Oral cancer among patients under the age of 35 years.EM Iype, M Pandey, A Mathew, G Thomas, P Sebastian, MK Nair
Department of Surgical Oncology, Epidemiology and Clinical studies, Community Oncology and Radiation Oncology, Regional Cancer Centre, Medical College, Thiruvananthapuram - 695 011, India. , India
Correspondence Address: Source of Support: None, Conflict of Interest: None PMID: 11832617
Source of Support: None, Conflict of Interest: None
BACKGROUND: Cancer of the oral cavity is one of the commonest cancers among males. AIMS: To assess the aetiological factors, patient characteristics, treatment and the outcome in young patients with oral cancer. SETTINGS AND DESIGN: A retrospective descriptive study of patients under the age of 35 years with cancer of the oral cavity treated between 1982-1996, with the last follow-up till 2001, using the tumour registry data of Regional Cancer Centre (RCC), Trivandrum, Kerala, India. SUBJECT AND METHOD: The detailed clinical, treatment and follow-up data were obtained from the computerised records of RCC and recorded on a preset proforma. This was analysed with emphasis on age, sex, risk factors, site, histology, clinical extent and treatment methods and survival in the study group. STATISTICAL ANALYSIS: The survival analysis was carried by Kaplan-Meier method and the difference in survival was analysed using log-rank test. RESULTS: Out of 264 patients analysed, tongue was the commonest site identified in 136 (52%) patients followed by buccal mucosa in 69 (26%) patients. A male female ratio of 2.3:1 was observed with a significantly higher male preponderance in buccal mucosa (4.3:1). Prior exposure to tobacco or alcohol was noted in 59.4% patients, with more habituÃ©s in buccal mucosa cancer. Histological confirmation was present only in 83.7% patients and among them most were squamous cell carcinoma (85.9%). Radiotherapy, surgery or combined modalities of treatment were employed for majority of patients. The 5-year survival was 57.3%. T stage of the tumour was found to be significant in predicting disease free survival (P=0.03). CONCLUSIONS: The importance of early detection for clinical down staging is stressed. There is a need to investigate the aetiology of intra oral cancers in younger patients since a significant proportion (almost 40%) of these patients do not have associated risk factors for cancer.
Keywords: Adult, Carcinoma, Squamous Cell, epidemiology,pathology,therapy,Female, Follow-Up Studies, Human, India, epidemiology,Male, Mouth Neoplasms, epidemiology,pathology,therapy,Retrospective Studies, Risk Factors, Survival Analysis, Time Factors,
Oral cancer is the sixth most common cancer in the world. It is a major oncological problem in the regions of the world where tobacco habits in the form of chewing and/or smoking with or without alcohol intake are common. It typically occurs in the elderly men during the fifth through eighth decade of life and is rarely seen in young people. Oral cancer represents 14% of all cancer cases at Regional Cancer Centre (RCC), Kerala, India. It constituted 17% of all cancers in males and 10.5% of all cancers in females making it the commonest cancer in males and the third commonest cancer among females.
The incidence of oral cancer in young adults ranges between 0.4% and 5.5%., As the disease is uncommon before the age of 35 years little is known about its aetiology, natural history and optimal therapeutic management. Even though tobacco and alcohol abuse are said to be the main aetiological factors, it is reported only for a very small percentage of young patients in the earlier series. The lack of significant habits in young patients have prompted many to postulate factors like immune deficiency, genetic factors and dietary factors in the aetiology of these cancers. Viruses like herpes simplex virus and human papilloma virus have also been proposed to be contributing factors. Literature suggests that oral cancers in young patients show a general trend of aggressive course and poor prognosis. We carried out this study to define the clinical and pathological features, the treatment methods adopted and the outcome among young patients with oral cancer.
A retrospective analysis of the patients under the age of 35 years with oral cancer presented at RCC, Trivandrum between 1982-1996, was carried out. Data extraction was carried from electronic database of RCC by the ICD - codes for site and age < 35 years. The anatomical sites reviewed in this study included lip, buccal mucosa, upper and lower alveolus, hard palate, anterior 2/3 of tongue and floor of mouth. Variables analysed for each patient included age, sex, history of tobacco and alcohol abuse, history of any cancer in the first-degree family members, presence of premalignant lesions, histology, clinical extent and lymph node involvement at the time of presentation. The patients were staged according to the American Joint Committee on Cancer (AJCC) staging system. All patients were evaluated for the treatment employed. All variables were entered in a database for analysis. The Kaplan-Meier method was used to calculate the overall and disease free survival and log rank test was used for comparing survival curves.
A total of 264 patients under the age of 35 years with oral cancer in the 15-year period from 1982-1996 were retrospectively analysed. Tongue was the commonest site identified in 136 (52%) patients followed by buccal mucosa in 69 (26%), alveolus in 26 (10%), palate in 12 (4.5%), lip in 6 (2.3%), floor of mouth in 5 (1.9%) and other intraoral non-specified sites in 10 (3.8%).
There were 184 (70%) males and 80 (30%) females, with a male to female ratio of 2.3:1. The significantly highest male preponderance was noted in patients with cancer of buccal mucosa (4.3:1). Among these patients Hindus constituted 59%, Christians 25.8% and Muslim 13.3%. The distribution was similar in the case of different sub sites. The mean age at presentation was 30.7 years (SD+5). The presentation of tongue cancer was slightly earlier compared to buccal mucosa cancer. Forty-four % of cases of carcinoma-tongue presented below 30 years compared to 27.5% of carcinoma of buccal mucosa.
Family history of cancer was present in 23 (9%) patients while family history of oral cancer was present in 9 (3%) patients. Precancerous lesions in the form of leukoplakia, sub mucous fibrosis, lichen planus and erythroplakia were present in 35 (11%) patients. More than half of the patients 149 (56.4%) were habituated to either tobacco chewing, smoking or alcohol. About 67 (49%) of tongue cancer patients and 55 (79.7%) patients with buccal mucosa cancer were habitués [Table - 1].
Histological confirmation was present in 221 (83.7%) patients. Squamous cell carcinomas (SCC) were the commonest, in 190 (72%) patients; tumours of the minor salivary gland were seen in 10 (3.8%) patients, 5 (1.9%) had soft tissue sarcomas and 16 (6%) had non-specific malignancies. In 43 (16.3%) patients, no attempt for histological confirmation had been made due to very advanced nature of the disease. Among the squamous cell carcinoma 100 (52.6%) were well-differentiated tumours, 65 (34.2%) were moderately differentiated and 8 (4.2%) were poorly differentiated tumours. For 17 (8.9%) patients, the degree of differentiation was not recorded.
Most of the cases of oral cancer presented in advanced stage. At the time of presentation 66.3% were in stage III and IV. Among buccal mucosa cancers, 68% were in advanced stages and among tongue cancer 62.5% were in advanced stages. Regional node involvement was seen in 51.9%, with 81 patients in N1 Stage, 35 in N2 while 21 in N3 stage. [Table - 2]
Majority of the patients were treated with radiotherapy (RT) as the primary modality. It was employed in 96 (36.6%) patients as the only modality. Radiation followed by surgery was performed in 21 (8%) patients and in combination with chemotherapy it was used in another 38 (14.3%) cases. Surgery and postoperative radiation was employed in 45 (17%) patients and a small group of 21 (8%) patients was treated by surgery alone [Table - 3].
After the completion of treatment 99/221 patients (44.8%) had residual disease and 63/221 patients (28.3%) developed recurrence. Among the recurrences 21 were in the primary site, 18 had nodal recurrence and 18 developed loco-regional recurrences. Two patients had second primary, while four developed distant metastasis [Table - 4]. For the recurrent lesions, surgery and radiation treatment either alone or in combination was employed in 73.3% and palliative treatment was given to 27% patients. At the last follow up, 99 out of 221 patients treated (44.8) were alive without any evidence of disease, 36 (16.3) were dead while 86 (38.9%) were alive with disease, undergoing further treatment [Table - 5].
The overall disease free survival (DFS) in this study group at 3 and 5 years was 66% and 57.3% respectively. Males had an apparently better DFS compared to females (59.5% and 41.5% respectively at 5 years). Lip cancer patients had a 100% DFS at 5 years whereas it was 61.9% for buccal mucosa and 17.4% for tongue. Patients with early stage disease at presentation had better survival [Table - 6]; the difference was statistically significant (P=0.03).
Oral cancer in young patients under 35 years forms about 2.8% of all cases of oral cancer seen at RCC, Trivandrum in the present series, while it is between 0.4 and 5% in Western series., There is an overall male predominance in all intraoral sub-sites as seen in most of earlier studies. But some have reported a female predominance in younger age group,, including an earlier comparative study of oral SCC from our institution.
Oral tongue was the most common site in the present series constituting 52% of all cases followed by buccal mucosa, which formed 26%. This is in contrast to the earlier report on all oral cancer cases from our centre, where buccal mucosa cancers outnumbered the tongue cancer (49.9% and 23.9% respectively). Only about half of the cases in this series were addicted to tobacco and alcohol compared to 99% of habitués in the older population in the earlier series. The number of habitués was higher in buccal mucosa cancer (79.7%) compared to tongue cancer (49%). This may point to the fact that tobacco habits are a major determinant of buccal mucosa cancer compared to tongue cancer; the latter seemed to have a different aetiology at younger age.
Some authors have suggested that cancer in young adults tends to be more frequently anaplastic resulting in a more aggressive behaviour and poor prognosis. According to Holm et al the morphological grade of the oral cancer does not correlate with survival and relapse-free periods. Histopathological grading of tumours in this study showed that the majority of the tumours were well differentiated. The proportion of advanced cases in the present series was considerably higher than reported earlier. At the time of presentation 66.3% cases were in advanced stages (III and IV) and 51.9% patients had regional lymph node involvement. More advanced stage lesions were seen in buccal mucosa cancer compared to tongue cancer.
Analysis of the response of the tumours to treatment revealed that 73% developed loco-regional failure and 15.8% died secondary to their cancer compared to 57% failure and 47% death due to cancer in young tongue cancer patients in earlier series. Review of the literature indicates conflicting reports of survival rates in younger age groups. We found no statistically significant differences in survival between males and females, and between different subsites. However, early stage disease had a significantly better survival than advanced disease in the present series.
The result of the present study demonstrates an almost similar survival in young oral cancer patients compared to older counter parts. As the results are good in early stages of the disease, the need for early detection and clinical down staging should be stressed. More in-depth studies are needed to investigate the aetiology of intraoral cancer in younger patients. Any ulcer or lesion at a younger age should not be dismissed easily, even if it is not habit related. High index of clinical suspicion in high incidence areas should lead to further investigation in order to identify the disease in early stage, which is perhaps the only way to ensure good prognosis.
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4][Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5], [Table - 6]