- Citado por SciELO
- Citado por Google
- Similares en SciELO
- Similares en Google
versión On-line ISSN 1698-6946
Med. oral patol. oral cir.bucal (Internet) vol.12 no.7 nov. 2007
Gonçalo Seguro Dias, Arlindo Pereira de Almeida
Oral Medicine Department, School of Dentistry, Lisbon University, Lisbon, Portugal
Cancer is the second cause of death in Portugal right after cardio vascular diseases. In Portugal the incidence of oral and pharynx cancer (OPC) is higher than uterus and larynx cancers, and in US its frequency is higher than melanoma or uterus cancer, diseases that concern more population than oral cancer.
Aims. The aim of this paper is to identify preferable anatomic location for oral cancer, mean age of patients, the use of tobacco and alcohol, histological characteristics, staging, type of therapeutics, presence of metastases and 1 and 5 year follow up.
Matherials and Methods. Data was collected from clinical charts of 365 cases from the Centro de Lisboa do Instituto Português de Oncologia with histological confirmation of malign tumor of the mouth. These cases are the total of oral malign tumors in the years of 1997, 1998 and 1999 in that institution.
Results. We observe that despite modern diagnostic and treatment techniques 37,9% of all patients died after first year with evidence of tumor. From all patients just 23,7% were free of disease after 5 years of treatment. Tongue was the principal region affected and the average age was 62, 25 years. It was concluded that 57, 8% of patient were smokers and 43,8% were alcohol drinkers. A high number of patients were submitted to radiotherapy either alone or with other treatment options.
Key words: Oral cancer, epidemiology, squamous cell carcinoma.
Cancer is the second cause of death in Portugal, right after cardiovascular diseases (CVD), and head and neck cancer accounts for 10% of all malign cancers. In Portugal the incidence of oral and pharyngeal cancer (OPC) is higher than uterus and larynx cancers, and in United States estimated deaths for this cancer are higher than melanoma or uterus cancer, which are more concerning diseases than OPC for population in general, even if OPC has severe consequences, not only functional but also psychologically (1-2).
The death rate for OPC in males starts to rise in mid eighties. Between 1988 and 1998 and an increase of 24% was noticed compared to earlier years. This increase affected mainly middle age and young males following a pattern where the incidence age was decreasing (3-5).
Trends in oral cancer incidence rates that include all oral sites may be misleading. For example, risk factors for lip cancer are different from intraoral sites. Also because there are differences in oral cancer incidence rates by age, anatomic site, treatment and geographic location (6-10). Thus, descriptive oral cancer data for each geographic area are important to understand the extent of the problem (11-13). The purpose of this study is to analyze a large case series of oral cancer emphasing risk factors and outcome.
Materials and Methods
A total of 365 files with a histopathological diagnosis of primary malignant neoplasm of the mouth were reviewed. Data collected from patient records included patient gender, anatomic location (buccal mucosa, tongue, floor of the mouth, gingival and palate)(ICD-O, International Classification of Disease- Oncology)(14), pre-treatment staging, treatment options, metastases evidence, recurrence, 1 and 5 year follow-up, tobacco and alcoholic habits, association with other tumours of the upper aero digestive tract and outcome. Lip cancer was not considered because it has different risk factors. Descriptive analyses of the variables was made using software SPSS for windows.
Information on alcohol consumption included the type of alcoholic beverage. Taking into account the different alcohol concentrations for each beverage, we considered someone with alcoholic habits who drunk more than 12 g of ethanol a day. At the some time a smoker was define as someone who smoke more than a cigarette a day for more than a year.
Epidemiological research concerning oral cancer is complex due to the existence of multiple anatomic regions and sub-regions. The anatomic location was identified by anatomic sub-regions whenever possible. All results show frequency of each variable.
Eighty percent of the 365 oral cancer cases was diagnosed in males. The overall male-to-female ratio was 4.0. The average age of diagnosis of malignant neoplasm was 62 years old with a standard deviation of nearly 12 years.
Anatomic location was registered and coded according to the recommendations of the ICD-O (International Classification of Disease Oncology). The anatomic location distribution indicates that the tongue and its sub-regions (C01.9 to C02.9) were involved in about 43% of the cases. Other sites with significant results were: floor of the mouth and its sub-regions (C04.0 to C04.9) with approximately 18,9%; palate (C05.0 and C05.1) with about 6,9%; gum(C03.0 and C03.1) and retromolar pad(C06.2) with 6,6%, and oral mucosa (C06.0) with 6,0% (Table 1).
Lesions involving overlapping regions (C06.8) total 12,3% of the malignancies, what indicates that sometimes due to a late diagnosis its difficult to determinate the original location of the tumour.
The distribution of the tumour histological types is shown in table 2. Squamous Cell Carcinomas SCC (Non Otherwise Specified = NOS) were the most common type. Non-epithelial tumours were less than 3% of all malignant neoplasms (8000.3 and 9591.3).
We found that 84,6% of the tumours were SCC (NOS) and that percentage is even higher when considering both the non-keratinized and keratinized spinocellular carcinomas (table 2).
The majority of the tumors were well differentiated 36,2%. However, the analysis of this variable was not possible in 30,1% of the cases.
Most of oral cancers were diagnosed at advanced stages (T3 and T4) - 48,2% . Lymph node involvement (N) regardless of the tumour size was 40,6%.
Distant metastases were identified in 38 cases which represents 9,3% of the overall sample. The mean time for distant metastasis identification after the diagnosis was 496 days. Distant metastases affected mainly the lung. This organ stands for 47,4% of all the anatomical locations with metastases involvement.
Combined radiation and surgery was provided to 20,8% of the cases. The radiation therapy alone, or combined with surgery or chemotherapy was provided to more than 60%. Radiation therapy included patients treated both with curative or palliative intent.
Clinical or histopathological evidence of recurrence was registered in 22,5% of the cases. Recurrence was not possible to be identified in 31,1% of the subjects due to follow up absence or late diagnosis (in some cases patients were never free of disease, being impracticable to identified recurrence).
At 1 year follow up, of all the cases studied, approximately 36,4% of the patients had deceased with documented tumour, while 38,9% exhibited no such evidence (Table 3). Regardless of the clinical condition about 58,9% of the patients were alive. At 5 year follow up, 26,5% of all the sample cases were disease-free five years after treatment completion. Regarding only the individuals who were alive after the first year follow-up the disease-free group at the fifth year rises to 45,1% (Table 4). A high percentage of cases, 33,6%, were included in a non-applyable category. (These included the patients already dead and the ones that miss follow up appointments).
Of the total sample 57,8% had tabagic habits and 47,9% reported alcoholic habits. To notice is the fact that 43,8% of the patients had both habits.
In 25 cases an association with other primary tumours was established, which represents of 6,8% of the sample. The main regions affected were the larynx and the lungs with percentages of 40% and 16%, respectively.
This non-randomized sample is the totality of oral cancer cases diagnosed between 1997 and 1999 at Francisco Gentil Lisbon Centre of Portuguese Institute of Oncology (Centro de Lisboa do Instituto Português de Oncologia Francisco Gentil). We examined the available records of all patients with oral cancer.
This research indicates that 80% of cases affected males. This finding is consistent with other oral cancer demographic reports(2,3,5).However gender is not a risk factor per se for oral cancer. This prevalence indicates the existence of other risk factors associated to the male gender, such as tabagic and alcoholic habits.
The most frequent anatomical location was the tongue. This is supported by other studies that showed the tongue as the main organ involved, when excluding the lip regions(15-17). The existence of approximately 11% tumours involving overlapping regions, 74,3% of which are stage T4 is indicative of late diagnosis.
The patients average age of 62,2 years-old along with the standard deviation of approximately 12 years were consistent with other reports in general, and confirms the suggestion to adopt screening appointments for patients with certain risk factors. Based on our results, screening appointments targeted to individuals over 50 years old and/or alcohol consumers could raise the number of early diagnosis and therefore increase treatment outcome. Moreover, monitoring pre-malignant lesions may also contribute to early diagnosis of SCC(5). Our research indicates that the most frequent histopathological type of oral tumour is SCC (84,1%) which corroborates other studies findings (18).
Despite the progress in diagnosis and treatment of oral cancer the survival rates are lower in comparison to other types of cancer. This may be related to late diagnosis in the majority of cases. In our report, T3 and T4 tumours were extremely high 50% and the involvement of regional lymph nodes were present in 40,6% of the patients. Once that lymph nodes involvement is an oral cancer prognosis sign, histological analysis of the sentinel node may provide specific information about ganglia involvement circumventing the limitations of clinical and imaging methods (19-20).
In our sample a great number of patients received radiation treatment. Once that radiotherapy is planned to be used in a great number of patients, a pre-treatment evaluation should be undertaken in order to apply preventive measures to minimize collateral effects (21-22).
At 1 year follow-up 40% of the patients were disease-free. This finding is similar to other authors studies(23). Our 5 year follow-up indicates that the percentage of disease-free patients, 26,5%, is not as high as in other reports(16-18). These low results may be explained by the fact that our sample is from an oncological hospital, where many patients are referred to palliative treatment for advanced tumours and also because part of the population has no primary oral care assistance.
The majority of patients in this study had a history of tobacco use - 57,8%. The positive association between oral cancer and tobacco use is well documented by various authors who have shown that the risk of developing oral cancer is directly proportional to the number of cigarettes smoked per day and to the number of years as a smoker (24-25).
Alcohol consumers were approximately 50% of the total number of cases. The association between oral cancer and alcohol consumption may be explained in Portugal because it is one of the countries with the highest average alcohol consumption, namely 12,1 litres (25,57 U.S. pints) of pure alcohol per capita(26). Although it seems that alcohol is not a carcinogen per se, once it is metabolised active substances with carcinogenic potential are produced (27).
The interaction between alcohol and tobacco has been studied in order to determine the existence of a synergic mechanism predisposing to oral cancer. We found that 43,8% of the patients were both alcohol consumers and smokers. Excess risk of approximately 10 fold is associated with tobacco and alcohol use. Nowadays it is proposed that tobacco is an initiator while alcohol is a promoter, presumably by either increasing the permeability of mucosa lining cells to tobacco carcinogens or by cellular lesions induced directly by alcohol metabolism (28). Therefore primary prevention must favour a decrease in exposure to tobacco, alcohol and other carcinogenic agents.
The highest incidence of second tumours is found in the larynx and lung, which is in accordance with other authors reports (29-30). However, our total percentage is lower, namely 6,1%. This might be explained by the difficulty in distinguishing between two primary tumours.
Metastatic spread of oral SCC tends to increase with the size of the primary tumor. Metastases were observe after an average time of 16,5 months. Therefore, within this timeframe clinical surveillance of patients with SCC must be scheduled in regular intervals in order to identify metastases.
Because of the magnitude of the oral cancer problem, and because this is a tobacco and alcohol related cancer, serious thought should be given to prevention and early tumour detection.
1. La Vecchia C, Lucchini F, Negri E, Levi F. Trends in oral cancer mortality in Europe. Oral Oncol. 2004 Apr;40(4):433-9. [ Links ]
2. Boyle P, Ferlay J. Cancer incidence and mortality in Europe, 2004. Ann Oncol. 2005 Mar;16(3):481-8. Epub 2005 Feb 17. [ Links ]
3. Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol. 2007 Mar;18(3):581-92. Epub 2007 Feb 7. [ Links ]
4. Gillison ML. Current topics in the epidemiology of oral cavity and oropharyngeal cancers. Head Neck. 2007 Aug;29(8):779-92. [ Links ]
5. Nieto A, Ramos MR. Rising trends in oral cancer mortality in Spain, 1975-94. J Oral Pathol Med. 2002 Mar;31(3):147-52. [ Links ]
6. Shiboski CH, Shiboski SC, Silverman S Jr. Trends in oral cancer rates in the United States, 1973-1996. Community Dent Oral Epidemiol. 2000 Aug;28(4):249-56. [ Links ]
7. Silverman S Jr. Demographics and occurrence of oral and pharyngeal cancers. The outcomes, the trends, the challenge. J Am Dent Assoc. 2001 Nov;132 Suppl:7S-11S. [ Links ]
8. Gonzales-Moles MA, Rodriguez-Archilla A, Ruiz-Avila I, Martinez AB, Morales-Garcia P, Gonzalez-Moles S. P16 Expression in squamous carcinomas of the tongue. Onkologie. 2002 Oct;25(5):433-6. [ Links ]
9. Castle JT, Cardinali M, Kratochvil FJ, Abbondanzo SL, Kessler HP, Auclair PL, Yeudall WA. P53 and cyclin D1 staining patterns of malignant and premalignant oral lesions in age-dependent populations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999 Sep;88(3):326-32. [ Links ]
10. Katoh T, Kaneko S, Kohshi K, Munaka M, Kitagawa K, Kunugita N, et al. Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and oral cavity cancer. Int J Cancer. 1999 Nov 26;83(5):606-9. [ Links ]
11. Sato M, Sato T, Izumo T, Amagasa T. Genetic polymorphism of drug-metabolizing enzymes and susceptibility to oral cancer. Carcinogenesis. 1999 Oct;20(10):1927-31. [ Links ]
12. Morita S, Yano M, Tsujinaka T, Akiyama Y, Taniguchi M, Kaneko K, et al. Genetic polymorphisms of drug-metabolizing enzymes and susceptibility to head-and-neck squamous-cell carcinoma. Int J Cancer. 1999 Mar 1;80(5):685-8. [ Links ]
13. Amador AG, Righi PD, Radpour S, Everett ET, Weisberger E, Langer M, et al. Polymorphisms of xenobiotic metabolizing genes in oropharyngeal carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002 Apr;93(4):440-5 [ Links ]
14. Fritz A, Percy C, Andrew Jack, Sobin LH editors. International Classification of Diseases for Oncology (ICD-O), 3rd Ed., Geneva: WHO; 2000. [ Links ]
15. Izarzugaza MI, Esparza H, Aguirre JM. Epidemiological aspects of oral and pharyngeal cancers in the Basque Country. J Oral Pathol Med. 2001 Oct;30(9):521-6. [ Links ]
16. Casiglia J, Woo SB. A comprehensive review of oral cancer. Gen Dent. 2001 Jan-Feb;49(1):72-82. [ Links ]
17. Howell RE, Wright BA, Dewar R. Trends in the incidence of oral cancer in Nova Scotia from 1983 to 1997. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003 Feb;95(2):205-12. [ Links ]
18. Miller CS, Henry RG, Rayens MK. Disparities in risk of and survival from oropharyngeal squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003 May;95(5):570-5. [ Links ]
19. Alvarez Amazaga J, Barbier Herrero L, Pijoan del Barrio JI, Martin Rodriguez JC, Romo Simon L, Genolla Subirats J, et al. Diagnostic efficacy of sentinel node biopsy in oral squamous cell carcinoma. Cohort study and meta-analysis. Med Oral Patol Oral Cir Bucal. 2007 May 1;12(3):E235-43. [ Links ]
20. Hyde NC, Prvulovich E, Newman L, Waddington WA, Visvikis D, Ell P. A new approach to pre-treatment assessment of the N0 neck in oral squamous cell carcinoma: the role of sentinel node biopsy and positron emission tomography. Oral Oncol. 2003 Jun;39(4):350-60. [ Links ]
21. Ohrn KE, Sjoden PO, Wahlin YB, Elf M. Oral health and quality of life among patients with head and neck cancer or haematological malignancies. Support Care Cancer. 2001 Oct;9(7):528-38. [ Links ]
22. Conway DI, Macpherson LM, Gibson J, Binnie VI. Oral cancer: prevention and detection in primary dental healthcare. Prim Dent Care. 2002 Oct;9(4):119-23. [ Links ]
23. Andersson M, Storm HH. Survival of Danish cancer patients 1943-1987. Buccal cavity and pharynx. APMIS Suppl. 1993;33:9-34. [ Links ]
24. Franceschi S, Talamini R, Barra S, Baron AE, Negri E, Bidoli E, et al. Smoking and drinking in relation to cancers of the oral cavity, pharynx, larynx, and esophagus in northern Italy. Cancer Res. 1990 Oct 15;50(20):6502-7. [ Links ]
25. Choi SY, Kahyo H. Effect of cigarette smoking and alcohol consumption in the aetiology of cancer of the oral cavity, pharynx and larynx. Int J Epidemiol. 1991 Dec;20(4):878-85. [ Links ]
26. Voor Gedistilleerde Dranken Productschap. Productschap voor Gedistilleerde Dranken. World Drink Trends 2000. Henley-on-Thames, England: NTC Publications; 2000. [ Links ]
27. Fioretti F, Bosetti C, Tavani A, Franceschi S, La Vecchia C. Risk factors for oral and pharyngeal cancer in never smokers. Oral Oncol. 1999 Jul;35(4):375-8. [ Links ]
28. Figuero Ruiz E, Carretero Pelaez MA, Cerero Lapiedra R, Esparza Gomez G, Moreno Lopez LA. Effects of the consumption of alcohol in the oral cavity: relationship with oral cancer. Med Oral. 2004 Jan-Feb;9(1):14-23. [ Links ]
29. Aydiner A, Karadeniz A, Uygun K, Tas S, Tas F, Disci R, et al. Multiple primary neoplasms at a single institution: differences between synchronous and metachronous neoplasms. Am J Clin Oncol. 2000 Aug;23(4):364-70. [ Links ]
30. Alvarez Marcos CA, Llorente Pendas JL, Franco Gutierrez V, Hermsen MA, Franco Albalad MP, Fernandez Espina H, et al. Second primary tumors in head and neck cancer. Acta Otorrinolaringol Esp. 2006 Dec;57(10):462-6. [ Links ]
Dr. Gonçalo Seguro Dias
Oral Medicine Department
Faculdade de Medicina Dentária
Lisbon University/Universidade de Lisboa