There is growing interest in non-smoking non-drinking (NSND) patients presenting with oral squamous cell carcinoma (OSCC). There are, however, few published reports of OSCC in the elderly. We describe a subgroup of elderly NSND patients presenting with OSCC. Patients with SCC of the oral cavity were retrospectively assessed from the Head and Neck Oncology Tumour Stream database of the Royal Melbourne Hospital. Epidemiological and clinical data for 169 consecutive patients were reviewed and analysed. NSND patients were more likely to be females with a higher median age at presentation. They were more likely to have maxillary alveolus tumours and oral tongue tumours, with retromolar or mandibular tumours less likely. Second primary tumours for this subgroup were confined to the oral cavity. NSND elderly females experienced a worse disease-specific mortality. We have identified a distinct subgroup of elderly female patients presenting with OSCC not associated with the traditional risk factors of tobacco and alcohol, who have a worse prognosis. Altered management algorithms may prove beneficial for these patients, and further investigation and genetic analysis are required to delineate the aetiology of these carcinomas.
Oral squamous cell carcinoma (OSCC) is the seventh most prevalent malignancy globally, resulting in significant mortality and morbidity, with severe impairment of quality of life. While tobacco and alcohol are well established aetiological agents for the development of OSCC, non-smoking, non-drinking patients (NSND) presenting with OSCC have been identified in the literature as a unique and growing subgroup. In contrast to the general predilection for males in OSCC, the NSND group has a female preponderance, younger mean age, and the carcinoma is more likely to be in the oral cavity than at other sites. The NSND population currently represents 13–35% of the OSCC population, although this proportion may increase as tobacco use decreases.
There has been considerable interest in young female NSND presenting with OSCC. The human papillomavirus (HPV), in particular HPV-16, has been implicated in oropharyngeal SCC in young NSND patients. The role of HPV in OSCC and indeed implications for clinical behaviour is uncertain.
There are few published reports of oral cancer in elderly NSND patients. The proportion of elderly patients is increasing alongside life-expectancy, with as many as 24% of head and neck cancers found in patients over 70 years old. The aetiology of OSCC in this NSND elderly population is as yet unknown and management algorithms may be different for this age group.
This retrospective review was undertaken to compare OSCC disease characteristics between NSND elderly females and the rest of the population.
Materials and methods
One hundred and sixty-nine consecutive patients presenting with new or recurrent OSCC between January 2007 and July 2010 were reviewed. Carcinomas of the lip were excluded. Clinical and epidemiological data were obtained from the BioGrid ACCORD head and neck tumour database. This prospectively collected database contains information on risk factors, tumour pathology, subsite, staging, and treatment. Further information was obtained from the clinical history.
Patients were classified as NSND or SD (smokers and/or drinkers). Non-smoking status was defined as a negligible history of tobacco use and non-drinking status as nil regular alcohol consumption with no previous history of heavy alcohol intake or abuse. Tumours were classified according to the International Classification of Diseases (ICD) for oral cavity subsites and retrospectively updated to reflect the American Joint Committee on Cancer (AJCC) sixth edition system. Second primary tumours and recurrences were classified as described by Warren and Gates.
Mortality data were sourced from both the ACCORD and the Victorian Cancer Registry databases, with a minimum follow-up of 18 months (census date 1 January 2012), including disease-specific mortality. Disease-free survival was recorded from the clinical follow-up notes.
A statistical analysis was performed to directly compare the NSND and the SD groups using the software package IBM SPSS Statistics 19. χ 2 Tests were employed for disease characteristics and demographics, while Student’s t -tests were utilized for age analysis. Survival data were plotted on Kaplan–Meier curves with log-rank tests used for statistical analysis. Statistical significance was set at P < 0.05.
A total of 41 patients (24.3%) were identified as NSND from 169 consecutive patients presenting with OSCC between January 2007 and July 2010 ( Table 1 ). The mean age at presentation for all patients was 65.5 years; 72 patients (42.6%) were female. There were no regular users of smokeless tobacco (snus, snuff, etc.) or other oral carcinogens (areca nut, betel quid). Sixty-nine patients (40.8%) were non-smokers and 58 patients (34.3%) were non-drinkers.
|SD ( n = 128) n (% of total SD)||NSND ( n = 41) n (% of total NSND)|
|Male * ( n = 97)||87 (68.0)||10 (24.4)|
|Female * ( n = 72)||41 (32.0)||31 (75.6)|
The NSND group had a mean age of 71 years (median 73 years), and the SD group had a mean age of 63 years (median 63 years) ( t -test, P < 0.05). A bimodal age distribution was noted in the NSND group, with peaks at 50–59 years and 70–79 years. In contrast, a single peak at 60–69 years was seen in the SD group ( Fig. 1 ).
Maxillary alveolus tumours were more common in the NSND group than in the SD group ( χ 2 = 4.92, df = 1, P < 0.05), while retromolar tumours were more common in the SD group than in the NSND group ( χ 2 = 5.58, df = 1, P < 0.05). Whilst there were larger numbers of NSND patients with oral tongue tumours, there was a trend towards mandibular alveolus tumours in the SD group ( Table 2 ).
|SD, n (% of total SD)||NSND, n (% of total NSND)|
|Tongue ( n = 72)||51 (39.8)||21 (51.2)|
|Retromolar ( n = 27) *||25 (19.5)||2 (4.9)|
|Floor of mouth ( n = 22)||18 (14.1)||4 (9.8)|
|Maxillary alveolus ( n = 20) *||12 (9.4)||8 (19.5)|
|Mandibular alveolus ( n = 7) †||7 (5.5)||0 (0)|
|Buccal mucosa ( n = 15)||10 (7.8)||5 (12.2)|
|Hard palate ( n = 6)||5 (3.9)||1 (2.4)|
There was no statistically significant difference in TNM staging, histological subtype, or differentiation between the two groups (NSND and SD) ( Table 3 ). Tumours were relatively evenly staged as T1, T2, and T4, with a smaller percentage of tumours staged as T3. Forty-one patients (24.3%) presented with nodal disease. No patients had distant metastatic disease at the time of presentation.
|SD, n (%)||NSND, n (%)|
|Stage I/II||73 (57.0)||25 (61.0)|
|Stage III/IV||55 (43.0)||16 (39.0)|
Thirteen patients, of whom five were NSND, presented with a second primary tumour during the follow-up period (7.7%), while six patients presented with recurrent disease (3.6%). Two patients (1.2%), both of whom drank heavily and had in excess of a 30 pack-year history of tobacco, presented with synchronous tumours ( Table 4 ). Two of the five NSND patients had multiple presentations with second primary tumours, in contrast to none of the SD patients.
|Patient *||Original primary site||Second primary site||Interval (years)|
|NSND||1||Floor of mouth||Tongue||25|
|2||Mandibular alveolus||Mandibular alveolus||11|
|3||Retromolar trigone||Hard palate||7|
Retromolar trigone mandible
|Buccal mucosa||5 From most recent previous primary|
|5||Retromolar trigone (L) maxillary alveolus||(R) maxilla||2 From most recent previous primary|
|7||Mandibular alveolus||Mandibular alveolus||9|
|10||Mandibular alveolus||Floor of mouth||16|
|11||Floor of mouth||Retromolar trigone||1|
|12||Floor of mouth||Tongue||29|
|15||Tonsillar pillar||Retromolar trigone||0|