival.10, 11, 12, 13, 14, 15 Some authors, in fact, show better survival for young patients.4, 16

In Sweden, tongue cancer constitutes 12% of all head-and-neck carcinomas. We have previously published results indicating a higher incidence of tongue cancer in young adults in Sweden during the past few decades.4 Due to the low incidence of the disease in the young population (only 4–5% of all patients with tongue carcinomas are under 40 years old at the time of diagnosis), earlier reports were based on very small numbers. Greater tumor material can be obtained from all of the Scandinavian countries combined (Denmark, Finland, Norway and Sweden), where cancer registration is compulsory and nearly all-inclusive. The registration process started in Denmark in 1942, and the other Nordic countries followed in the 1950s. An estimated 95% of all diagnosed tumors in these countries have been registered; therefore, a joint Scandinavian study provides an excellent opportunity for population-based studies regarding incidence and survival.

Our aim was first to determine whether an increased incidence in SCC of the mobile tongue in young adults over a 35-year period could be verified in a population of over 20 million Nordic people. A second aim was to compare the survival rates for young adults and older patients diagnosed with SCC of the tongue.

MATERIAL AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIAL AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

The material consists of data on primary SCCs of the mobile tongue reported to the Danish, Finnish, Norwegian and Swedish cancer registries during the study period, 1960–1994. Population and mortality data were obtained from national statistical yearbooks.

In the cancer registries, carcinoma of the tongue is coded according to the ICD-7 coding system with subsites. Base of the tongue is a subsite of the oropharynx category and therefore was not included in our study.

Prior to 1978, histology was not reported in Denmark. For incidence and estimates of numbers of cases of SCC of the tongue in Denmark for the period 1960–1977, see the following section. For survival analyses, only data from Denmark reported during 1978–1994 were used.

Cases were divided into 3 age groups: 20–39, 40–64 and 65–79 years at the time of diagnosis. The 20–39 group will be referred to as “young adults”. Cases diagnosed in patients younger than 20 years were excluded from the study since different mechanisms may play a role in carcinogenesis during childhood and adolescence. Most earlier reports used 40 years of age as the upper limit for young adults, and this limit was also used in the present study.

Statistical methods

As mentioned above, histology was not reported in Denmark prior to 1978; hence, the number of SCCs in Denmark for the period 1960–1977 was estimated as follows: the probability of SCC histology was modeled using logistic regression with country, sex, 3 age groups and 7 5-year periods as categorical factors. The calender year effect was highly significant, with a clear trend from 1960 to 1979: from 87% SCC histology in the beginning of the period to 94% at the end. The effects of country, sex and age group were small and far from significant when comparing models with and without these factors (p = 0.4, χ2 test with 6 degrees of freedom). Therefore, the proportion of SCC histology in Denmark in the different time periods before 1978 was estimated by the corresponding overall SCC percentages in the other Scandinavian countries, and the numbers of SCCs were obtained by multiplying these percentages with the total number of tongue cancers in the respective time periods.

To adjust for age differences between countries and time periods, cancer incidence was standardized for age using the standard European population17 as reference. The same relative weights were also used for the age-standardized incidence rates truncated to the ages 20–39, 40–64 and 65–79 years. Standard errors of the age-standardized incidence rates were calculated by assuming a Poisson-distributed number of cases.

Survival probability was estimated using life-table methods, and different groups were compared by means of log-rank tests. Many tongue cancer patients die from causes other than their cancer. Hence, relative survival was also estimated and compared for different groups.18 Nation-specific mortality data were used for calculating expected survival.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIAL AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

The total Scandinavian population is 23.2 million (as of 1995) and is made up of 8.8 million in Sweden, 5.1 million in Denmark, 5.0 million in Finland and 4.3 million in Norway. During the study period, 5,024 new cases of SCC of the mobile tongue were diagnosed in the studied age groups in these countries. The distribution by country, sex and 5-year periods can be seen in Table I.

Table I. Total Number of SCCs of the Tongue in Scandinavia Reported for the Period 1960–1994
 DenmarkFinlandNorwaySwedenTotal
  1. Numbers for Denmark for the years 1960–1977 have been estimated.

Males 20–79 years old     
 1960–196436564798237
 1965–1969516649135301
 1970–1974605180144335
 1975–1979826394173412
 1980–198410077114210501
 1985–198912799129213568
 1990–1994159109122229619
Females 20–79 years old     
 1960–1964386414104220
 1965–1969486431101244
 1970–1974345746108245
 1975–1979637650107296
 1980–1984667561109311
 1985–1989796577122343
 1990–19947311670133392

Altogether, 276 patients (5.5%) among the new cases were young adults at the time of diagnosis. Table II shows these cases distributed according to country, sex and 5-year period. During the study period, incidence increased in all age groups except for women aged 65–79 years, for whom the incidence remained constant. From the early 1960s to the 1990s, the incidence in young adults increased 5-fold, from 0.06 [95% confidence interval (CI) 0.02–0.11] to 0.32 (95% CI 0.25–0.41) per 100,000 person-years in men, and 6-fold, from 0.03 (95% CI 0.00–0.06) to 0.19 (95% CI 0.12–0.26) in women. In older patients, the incidence approximately doubled in both sexes: from 0.86 (95% CI 0.71–1.01) to 1.90 (95% CI 1.68–2.12) in men and from 0.58 (95% CI 0.46–0.70) to 1.01 (95% CI 0.85–1.17) in women aged 40–64 years and from 2.37 (95% CI 1.89–2.85) to 4.05 (95% CI 3.54–4.56) in men aged 65–79. As mentioned, in women aged 65–79 years, no incidence increase was seen, starting with 2.29 (95% CI 1.88–2.70) at the beginning of the study period and ending with 2.28 (95% CI 2.04–2.52) (Figs. 1, 2).

Table II. Total Number of SCCs of the Tongue in Young Adults in Scandinavia Reported for the Period 1960–1994
 DenmarkFinlandNorwaySwedenTotal
  1. Numbers for Denmark for the years 1960–1977 have been estimated.

Males 20–39 years old     
 1960–196414128
 1965–1969031711
 1970–197410258
 1975–1979784726
 1980–198411291234
 1985–19894871433
 1990–19941014102054
Females 20–39 years old     
 1960–196401124
 1965–196923106
 1970–1974143412
 1975–1979333312
 1980–1984273315
 1985–19892351222
 1990–199431261031
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Figure 1. SCC of the tongue. Incidence in Scandinavian men during 1960–1994 in the age groups 20–39, 40–64 and 65–79 years (logarithmic scale).

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Figure 2. SCC of the tongue. Incidence in Scandinavian women during 1960–1994 in the age groups 20–39, 40–64 and 65–79 years (logarithmic scale).

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The male-to-female incidence ratio in young adults was 1.98 at the beginning of the study period and 1.66 at the end. Corresponding figures were 1.48 and 1.89 for patients aged 40–64 and 1.03 and 1.77 for patients aged 65–79 years. Only in the 65–79 group was there a clear ratio increase, i.e., an increased preponderance of the disease in men.

Survival analyses show better crude as well as relative survival rates for young adults compared to older patients. The 5-year crude survival rate was 65% (95% CI 59–71%) for young adults, 45% (95% CI 43–48%) for the 40–64 group and 33% (95% CI 31–35%) for the 65–79 group.

Young adults showed significantly better relative survival than older patients (Fig. 3). The 5-year relative survival rate was 66% in young adults (95% CI 59–71%), 48% in the 40–64 group (95% CI 46–51%) and 43% in the 65–79 group (95% CI 40–45%).

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Figure 3. SCC of the tongue in Scandinavia in 1960–1994. Relative survival for the age groups 20–39, 40–64 and 65–79 years.

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DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIAL AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

In the present population study based on 5,024 incident cases of SCC of the tongue reported to the Scandinavian cancer registries between 1960 and 1994, 276 were young adults at the time of diagnosis. During the study period, a 6-fold increase in incidence was found in young adults. An increase was also observed in older patients; however, it was smaller than that in the young group.

Increased incidence in young adults has been reported from limited patient material. Shemen et al.3 described 38 male and 30 female young adults with tongue cancer from 1955 through 1982. Their study demonstrates an increased proportion of young adults, from 2.4% at the beginning of the study period to 16.2% at the end. Schantz et al.2 found an increased proportion of young adults with carcinoma of the tongue, from 0% in 1944 to 12% in 1984, based on 79 cases. However, these were hospital-based studies, which do not give adequate incidence rates in the total population. In contrast, Atula et al.10 reported that the total incidence of tongue cancer in Finland almost doubled from 1953 to 1992, with only a slight increase in the percentage of cases in younger patients, from 5.3% to 7.2%. The Finnish cases reported in our study were previously analyzed by Alho et al.19 These authors reported an increase in the incidence of tongue cancer at all ages, being most pronounced in the 0–69 group, but did not specifically analyze young adults (<40 years).

SCCs constitute 90–92% of all tongue carcinomas. The remaining 8–10% are composed of tumors such as adenocarcinomas, lymphomas and sarcomas and were excluded from our study since they are considered to differ from SCCs in terms of carcinogenesis and etiology. An advantage of the present study is the large number of patients, based on a population of 23.2 million people, which permitted us to study tongue cancer incidence trends in more detail.

For Denmark, histology was not reported before 1978. Analyzing the proportion of SCCs, we found a clearly increasing trend by time period but no effect of country, sex and age; hence, we estimated the proportion of SCCs in Denmark in the time periods before 1978 with the corresponding proportions in the other countries taken together. If the true proportion in Denmark deviated from that in the other countries in this period, this procedure would introduce a bias. However, since the proportion of SCCs is quite high (approx. 90%), the relative bias will probably be small. Moreover, since Denmark constitutes <25% of the study population, it is very unlikely that this bias would be significant. The alternative, not to include Denmark before 1978, would probably have caused worse problems since the population base for studying incidence trends would have changed in the middle of the study period.

The increased incidence in young adults cannot easily be explained. More accurate registration during the past 2 decades may explain part of the increase in registered cases. This presumption, however, was not supported by a quality-control study of the Cancer Registry of Norway.20 Earlier reports indicate less exposure in young adults to such risk factors as excessive alcohol intake and tobacco use. Furthermore, the exposure time in most cases of carcinoma of the tongue is too short in the young adult to have caused malignant transformation. However, it has been speculated that exposure of the epithelium to carcinogens at a young age may reduce the period of latency in carcinogenesis.21 Genetic susceptibility22, 23 may play a role in oral carcinogenesis together with exposure to external agents. In some patients, susceptibility to develop oral cancer may be explained by an impaired ability to repair damaged DNA. Young adults developing SCC of the head and neck may also have a changed ability to metabolize carcinogens or procarcinogens.24 A shift in exposure to external factors other than tobacco and alcohol, such as dental therapy methods, should also be investigated. Zhang et al.25 suggested that marijuana use may increase the risk of head-and-neck cancer. Smokeless tobacco has likewise been suggested as a risk factor, but the type of snuff used in Scandinavia has not shown any significant association with carcinogenesis.26, 27

Experimental models and analyses of oral tumors suggest that viral infections may be an etiologic factor.28, 29, 30 For instance, human papillomavirus (HPV) type 16 infection is suspected to have contributed to the development of a small proportion of oral SCCs in 3 counties in western Washington State.30 Mork et al.29 reported HPV-16 infection to be a risk factor and to be most pronounced in oropharyngeal cancer but associated to a lesser degree with tongue cancer. Further studies in this regard need to be performed to evaluate the viral role in carcinogenesis.

The present study indicates a significantly better survival rate for young adults than for older patients. This is in contrast to several earlier studies in which the prognosis was worse for young adults than for older patients.8, 9, 31 Several other early studies on the subject confirm our finding, however.4, 16 The discrepancy may be due to small numbers and selected patients in some reports. One explanation for the better survival in young patients in Scandinavia could be a higher proportion of T1 and T2 tumors since young patients can be expected to recognize their illness earlier. However, early lesions in this group may be neglected by patients, dentists and physicians, who do not expect to see tongue carcinomas in young individuals. Since the Scandinavian cancer registries do not contain TNM classification, it was not possible to adjust for stage. Mork and Glattre32 studied oral cancer patients from the Cancer Registry of Norway and found a tendency for improved survival among younger patients, even when patients with localized and regional disease were studied separately and when stratifying by age group. There may be an influence of the physician's choice of therapy since young patients can be expected to better stand treatment and recover more easily.

Nevertheless, it is of great importance for physicians to be aware of the fact that the increase in tongue cancer in young adults is a clinical reality and that any oral symptoms presented by a patient must therefore not be overlooked. As a delay in diagnosis affects the survival of the patient,33 early detection is of great importance.

In conclusion, we found that incidence of carcinoma of the tongue in young adults has increased 5-fold in men and 6-fold in women in Scandinavia during the study period. The incidence increase in other age groups for the same study period was much smaller. We also found that the relative survival was significantly better for young adults than for older patients.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIAL AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES