Abstract
Purpose
To examine the relationship between tobacco smoking history and the clinicopathologic and survival characteristics of patients with oral cavity squamous cell carcinoma (OCSCC).
Materials and methods
This is a retrospective review of 531 patients treated for OCSCC from January 1998 to December 2009 at a tertiary care medical center.
Results
Thirty-two percent of OCSCC patients were never smokers. There were significant differences in tumor location between ever smokers and never smokers (p < 0.001), with never smokers more likely to have oral tongue tumors. Smokers were significantly (p < 0.001) more likely than never smokers to present with locally advanced (T3 or T4) disease (57.8% vs. 35.4%). Never smokers demonstrated improved overall survival (78.8 months in never smokers vs. 44.7 months in ever smokers, p = .03). However, there were no survival differences when the two groups were compared separately for locally early (T1/T2) or advanced (T3/T4) disease. For T1/T2 tumors, mean survival was 88.2 months for never smokers and 78.5 months for smokers (p = .10). For T3/T4 tumors, median survival was 29.1 months for never smokers and 23.8 months for smokers (p = .09).
Conclusions
Primary tumor location and T-status in OCSCC differed between never smokers and smokers. Compared to smokers, never smokers had fewer locally advanced tumors and better overall survival.
1
Introduction
Five percent of all malignancies occur in the head and neck, and approximately half of those occur in the oral cavity . Oral cavity squamous cell carcinoma (OCSCC) is the eighth most common malignancy worldwide, with more than 300,000 new cases annually.
The most common risk factors for head and neck squamous cell carcinoma (HNSCC) are tobacco and alcohol abuse . OCSCC has typically been associated with men aged 60 years and older with an extensive history of tobacco and/or alcohol use; however, this patient demographic is changing . According to the U.S. National Health Interview Survey, the prevalence of cigarette smoking has markedly decreased among Americans since the mid-1960s and alcohol use has declined since the 1970s . Recently, there has been an increase in the number of never smokers who are developing OCSCC . The development of OCSCC in never smokers is thought to differ from the carcinogenesis mechanisms typically associated with smoking-related malignancies, possibly involving unique genetic cancer susceptibility mutations or as yet unknown environmental or viral pathogens.
Several studies have evaluated the clinical characteristics of HNSCC in never-smokers , but only a few studies have focused specifically on OCSCC . The data are conflicting with regards to the frequency of never smokers and their age at tumor presentation, with some studies indicating that never smokers present at a younger age and others suggesting that they present later in life . The data also differ on survival rates of never smokers compared to smokers.
The purpose of the present study was to examine the relationship between tobacco smoking history and the clinicopathologic and survival characteristics of OCSCC. By describing the clinical characteristics of OCSCC in never smokers, we seek to better define this unique subset of patients and ultimately aid in the prevention, diagnosis, and management of this disease.
2
Materials and methods
This study was approved by the Committee on Human Research at the University of California, San Francisco. All adult subjects with newly diagnosed OCSCC treated initially with surgery at the University of California, San Francisco between 1/1/1999 and 12/31/2009 were retrospectively identified by querying the institutional otolaryngology database for all oral cavity cancer ICD9 codes and by querying the institutional tumor registry for oral cavity carcinoma. Patients with non-squamous histology, those who had no documentation of smoking status in the medical chart, those not treated surgically, and those who received any prior treatment (surgery, chemotherapy, or radiation) were excluded from the study.
Clinical and pathologic data were abstracted from the paper charts, electronic records, and the tumor registry database. Patients were considered to be smokers if they reported a greater than 100 cigarette lifetime smoking history; all others were considered never smokers. All staging was based on the American Joint Committee on Cancer (AJCC) 7th edition. Site of presentation was evaluated based on 6 oral cavity sites: oral tongue, floor of mouth, alveolar ridge, retromolar trigone, buccal mucosa, and hard palate. Recurrence and survival times were calculated from the date of initial surgical intervention to the date of last follow-up or death.
Descriptive statistics were calculated, with mean and standard deviation reported for all continuous variables. To compare differences between ever and never-smokers, two-sample t-tests were performed for continuous variables, and chi-squared analyses were performed for categorical variables. Survival analysis was performed using Kaplan–Meier method. All survival analysis was performed using XLSTAT Software (Addinsoft, New York, NY). A multivariate analysis was performed using the Cox proportional hazards model to assess prognostic factors affecting survival. P values < 0.05 were considered statistically significant.
2
Materials and methods
This study was approved by the Committee on Human Research at the University of California, San Francisco. All adult subjects with newly diagnosed OCSCC treated initially with surgery at the University of California, San Francisco between 1/1/1999 and 12/31/2009 were retrospectively identified by querying the institutional otolaryngology database for all oral cavity cancer ICD9 codes and by querying the institutional tumor registry for oral cavity carcinoma. Patients with non-squamous histology, those who had no documentation of smoking status in the medical chart, those not treated surgically, and those who received any prior treatment (surgery, chemotherapy, or radiation) were excluded from the study.
Clinical and pathologic data were abstracted from the paper charts, electronic records, and the tumor registry database. Patients were considered to be smokers if they reported a greater than 100 cigarette lifetime smoking history; all others were considered never smokers. All staging was based on the American Joint Committee on Cancer (AJCC) 7th edition. Site of presentation was evaluated based on 6 oral cavity sites: oral tongue, floor of mouth, alveolar ridge, retromolar trigone, buccal mucosa, and hard palate. Recurrence and survival times were calculated from the date of initial surgical intervention to the date of last follow-up or death.
Descriptive statistics were calculated, with mean and standard deviation reported for all continuous variables. To compare differences between ever and never-smokers, two-sample t-tests were performed for continuous variables, and chi-squared analyses were performed for categorical variables. Survival analysis was performed using Kaplan–Meier method. All survival analysis was performed using XLSTAT Software (Addinsoft, New York, NY). A multivariate analysis was performed using the Cox proportional hazards model to assess prognostic factors affecting survival. P values < 0.05 were considered statistically significant.
3
Results
A total of 531 patients (311 males and 220 females) were identified who met the inclusion criteria for this study. Their demographics and tumor characteristics are summarized in Table 1 . Follow-up varied from 6 to 133 months for living patients. Mean follow-up as of April 1, 2012 was 36 months. Of all patients, 172 (32.4%) were never smokers and 359 (67.6%) reported a history of current or prior tobacco use with an average of 39 pack-years. Overall, the most common tumor location was oral tongue (44%) followed by floor of mouth (19%).
| Factor | No. of patients (%) |
|---|---|
| Median age at diagnosis | 61.31 |
| Sex | |
| Male | 311 (59%) |
| Female | 220 (41%) |
| Ethnicity | |
| Caucasian | 416 (78%) |
| Asian | 64 (12%) |
| African American | 23 (4%) |
| Other | 15 (3%) |
| Unknown | 13 (2%) |
| Smoking Status | |
| Current | 181 (34%) |
| Prior | 178 (33%) |
| Never | 172 (32%) |
| Primary tumor site | |
| Oral tongue | 234 (44%) |
| Floor of mouth | 103 (19%) |
| Gingiva | 72 (14%) |
| Retromolar Trigone | 53 (10%) |
| Buccal | 29 (5%) |
| Hard Palate | 23 (4%) |
| Alveolar Ridge | 17 (3%) |
| T classification | |
| In-situ | 10 (2%) |
| T1 | 135 (25%) |
| T2 | 126 (24%) |
| T3 | 49 (9%) |
| T4 | 143 (27%) |
| Unknown | 68 (13%) |
| N classification | |
| N0 | 284 (53%) |
| N1 | 53 (10%) |
| N2 | 102 (19%) |
| N3 | 2 (< 1%) |
| Unknown | 90 (17%) |
| Treatment Characteristics | |
| Adjuvant radiation therapy | 202 (38%) |
| Adjuvant chemotherapy | 42 (8%) |
| Neck Dissection at time of initial surgery | 430 (81%) |
Table 2 summarizes the clinicopathologic and treatment characteristics of the ever smoker population compared to the never smokers. The average age at diagnosis of ever-smokers was 61.4 years, and the average age of never-smokers was 61.0 years. Never-smoking patients were more likely to be women. Ethnicities were also significantly different between the ever smokers and never smokers. The never smokers were less likely to be African American and more likely to be Asian than smokers. The distribution of tumor location within the oral cavity also varied significantly between the ever smokers and never smokers. More than half (55%) of never smokers had tumors of the oral tongue. The ever smokers were also most likely to have tumors of the oral tongue (38.7%), followed by floor of mouth (26%). There was no difference in nodal status between ever smokers and never smokers. There was a significant difference in T status (p < 0.001), with never smokers more likely to have early (T1–T2) disease and smokers more likely to have advanced (T3–T4) disease.
| Factor | Ever Smokers | Never Smokers | p value |
|---|---|---|---|
| No. of patients | 359 | 172 | |
| Median age at diagnosis | 61.4 | 61.0 | 0.78 |
| Sex | < 0.001 | ||
| Male | 232 (64.6%) | 79 (46%) | |
| Female | 127 (35.4%) | 93 (54%) | |
| Ethnicity | < 0.001 | ||
| Caucasian | 287 (80%) | 129 (75%) | |
| Asian | 29 (8.1%) | 35 (20.3%) | |
| African American | 22 (7.6%) | 1 (0.6%) | |
| Other | 11 (3.1%) | 4 (2.3%) | |
| Unknown | 10 (2.8%) | 3 (1.7%) | |
| Smoking Status | < 0.001 | ||
| Current | 181 (50.4%) | 0 (0%) | |
| Prior | 178 (49.6%) | 0 (0%) | |
| Never | 0 (0%) | 172 (100%) | |
| Primary tumor site | < 0.001 | ||
| Oral tongue | 139 (38.7%) | 95 (55%) | |
| Floor of mouth | 93 (26.0%) | 10 (5.8%) | |
| Alveolar Ridge | 56 (15.6%) | 33 (19.2%) | |
| Retromolar Trigone | 42 (11.7%) | 11 (6.4%) | |
| Buccal | 14 (3.9%) | 15 (8.7%) | |
| Hard Palate | 15 (4.2%) | 8 (4.7%) | |
| T classification | < 0.001 | ||
| In-situ | 6 (1.7%) | 4 (2.3%) | |
| T1 | 89 (24.8%) | 56 (32.6%) | |
| T2 | 20 (5.6%) | 48 (27.9%) | |
| T3 | 34 (9.5%) | 19 (11.0%) | |
| T4 | 115 (32.0%) | 38 (22.0%) | |
| Unknown | 14 (3.9%) | 15 (8.7%) | |
| N classification | 0.29 | ||
| N0 | 190 (52.9%) | 94 (54.6%) | |
| N1 | 35 (9.7%) | 18 (10.5%) | |
| N2 | 77 (21.4%) | 25 (14.5%) | |
| N3 | 2 (0.6%) | 0 (0%) | |
| Unknown | 55 (15.3%) | 35 (20.3%) | |
| Treatment characteristics | |||
| Adjuvant radiation therapy | 151 (42%) | 51 (30%) | 0.160 |
| Adjuvant chemotherapy | 32 (9%) | 10 (6%) | 0.499 |
| Neck Dissection at time of initial surgery | 305 (85%) | 125 (72%) | 0.218 |
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