Abstract
1.1. Objectives:
Although oral cancers traditionally occur in people between the age of 50 and 70, there are increasing incidences of this disease in younger and very old people. Objectives: to compare the demographics, habits, clinicopathological features, treatment and outcome of oral cancer in three age groups of patients: Young (≤ 45), Traditional (46 to 75), and Old (> 75).
1.2. Subjects:
Primary oral cancers (393 patients) in a longitudinal study were used.
1.3. Results:
Significant differences were noted in ethnicity (fewer Caucasian patients in Young), tobacco habit (more non-smokers in Young), location of cancer (more at tongue for Young and more at low-risk sites for Old) and treatment (more surgery for Young). Compared to Young (univariate analysis), Traditional and Old showed a 3- and 4.5-fold increase in local recurrences respectively; 1.9- and 2.7-fold increase in regional metastasis; 3.1- and 5.4-fold increase in death due to disease; and a 3.4- and 6.6-fold decrease in overall survival. Compared to Young (multivariate analysis), Traditional and Old showed a 2.4- and 3.3-fold increase in local recurrence; 2.7- and 5.4-fold increase in disease-specific survival; and 2.8- and 6.5-fold decrease in overall survival.
1.4. Conclusion:
Oral cancer in different age groups showed differing ethnicity, habit, location, treatment and outcome.
2. Introduction
Oral Squamous Cell Carcinoma (OSCC) is one of the most common human cancers with poor prognosis. Until recently, OSCCs have been diagnosed mostly in patients in their sixth or seventh decade of life, with the disease often associated with a history of heavy tobacco consumption [1]. However, the incidence of OSCC in younger individuals (≤ 45 years old, hereby called Young) is rising [2–8], including in British Columbia [9]. At the same time, the extension of life expectancy has led to an aging population (> 75 years old, hereby called Old) both globally and in Canada, with an expected increase of Old oral cancer patients [4,10–12].
The age shift has prompted studies of OSCC in Young and Old patients because the understanding of clinicopathological features, treatment response and outcome of these patients would provide knowledge for better cancer control and management. However, results from studies comparing OSCCs among different age groups to date have been inconsistent. For example, prognosis of clinical outcomes among various age groups remains controversial. Kuriakose et al [13], and others [14–16] found that the disease was more aggressive in Young OSCC patients, whereas other studies reported better prognosis in Young, and still others could not find any significant differences [17–20]. Such inconsistency could be explained by a number of factors, such as the small number of cases in most of these studies, differences in genetic makeup of various ethnic groups and dissimilarities in dietary habits of diverse cultures. This study was aimed to obtain information (habits, clinicopathological features, treatment and outcome) of Young and Old OSCC patients from the greater Vancouver region in a longitudinal study setting.
3. Materials and Methods
This study involved patients who were prospectively enrolled in a longitudinal study (the Oral Cancer Predictive and Longitudinal, OCPL) in greater Vancouver, British Columbia (BC), Canada between 1997and 2009. Patients were identified primarily through a centralized oral pathology service, the BC Oral Biopsy Service, which receives biopsies from dentists and ENT surgeons across the province. Patients with oral cancer were referred to five Oral Dysplasia Clinics in Greater Vancouver where they were accrued to the study using written informed consent and a study protocol approved by research ethics board at the UBC/BCCA (University of BC/BC Cancer Agency; H98–61224 and H08–00839).
A total of 423 OSCC patients were recruited to the OCPL study. Of these. 393 patients met the inclusion criteria for this study:
A histological diagnosis of OSCC
No prior history of OSCC
The cancer was treated with a curative intent, which was defined as complete removal of the cancer or radiotherapy aimed at cure and
at least a 6-month follow-up time to ensure that each case had received and completed treatment.
Since the recruitment occurred at Oral Dysplasia Clinics from a dental and ENT network, some OSCC, particularly those late stage ones (stage III and IV) were diagnosed by family doctors (biopsies did not go to the BC Oral Biopsy Service), hence were missing from our recruitment. As a result, the OSCC patients in our study had less representation of late-stage OSCC patients.
The following data were collected at study entry and during patient follow-up: habit (tobacco usage), demographics (age at cancer diagnosis, gender and ethnicity), clinicopathological (anatomical site, TNM stage and histopathological grade of the cancer), treatment, and outcome information (local recurrence to carcinoma in situ or invasive SCC, lymph node metastasis, distant metastasis and death). These data were entered into the OSCC database. When the information was not complete for this study, chart review was done.
Among these 393 cases, the average age was 60 years with a standard deviation of 13 years. For the ‘Young’ group, we used 45 years as the age cut off, which was derived both from previous studies (many used ≤ 45 as the age cut off) [21–27] and from calculation of one standard deviation younger than the average age [average age (60) - 1SD (13) = 47]. For the Old group, we used older than 75 as the cut off, which again came from previous studies [12,28,29] and from calculation [average age (60) + 1SD (13) = 73]. These cutoff values resulted in a separation of the study population (n = 393) into 3 groups, 55 (14%) patients were in the Young group (≤ 45); 295 (75%) were between the ages of 46 and 75, or ‘traditional’ age group (hereby called Traditional group); and 43 (11%) were in the Old group (> 75).
4. Statistical Analysis
Differences between two age groups (Young vs Traditional or Young vs Old, or Traditional vs Old) were examined using either Fisher’s exact test for categorical variables (gender, ethnicity, smoking habit, tumor size and histological grade) or t-test for continuous variables (age and follow-up time). Time to endpoint was calculated from date of the index biopsy to endpoint date or to last follow-up date before February 2014 if no event occurred. Time-to-outcome curves were estimated using Kaplan–Meier analysis. Hazard ratios (HRs) and the corresponding 95% confidence intervals (95% CI) were determined using Cox proportional hazard regression analysis. Univariate logistic analysis and multiple proportional hazards regression analysis were used for estimating the HR of individual variable and combined effect. All tests were two sided with P ≤ 0.05 considered to be statistically significant.
5. Results
Table 1 shows demographics, tobacco habit, clinical features (site and TNM stage), histology, treatment and follow up time for all patients in the current study by age groups. The mean follow up time for the study was 5.1 ± 3.4 years and the median 4.6 years. There were no differences in gender, TNM stage and histological differentiation of the OSCCs among the three age groups. However, differences were noted in ethnicity (less Caucasian in Young), habits (more non-smokers in Young), location (more at tongue for Young and low-risk sites for Old) and treatment (more surgery for Young).
Table 1:
Comparison of the Three Age Groups.
| Characteristics | All | Young (Y) | Traditional | Old (O) | P value | P value | P value |
|---|---|---|---|---|---|---|---|
| (T) | Y vs. T | Y vs. O | O vs. T | ||||
| Case Number | 393 | 55 | 293 | 45 | |||
| Age (years) | |||||||
| Mean age ± SD | 60.4 ± 13.4 | 37.3 ± 7.7 | 61.6 ± 7.6 | 81.1 ± 4.0 | |||
| Gender | |||||||
| Male | 246 (63) | 33 (60) | 189 (65) | 24 (53) | 0.54 | 0.55 | 0.18 |
| Female | 147 (37) | 22 (40) | 104 (35) | 21 (47) | |||
| Ethnicity | |||||||
| Caucasian | 326 (83) | 40 (73) | 247 (84) | 39 (87) | 0.05 | 0.14 | 0.83 |
| Non-Caucasiana | 67 (17) | 15 (27) | 46 (16) | 6 (13) | |||
| Smoking | |||||||
| Never smokerb | 121 (31) | 34 (62) | 72 (25) | 15 (33) | <0.0001 | <0.0001 | 0.21 |
| Ever smokerc | 272 (69) | 21 (38) | 221 (75) | 30 (67) | |||
| Former-smokerd | 132 (49) | 9 (43) | 98 (44) | 25 (83) | 1 | 0.006 | <0.0001 |
| Current-smokere | 140 (51) | 12 (57) | 123 (56) | 5 (17) | |||
| Site | |||||||
| Tonguef | 204 (52) | 47 (85) | 136 (46) | 21 (47) | <0.0001 | <0.0001 | 0.04 |
| FOM (floor of mouthf | 76 (19) | 4 (7) | 68 (23) | 4 (9) | |||
| Soft Palateg | 15 (4) | 0 (0) | 14 (5) | 1 (2) | |||
| Low risk sitesh | 98 (25) | 4 (7) | 75 (26) | 19 (42) | |||
| TNM Stage | |||||||
| Early (stages I and II) | 287 (73) | 43 (78) | 211 (72) | 33 (73) | 0.41 | 0.64 | 1 |
| Late (stages III and IV) | 106 (27) | 12 (22) | 82 (28) | 12 (27) | |||
| Histology | |||||||
| Well-moderate | 370 (94) | 53 (96) | 274 (94) | 43 (96) | 0.55 | 0.59 | 1 |
| Poor | 23 (6) | 2 (4) | 19 (6) | 2 (4) | |||
| Treatment | |||||||
| Surgery | 268 (68) | 41 (74) | 197 (67) | 30 (67) | 0.009 | <0.0001 | 0.13 |
| Surgery & radiation | 62 (16) | 13 (24) | 50 (17) | 3 (7) | |||
| Radiation | 63 (16) | 1 (2) | 46 (16) | 12 (27) | |||
| Surgery with or without radiation | 330 (84) | 54 (98) | 247 (84) | 33 (73) | 0.004 | 0.0004 | 0.09 |
| Radiation | 63 (16) | 1 (2) | 46 (16) | 12 (27) | |||
| Follow up time (years) | |||||||
| Mean ± SD | 5.1 ± 3.4 | 6.9 ± 3.3 | 5.0 ± 3.3 | 3.3 ± 2.5 | <0.0001 | <0.0001 | 0.002 |
| Median | 4.6 | 7.4 | 4.5 | 2.6 |
Significant values, P < 0.05, are bolded.
Non-Caucasian; Asian, First Nation, Hispanic and more than one race.
Never smoker was defined as consumption of less than 100 cigarettes in life time.
Ever Smoker was defined as consumption of more than 100 cigarettes in life time.
Former smoker: Smokers who had stopped smoking after enrolling into the study.
Current smoker: Smokers who continued smoking after enrolling into the study.
Tongue and Floor of Mouth (FOM): are regarded high risk sites where oral premalignant lesions are at high risk of malignant transformation.
Soft palate: is regarded an intermediate risk site where oral premalignant lesions are at an intermediate risk of malignant transformation.
Low-risk sites: Gingiva, vestibule, cheek, lip and hard palate.
Univariate Cox analyses were performed using different outcomes, with local recurrence as outcome shown in Table 2, lymph node metastasis as outcome in Table 3, distant metastasis as outcome in Table 4, disease-specific survival as outcome in Table 5 and overall survival as outcome in Table 6. Increasing ages, location at high-risk sites, and radiation treatment were associated with increased risk of local recurrence; increasing age, Caucasian ethnicity, site (high- or intermediate-risk) and late TNM stages were associated with significantly higher proportion of lymph node metastasis; locations at floor of mouth/soft palate and late TNM stages were associated with significantly higher proportion of distant metastasis; increasing age, location at floor of mouth, late TNM stages and radiation treatment were associated with significantly higher proportion of death due to disease; and increasing age, Caucasian ethnicity, tobacco habit, locations at floor of mouth/soft palate, late TNM stages and radiation treatment were associated with poorer overall survival.
Table 2:
Univariate and Multivariate Analyses with Local Recurrence as Outcome.
| Characteristics | All | With outcome | Without outcome | Univariate analysis | Multivariate analysis | ||
|---|---|---|---|---|---|---|---|
| (% row) | (% row) | HR (95% CI)a | P value | HR (95% CI) | P value | ||
| Case Number | 393 | 104 (26) | 289 (74) | ||||
| Age | |||||||
| Young | 55 | 7 (13) | 48 (87) | 1 | 1 | ||
| Traditional | 293 | 83 (28) | 210 (72) | 3.0 (1.4 – 6.6) | 0.01 | 2.4 (1.0 – 5.3) | 0.04 |
| Old | 45 | 14 (31) | 31 (69) | 4.5 (1.8 – 11.2) | 0.001 | 3.3 (1.3 – 8.5) | 0.02 |
| Gender | |||||||
| Female | 147 | 41 (28) | 106 (72) | 1 | 0.77 | 1 | 0.58 |
| Male | 246 | 63 (26) | 183 (74) | 0.9 (0.6 – 1.4) | 0.9 (0.6 – 1.4) | ||
| Ethnicity | |||||||
| Caucasian | 326 | 81 (25) | 245 (75) | 1 | 0.49 | 1 | 0.15 |
| Non-Caucasianb | 67 | 23 (34) | 44 (66) | 1.2 (0.7 – 1.9) | 1.5 (0.9 – 2.4) | ||
| Smoking | |||||||
| Never-smokerc | 121 | 27 (22) | 94 (78) | 1 | 0.12 | 1 | NA |
| Ever-smokerd | 272 | 77 (28) | 195 (72) | 1.4 (0.9 – 2.2) | NA | ||
| Former-smokere | 132 | 40 (30) | 92 (70) | 1.5 (0.9 – 2.5) | 0.09 | 1.4 (0.8 – 2.4) | 0.25 |
| Current-smokerf | 140 | 37 (26) | 103 (74) | 1.3 (0.8 – 2.1) | 0.3 | 1.1 (0.6 – 2.0) | 0.74 |
| Site | |||||||
| Tongueg | 204 | 44 (22) | 160 (78) | 1 | 1 | ||
| FOMg | 76 | 21 (28) | 55 (72) | 1.6 (1.0 – 2.8) | 0.06 | 1.4 (0.8 – 2.5) | 0.25 |
| Soft palateh | 15 | 4 (27) | 11 (73) | 1.8 (0.6 – 4.9) | 0.28 | 1.0 (0.3 – 3.2) | 0.94 |
| Low-risk sitesi | 98 | 35 (36) | 63 (64) | 1.9 (1.2 – 3.0) | 0.004 | 1.3 (0.8 – 2.1) | 0.34 |
| TNM Stage | |||||||
| Early | 287 | 73 (25) | 214 (75) | 1 | 0.09 | 1 | 0.28 |
| Late | 106 | 31 (29) | 75 (71) | 1.4 (0.9 – 2.3) | 1.3 (0.8 – 2.0) | ||
| Histology | |||||||
| Well-moderate | 371 | 100 (27) | 271 (73) | 1 | 0.32 | NA | NA |
| Poor | 22 | 4 (18) | 18 (82) | 0.6 (0.2 – 1.6) | NA | ||
| Treatment | |||||||
| Surgery with or without radiation | 330 | 76 (23) | 254 (77) | 1 | <0.0001 | 1 | 0.02 |
| Radiation | 63 | 28 (44) | 35 (56) | 2.4 (1.5 – 3.7) | 1.8 (1.1 – 3.1) | ||
Significant values, P < 0.05, are bolded.
HR: indicates a hazard ratio; CI: confidence interval.
Non-Caucasian; Asian, First Nation, Hispanic and more than one race.
Never smoker was defined as consumption of less than 100 cigarettes in life time.
Ever Smoker was defined as consumption of more than 100 cigarettes in life time.
Former smoker: Smokers who had stopped smoking after enrolling into the study.
Current smoker: Smokers who continued smoking after enrolling into the study.
Tongue and floor of mouth (FOM): are regarded high risk sites where oral premalignant lesions are at high risk of malignant transformation.
Soft palate: is regarded intermediate risk site where oral premalignant lesions are at an intermediate risk of malignant transformation.
Low-risk sites: Gingiva, vestibule, cheek, hard palate and labial mucosa.
Table 3:
Univariate and Multivariate Analyses with Regional Lymph Node Failure as Outcome.
| Characteristics | All | With outcome | Without outcome (% row) | Univariate analysis | Multivariate analysis | ||
|---|---|---|---|---|---|---|---|
| (% row) | HR | P value | HR (95% CI) | P value | |||
| (95% CI)a | |||||||
| Case Number | 393 | 82 (21) | 311 (79) | ||||
| Age | |||||||
| Young | 55 | 7 (13) | 48 (87) | 1 | 1 | ||
| Traditional | 293 | 63 (22) | 230 (78) | 1.9 (0.9 – 4.2) | 0.1 | 2.1 (0.9 – 4.8) | 0.07 |
| Old | 45 | 12 (27) | 33 (73) | 2.7 (1.1 – 6.9) | 0.04 | 4.2 (1.6 – 11.4) | 0.004 |
| Gender | |||||||
| Female | 147 | 30 (20) | 117 (80) | 1 | 0.81 | 1 | 0.92 |
| Male | 246 | 52 (21) | 194 (79) | 1.1 (0.7 – 1.7) | 1.0 (0.6 – 1.6) | ||
| Ethnicity | |||||||
| Caucasian | 326 | 74 (23) | 252 (77) | 1 | 0.04 | 1 | 0.08 |
| Non-Caucasianb | 67 | 8 (12) | 59 (88) | 0.5 (0.2 – 1.0) | 0.5 (0.2 – 1.1) | ||
| Smoking | |||||||
| Never-smokerc | 121 | 23 (19) | 98 (81) | 1 | 0.52 | 1 | NA |
| Ever-smokerd | 272 | 59 (22) | 213 (78) | 1.2 (0.7 – 1.9) | NA | ||
| Former-smokere | 132 | 26 (20) | 106 (80) | 1.0 (0.6 – 1.8) | 0.88 | 0.8 (0.4 – 1.4) | 0.43 |
| Current-smokerf | 140 | 33 (24) | 107 (76) | 1.3 (0.8 – 2.2) | 0.34 | 1.1 (0.6 – 2.0) | 0.82 |
| Site | |||||||
| Tongueg | 204 | 49 (24) | 155 (76) | 1 | 1 | ||
| FOMg | 76 | 19 (25) | 57 (75) | 1.1 (0.7 – 1.9) | 0.66 | 1.0 (0.5 – 1.7) | 0.87 |
| Soft palateh | 15 | 4 (27) | 11 (73) | 1.2 (0.4 – 3.4) | 0.71 | 1.6 (0.5 – 5.1) | 0.44 |
| Low-risk sitesi | 98 | 10 (10) | 88 (90) | 0.4 (0.2 – 0.8) | 0.01 | 0.4 (0.2 – 0.7) | 0.01 |
| TNM Stage | |||||||
| Early | 287 | 54 (19) | 233 (81) | 1 | 0.03 | 1 | 0.01 |
| Late | 106 | 28 (26) | 78 (74) | 1.7 (1.1 – 2.7) | 1.8 (1.1 – 2.9) | ||
| Histological | |||||||
| Well-moderate | 371 | 79 (21) | 292 (79) | 1 | 0.46 | NA | NA |
| Poor | 22 | 3 (14) | 19 (86) | 0.6 (0.2 – 2.1) | |||
| Treatment | |||||||
| Surgery with or without radiation | 330 | 73 (22) | 257 (78) | 1 | 0.26 | 1 | 0.16 |
| Radiation | 66 | 9 (14) | 54 (86) | 0.7 (0.3 – 1.3) | 0.6 (0.2 – 1.3) | ||
Significant values, P < 0.05, are bolded.
HR: indicates a hazard ratio; CI: confidence interval.
Non-Caucasian; Asian, First Nation, Hispanic and more than one race.
Never smoker was defined as consumption of less than 100 cigarettes in life time.
Ever Smoker was defined as consumption of more than 100 cigarettes in life time.
Former smoker: Smokers who had stopped smoking after enrolling into the study.
Current smoker: Smokers who continued smoking after enrolling into the study.
Tongue and Floor of Mouth (FOM): are regarded high risk sites where oral premalignant lesions are at high risk of malignant transformation.
Soft palate: is regarded intermediate risk site where oral premalignant lesions are at an intermediate risk of malignant transformation.
Low-risk sites: Gingiva, vestibule, cheek, hard palate and labial mucosa.
Table 4:
Univariate and Multivariate Analyses with Distant Metastasis as Outcome
| Characteristics | All | With outcome (% row) | Without outcome (% row) | Univariate analysis | Multivariate analysis | ||
|---|---|---|---|---|---|---|---|
| HR (95% CI)a | P value | HR | P value | ||||
| (95% CI) | |||||||
| Case Number | 393 | 29 (7) | 364 (93) | ||||
| Age | |||||||
| Young | 55 | 2 (4) | 53 (96) | 1 | 1 | ||
| Traditional | 293 | 25 (9) | 268 (91) | 2.9 (0.7 – 12.3) | 0.15 | 2.1 (0.5 – 9.7) | 0.32 |
| Old | 45 | 2 (4) | 43 (96) | 2.0 (0.3 – 14.3) | 0.49 | 1.9 (0.2 – 14.7) | 0.56 |
| Gender | |||||||
| Female | 147 | 12 (8) | 135 (92) | 1 | 0.71 | 1 | 0.41 |
| Male | 246 | 17 (7) | 229 (93) | 0.9 (0.4 – 1.8) | 0.7 (0.3 – 1.6) | ||
| Ethnicity | |||||||
| Caucasian | 326 | 26 (8) | 300 (92) | 1 | 0.23 | 1 | 0.41 |
| Non-Caucasianb | 67 | 3 (4) | 64 (96) | 0.5 (0.1 – 1.6) | 0.6 (0.2 – 2.1) | ||
| Smoking | |||||||
| Never-smokerc | 121 | 7 (6) | 114 (94) | 1 | 0.36 | 1 | NA |
| Ever-smokerd | 272 | 22 (8) | 250 (92) | 1.5 (0.6 – 3.5) | NA | ||
| Former-smokere | 132 | 10 (8) | 122 (92) | 1.4 (0.5 – 3.6) | 0.52 | 1.0 (0.3 – 2.8) | 0.94 |
| Current-smokerf | 140 | 12 (9) | 128 (91) | 1.6 (0.6 – 4.1) | 0.32 | 0.9 (0.3 – 2.7) | 0.87 |
| Site | |||||||
| Tongueg | 204 | 11 (5) | 193 (95) | 1 | 1 | ||
| FOMg | 76 | 9 (12) | 67 (88) | 2.7 (1.1 – 6.5) | 0.03 | 2.3 (0.9 – 6.2) | 0.09 |
| Soft palateh | 15 | 3 (20) | 12 (80) | 4.6 (1.3 – 16.4) | 0.02 | 4.9 (1.0 – 23.4) | 0.04 |
| Low-risk sitesi | 98 | 6 (6) | 92 (94) | 1.2 (0.4 – 3.2) | 0.73 | 1.1 (0.4 – 3.1) | 0.92 |
| TNM Stage | |||||||
| Early | 287 | 17 (6) | 270 (94) | 1 | 0.01 | 1 | 0.02 |
| Late | 106 | 12 (11) | 94 (89) | 2.6 (1.2 – 5.5 ) | 2.6 (1.2 – 5.7) | ||
| Histological | |||||||
| Well-moderate | 371 | 27 (7) | 344 (93) | 1 | 0.67 | NA | NA |
| Poor | 22 | 2 (9) | 20 (91) | 1.4 (0.3 – 5.8) | |||
| Treatment | |||||||
| Surgery with or without radiation | 330 | 23 (7) | 307 (93) | 1 | 0.31 | 1 | 0.78 |
| Radiation | 63 | 6 (10) | 57 (90) | 1.6 (0.7 – 3.9) | 0.9 (0.3 – 2.6) | ||
Significant values, P < 0.05, are bolded.
HR: indicates a hazard ratio; CI: confidence interval.
Non-Caucasian; Asian, First Nation, Hispanic and more than one race.
Never smoker was defined as consumption of less than 100 cigarettes in life time.
Ever Smoker was defined as consumption of more than 100 cigarettes in life time.
Former smoker: Smokers who had stopped smoking after enrolling into the study.
Current smoker: smokers who continued smoking after enrolling into the study.
Tongue and Floor of Mouth (FOM): are regarded high risk sites where oral premalignant lesions are at high risk of malignant transformation.
Soft palate: is regarded intermediate risk site where oral premalignant lesions are at an intermediate risk of malignant transformation.
Low-risk sites: Gingiva, vestibule, cheek, hard palate and labial mucosa.
Table 5:
Univariate and Multivariate Analyses with Disease-Specific Survival (Death Due to Disease) as Outcome.
| Characteristics | All | With outcome | Without outcome | Univariate analysis | Multivariate analysis | ||
|---|---|---|---|---|---|---|---|
| (% row) | (% row) | HR | P value | HR | P value | ||
| (95% CI)a | (95% CI) | ||||||
| Case Number | 393 | 86 (22) | 307 (78) | ||||
| Age | |||||||
| Young | 55 | 5 (9) | 50 (91) | 1 | 1 | ||
| Traditional | 293 | 67 (23) | 226 (77) | 3.1 (1.3 – 7.7) | 0.01 | 2.7 (1.1 – 7.0) | 0.04 |
| Old | 45 | 14 (31) | 31 (69) | 5.4 (1.9 – 15.1) | 0.001 | 5.4 (1.8 – 16.1) | 0.003 |
| Gender | |||||||
| Female | 147 | 29 (20) | 118 (80) | 1 | 0.43 | 1 | 0.67 |
| Male | 246 | 57 (23) | 189 (77) | 1.2 (0.8 – 1.9) | 1.1 (0.7 – 1.8) | ||
| Ethnicity | |||||||
| Caucasian | 326 | 79 (24) | 247 (76) | 1 | 0.01 | 1 | 0.08 |
| Non-Caucasianb | 67 | 7 (10) | 60 (90) | 0.4 (0.2 – 0.8) | 0.5 (0.2 – 1.1) | ||
| Smoking | |||||||
| Never-smokerc | 121 | 22 (18) | 99 (82) | 1 | 0.25 | 1 | NA |
| Ever-smokerd | 272 | 64 (24) | 208 (76) | 1.3 (0.8 – 2.2) | NA | ||
| Former-smokere | 132 | 33 (25) | 99 (75) | 1.4 (0.8 – 2.4) | 0.22 | 0.8 (0.5 – 1.5) | 0.53 |
| Current-smokerf | 140 | 31 (22) | 109 (78) | 1.3 (0.7 – 2.2) | 0.4 | 0.7 (0.4 – 1.3) | 0.31 |
| Site | |||||||
| Tongueg | 204 | 38 (19) | 166 (81) | 1 | 1 | ||
| FOMg | 76 | 22 (29) | 54 (71) | 1.8 (1.1 – 3.1) | 0.02 | 1.4 (0.8 – 2.5) | 0.25 |
| Soft palateh | 15 | 6 (40) | 9 (60) | 2.6 (1.1 – 6.1) | 0.03 | 2.8 (1.0 – 7.5) | 0.05 |
| Low-risk sitesi | 98 | 20 (20) | 78 (80) | 1.1 (0.7 – 1.9) | 0.65 | 0.8 (0.4 – 1.5) | 0.47 |
| TNM Stage | |||||||
| Early | 287 | 41 (14) | 246 (86) | 1 | < 0.0001 | 1 | < 0.0001 |
| Late | 106 | 45 (42) | 61 (58) | 3.9 (2.5 – 5.9) | 3.6 (2.3 – 5.6) | ||
| Histology | |||||||
| Well-Moderate | 371 | 80 (22) | 291 (78) | 1 | 0.62 | NA | NA |
| Poorly | 22 | 6 (27) | 16 (73) | 1.2 (0.5 – 2.8) | |||
| Treatment | |||||||
| Surgery with or without radiation | 330 | 65 (20) | 265 (80) | 1 | 0.01 | 1 | 0.94 |
| Radiation | 63 | 21 (33) | 42 (67) | 1.9 (1.2 – 3.1) | 1.0 (0.6 – 1.9) | ||
Significant values, P < 0.05, are bolded.
HR: indicates a hazard ratio; CI: confidence interval.
Non-Caucasian; Asian, First Nation, Hispanic and more than one race.
Never smoker was defined as consumption of less than 100 cigarettes in life time.
Ever Smoker was defined as consumption of more than 100 cigarettes in life time.
Former smoker: Smokers who had stopped smoking after enrolling into the study.
Current smoker: Smokers who continued smoking after enrolling into the study.
Tongue and Floor of Mouth (FOM): are regarded high risk sites where oral premalignant lesions are at high risk of malignant transformation.
Soft palate: is regarded intermediate risk site where oral premalignant lesions are at an intermediate risk of malignant transformation.
Low-risk sites: Gingiva, vestibule, cheek, hard palate and labial mucosa.
Table 6:
Univariate and Multivariate Analyses with Overall Survival as Outcome.
| Characteristics | All | With outcome (% row) | Without outcome (% row) | Univariate analysis | Multivariate analysis | ||
|---|---|---|---|---|---|---|---|
| HR | P value | HR | P value | ||||
| (95% CI)a | (95% CI) | ||||||
| Case Number | 393 | 143 (36) | 250 (64) | ||||
| Age | |||||||
| Young | 55 | 8 (15) | 47 (85) | 1 | 1 | ||
| Traditional | 293 | 111 (38) | 182 (62) | 3.4 (1.7 – 7.1) | 0.001 | 2.8 (1.3 – 5.9) | 0.01 |
| Old | 45 | 24 (53) | 21 (47) | 6.6 (3.0 – 14.8) | < 0.0001 | 6.5 (2.7 – 15.3) | < 0.0001 |
| Gender | |||||||
| Female | 246 | 45 (31) | 102 (69) | 1 | 0.11 | 1 | 0.45 |
| Male | 147 | 98 (40) | 148 (60) | 1.3 (0.9 – 1.9) | 1.2 (0.8 – 1.7) | ||
| Ethnicity | |||||||
| Caucasian | 326 | 130 (40) | 196 (60) | 1 | 0.001 | 1 | 0.06 |
| Non-Caucasianb | 67 | 13 (19) | 54 (81) | 0.4 (0.2 – 0.7) | 0.6 (0.3 – 1.0) | ||
| Smoking | |||||||
| Never-smokerc | 121 | 27 (22) | 94 (78) | 1 | 0.001 | 1 | NA |
| Ever-smokerd | 272 | 116 (43) | 156 (57) | 2.0 (1.3 – 3.1) | NA | ||
| Former-smokere | 132 | 50 (38) | 82 (62) | 1.8 (1.1 – 2.8) | 0.02 | 1.0 (0.6 – 1.7) | 0.9 |
| Current-smokerf | 140 | 66 (47) | 74 (53) | 2.2 (1.4 – 3.5) | < 0.0001 | 1.4 (0.8 – 2.3) | 0.24 |
| Site | |||||||
| Tongueg | 204 | 62 (30) | 142 (70) | 1 | 1 | ||
| FOMg | 76 | 37 (49) | 39 (51) | 2.0 (1.3 – 3.1) | 0.001 | 1.3 (0.8 – 2.1) | 0.22 |
| Soft palateh | 98 | 35 (36) | 63 (64) | 1.2 (0.8 – 1.8) | 0.36 | 0.7 (0.5 – 1.2) | 0.2 |
| Low-risk sitesi | 15 | 9 (60) | 6 (40) | 2.5 (1.3 – 5.1) | 0.01 | 1.7 (0.8 – 3.9) | 0.18 |
| TNM stage | |||||||
| Early | 287 | 83 (29) | 204 (71) | 1 | < 0.0001 | 1 | < 0.0001 |
| Late | 106 | 60 (57) | 46 (43) | 2.7 (1.9 – 3.8) | 2.4 (1.7 – 3.4) | ||
| Histology | |||||||
| Well-moderate | 371 | 131 (35) | 240 (65) | 1 | 0.24 | NA | NA |
| Poor | 22 | 12 (55) | 10 (46) | 1.4 (0.8 – 2.6) | |||
| Treatment | |||||||
| Surgery with or without radiation | 330 | 104 (32) | 226 (68) | 1 | < 0.0001 | 1 | 0.23 |
| Radiation | 63 | 39 (62) | 24 (38) | 2.2 (1.5 – 3.2) | 1.3 (0.8 – 2.1) | ||
Significant values, P < 0.05, are bolded.
HR: indicates a hazard ratio; CI: confidence interval.
Non-Caucasian; Asian, First Nation, Hispanic and more than one race.
Never smoker was defined as consumption of less than 100 cigarettes in life time.
Ever Smoker was defined as consumption of more than 100 cigarettes in life time.
Former smoker: Smokers who had stopped smoking after enrolling into the study.
Current smoker: Smokers who continued smoking after enrolling into the study.
Tongue and Floor of Mouth (FOM): are regarded high risk sites where oral premalignant lesions are at high risk of malignant transformation.
Soft palate: is regarded intermediate risk site where oral premalignant lesions are at an intermediate risk of malignant transformation.
Low-risk sites: Gingiva, vestibule, cheek, hard palate and labial mucosa.
Multivariate analysis was performed using multivariate Cox proportional hazard regression analysis across the different outcomes. Only increasing age and radiation treatment remained associated with local recurrence; increasing age, site (high or intermediate risk) and late stage were associated with lymph node metastasis; site (floor of mouth and soft palate) and late stage were associated with distant metastasis; increasing age, site (floor of mouth/soft palate), late TNM stages and radiation therapy were associated with death due to disease; and increasing age and late stages were associated with poorer overall survival.
6. Discussion
Our study results showed that oral SCC in the three age groups differed in many parameters, notably the habit of the patients, site, treatment and outcome of the SCCs.
Similar to previous studies, Young OSCC patients were more likely to be nonsmokers as compared to Traditional and Old groups. IARC working group has concluded that ‘in the oral cavity, there was sufficient evidence for the carcinogenicity of HPV 16 and limited evidence for the carcinogenicity of HPV 18’ (IARC, 2012, 2007). It is reasonable to hypothesize that HPV plays a more important role in the pathogenesis of oral SCC in younger people. However, there is a lack of study to show increased HPV infection in the oral cavity SCC from younger people. One study from the United States did show increased incidence of HPV-related oral SCC in younger patients [30].
Genetic susceptibility of young OSCC patients is another commonly held thesis as the etiology for OSCC in younger people. The lack of HPV infection and tobacco usage history in most young OSCC patients would support the hypothesis that the young oral SCC patients were genetically susceptible to oral cancer formation [31,32]. In a parallel thesis, old oral SCC patients could be less genetically susceptible than the traditional group since it took longer for oral SCCs to develop in the old group as compared to the traditional group. Interestingly, among the smokers, less than half of the smokers in Young and Traditional groups in our study quite smoking after the diagnosis of OSCC; whereas the majority of smokers in Old group quit smoking after the diagnosis.
Our results also showed that the three age groups showed significant differences in the location of the cancer: a significantly higher percentage of oral SCCs in the Young group were located on the tongue (85% in Young vs 46% and 47% in Traditional and Old groups), a significantly higher percentage of oral SCCs in the Traditional group were located in the floor of mouth (23% in Traditional vs 7% and 9% in Young and Old groups); and a significantly higher percentage of Oral SCCs in the Old group were located low-risk sites (42% in Old vs 7% and 26% in Young and Traditional groups).
The site predilection of cancer in the tongue is not only seen in young oral cancer patients, but also in non-smoker oral cancer patients, another population that possibly have genetic susceptibility to oral cancer. The basis for such site predilection remains unknown. The site predilection of oral cancer in the floor of mouth in the Traditional group could reflect the thesis that epithelium in the floor of mouth is thinner than the rest of the oral cavity, hence easier to penetrate to the basal epithelial cells, the target of the carcinogens, and the thesis that tobacco dissolved in saliva could expose the floor of mouth to carcinogens longer than the rest of the oral cavity. It is therefore surprising that there is such a low occurrence of oral SCC in the floor of mouth in the Old group, considering that most of oral SCCs in this group is smoking related. The site predilection of cancer in the low-risk sites in the Old group could be attributed to irritation from mastication/biting trauma in the cheek and labial mucosa or denture to the alveolar ridge and vestibular mucosa or periodontitis since inflammation and trauma would promote cancer development. This information is important for our screening of high-risk oral lesions for older patients, and we need to be vigilant not only for the floor of mouth and tongue areas, but also low-risk sites.
Oral SCCs in the Young group were more likely to be treated with surgery with or without radiation; whereas oral SCCs in the Old group were more likely to be treated with radiation alone, possibly owing to the general health of the patients. Compared to radiation therapy, surgery with or without radiation showed significantly lower rate of local recurrence and no statistical differences in the regional or distant metastasis. However, patients with radiation therapy seemed to have significantly higher mortality, either from the oral cancer or from other causes.
Young oral SCC patients fared consistently better than Traditional and Old age groups as judged by most outcomes (Tables 2, 3, 5 and 6). Traditional group fared better than Old age groups in mortality rate, either from the oral cancer or from other causes. It is quite possible that the better outcome from Young to Traditional to Old reflects the general health of the patients, with Young patients in the best health and Old patients the worst.
7. Conclusion
In conclusion, there are significant differences in OSCCs among the three age groups in various clinicopathological parameters, treatment and outcome. Understanding these differences should help the clinicians in the management of the disease.
8. Acknowledgement:
The authors want to thank Dr. Huijun Jiang for her assistance in data collection and statistical analysis. This work was supported by grants R01 DE13124 and R01 DE17013 from the National Institute of Dental and Craniofacial Research.
Footnotes
9. Conflict of Interest: None to declare.
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