ABSTRACT

Objective

To evaluate the epidemiological profile and survival rate of oral and oropharyngeal cancer patients seen at a university hospital.

Methods

A cross-sectional study was carried out by means of the pathological reports of patients with oral and oropharyngeal cancer, seen at a university hospital of the Southern Region, between January 2004 and December 2014. Information was collected on patients and tumors. The mortality rate was gathered from the patient death registry in the Mortality Information System. Data were analyzed using the Kaplan-Meier survival curve and the log-rank test to compare variables.

Results

The 5- and 10-year survival rates were 42% and 38%, respectively. The anatomical location had a significant association with survival rate (p=0.001), with the rates were better in the lips (p=0.04), and worse in the oropharynx (p=0.03). There were no statistically significant differences between survival rates according to age, sex, ethnicity, schooling level and histologic grade.

Conclusion

The survival rates of oral and oropharyngeal cancer were and associated with the anatomical site of the tumor.

Keywords
Mouth neoplasms/epidemiology; Survival rate; Oropharyngeal neoplasms/epidemiology; Prognosis

RESUMO

Objetivo

Avaliar o perfil epidemiológico e a taxa de sobrevida do câncer de boca e orofaringe de pacientes atendidos em um hospital universitário.

Métodos

Foi realizado um estudo transversal por meio dos laudos anatomopatológicos dos pacientes com câncer de boca e orofaringe atendidos em um hospital universitário, na Região Sul, entre janeiro de 2004 a dezembro de 2014. A partir destes laudos, foram coletadas informações sobre o paciente e o tumor. A taxa de mortalidade foi obtida do registro de óbitos dos pacientes no Sistema de Informações sobre Mortalidade. Os dados foram analisados utilizando a curva de sobrevida pelo método de Kaplan-Meier e o teste de log-rank para a comparação das variáveis.

Resultados

As taxas de sobrevida em 5 e 10 anos foram 42% e 38%, respectivamente. A localização anatômica apresentou associação significativa com a taxa de sobrevida (p=0,001), sendo que, em lábio, os índices foram melhores (p=0,04) e, em orofaringe, piores (p=0,03). Não houve diferenças estatisticamente significantes entre as taxas de sobrevida de acordo com idade, sexo, etnia, nível educacional e grau histológico.

Conclusão

As taxas de sobrevida do câncer de boca e orofaringe foram baixas e associadas à localização anatômica do tumor.

Descritores
Neoplasias bucais/epidemiologia; Taxa de sobrevida; Neoplasias orofaríngeas/epidemiologia; Prognóstico

INTRODUCTION

Head and neck cancers are a serious public health problem due to their high incidence, prevalence, and mortality.⁽¹1. Boing AF, Antunes JL. [Socioeconomic conditions and head and neck cancer: a systematic literature review]. Cien Saude Colet. 2011;16(2):615-22. Review. Portuguese.⁾ Tumors of the mouth and oropharynx are some of the most frequent in this group,⁽²2. Chin D, Boyle GM, Porceddu S, Theile DR, Parsons PG, Coman WB. Head and Neck Cancer: past, present and future. Exp Rev Anticancer Ther. 2006;6(7): 1111-8. Review.⁾ and accounted for more than 219 thousand deaths worldwide, in 2012.⁽³3. World Healt Organizatio (WHO). World Cancer Report 2014. Edited by Stewart BW, Wild CW. Lyon: International Agency for Research on Cancer; 2015. p. 423.⁾ Approximately 90% of them are squamous cell carcinoma (SCC).⁽⁴4. Dewan AK, Dabas SK, Pradhan P, Mehta S, Dewan A, Sinha R. Squamous cell carcinoma of the superior gingivobuccal sulcus: an 11-year institutional experience of 203 cases. Jpn J Clin Oncol. 2014;44(9):807-11.⁾

The majority of patients diagnosed with oral and oropharyngeal cancer have a history of smoking and alcohol consumption, which are important etiologic factors.⁽⁵5. Harris SL, Kimple RJ, Hayes DN, Couch ME, Rosenman JG. Never-smokers, never-drinkers: unique clinical subgroup of young patients with head and neck squamous cell cancers. Head Neck. 2010;32(4):499-503.⁾ Further, human papillomavirus (HPV) infection has been associated with development of oropharyngeal cancer.⁽⁶6. Elrefaey S, Massaro MA, Chiocca S, Chiesa F, Ansarin M. HPV in oropharyngeal cancer: the basics to know in clinical practice. Acta Otorhinolaryngol Ital. 2014;34(5):299-309. Review.⁾

Five-year survival rates of oral and oropharyngeal cancer are approximately 50%. The majority of patients live for a short time after diagnosis,⁽⁷7. Epstein JB, Gorsky M, Cabay JR, Day T, Golsalves W. Screening for and diagnosis of oral premalignant lesions and oropharyngeal squamous cell carcinoma. role of primary care physicians. Can Fam Physician. 2008;54(6): 870-5. Review.⁾ because most tumors are identified late, compromising treatment, prognosis, and survival of patients.⁽⁸8. Warnakulasuriya S. Living with oral cancer: epidemiology with particular reference to prevalence and life-style changes that influence survival. Oral Oncol. 2010;46(6):407-10. Review.^,99. Martinez C, Hernandez M, Martinez B, Adorno D. Frecuencia de displasia epitelial y carcinoma escamoso en mucosa oral y orofaríngea en Chile, entre los años 1990 y 2009. Rev Med Chile. 2016;144(2):169-74.⁾ Therefore, it is necessary to disseminate information and statistical data regarding oral and oropharyngeal cancer to encourage professionals towards carrying out actions for early detection, contributing to a better understanding of the disease and of more feasible therapeutic proposals, and consequently increasing survival rates.⁽¹⁰10. Onofre MA, Sposto MR, Simões ME, Scaf G, Ferreira LA, Turatti E. Prevalência de câncer bucal no serviço de medicina bucal da Faculdade de Odontologia de Araraquara/UNESP: 1989-1995. Rev Gaucha Odontol. 1997;45(2):101-4.⁾

OBJECTIVE

To analyze the epidemiological profile and survival of patients with oral and oropharyngeal cancer at a university hospital.

METHODS

This was a cross-sectional study by analysis of pathological reports of patients diagnosed with oral and oropharyngeal cancer at a university hospital in the Southern Region of the country, between January 2004 and December 2014. This is a teaching hospital integrated to a federal university in the city of Santa Maria (RS), which is considered a reference for the central region of the state.

The information collected was stored in the Teaching Information System, a digital system of the Department of Pathology of the university. In these reports, we selected the patients diagnosed with SCC of the mouth and oropharynx. The following variables were collected: municipality, sex, age, ethnicity, schooling level, histology grade, and anatomical site. Incomplete reports and patient data of those who had recurring cancer of the mouth and oropharynx were excluded.

Ethnicity was divided into white and non-white. Schooling level was divided into 8 years or less of education, and more than 8 years, and age was divided into decades (≤49, 50-59, 60-69, and ≥70 years).

The histologic grade was divided into three categories: well-differentiated, moderately differentiated, and poorly differentiated. Regarding anatomical site of tumor, the cases were considered according to codes of the International Classification of Diseases (ICD), tenth edition, in which C00 and C06 correspond to cancer of the mouth, and C10, to cancer of the oropharynx.

Data on mortality were acquired from the Mortality Information System (SIM) (NIS/DAT/CEVS/SES/RS - http://www2.datasus.gov.br/DATASUS/index.php?area=060701). For the survival analysis calculation, Kaplan-Meier method was used with information from the date of histopathological diagnosis until the date of death. After the descriptive analysis, the log-rank test was used to assess the factors related to survival. This analysis was done using Cox's regression model and p<0.05 was considered statistically significant. Data were analyzed using the Stata 12.0 software (Stata Corporation; College Station, Texas, United States).

The study was approved by the Ethics in Research with Human Beings Committee of the Universidade Federal de Santa Maria, opinion no. 924.661, CAAE protocol: 39197314.5.0000.5346.

RESULTS

Of 254 patients diagnosed with oral and oropharyngeal cancer between 2004 and 2014, only 155 were included in the study since their data were complete in the reports analyzed. Among 155 patients, 39% were from the municipality of Santa Maria, and the other 61% were residents of nearby cities. As to sex, 87% were male and 13%, female. The most affected age group was the fifth decade of life, with a minimum age of 25 and a maximum of 86 years. As to race/ethnicity, most were white, corresponding to 95% of cases, and non-white to 5%. As to schooling level, 90% of individuals analyzed had less than 8 years of formal education.

The tongue was the most prevalent site (28%), followed by other parts of the mouth (23%), lips (20%), oropharynx (15%), and floor of the mouth (14%). As to distribution of cases according to histologic grade of the lesion, 49% presented with moderately differentiated SCC, 33% well-differentiated, and 12% poorly differentiated (Table 1).

As to death rates, 49% died due to oral and oropharyngeal cancer over the 10-year period. The mean survival time was 4 years (95% confidence interval − 95%CI 4.44-5.90). In 5 and 10 years, the survival rate was 42% and 38%, respectively. Overall survival is represented in figure 1. There were no statistically significant differences relative to survival according to age, sex, ethnicity, schooling, and histologic grade (Table 2). In reference to survival related to site, there was statistical difference (p=0.001), in which patients with cancer of the lip had a better survival rate (p=0.04), and patients with oropharyngeal cancer, the worst survival (p=0.03) (Figure 2).

DISCUSSION

Cancer of the mouth and oropharynx is characterized by high prevalence, mortality, and low survival rates.⁽¹¹11. Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009;45(4-5):309-16. Review.⁾ In this study, we evaluated the epidemiological profile and the survival rate of patients with oral and oropharyngeal cancer, diagnosed at a hospital in the countryside of the State of Rio Grande do Sul. Results showed a low survival rate in these individuals. Additionally, the anatomical tumor site showed a significant association with survival, since individuals with cancer of the lip presented with better percentages, while those whose disease was in the oropharynx had the worst rates.

In this study, the majority of patients who sought treatment at the hospital were from neighboring cities, highlighting the importance of these services and of reference hospitals to treat the population. In general, the epidemiological profile of these patients was similar to other studies in the literature.⁽¹²12. Bonfante GM, Machado CJ, Souza PE, Andrade EI, Acurcio FA, Cherchiglia ML. [Specific 5-year oral cancer survival and associated factors in cancer outpatients in the Brazilian Unified National Health System]. Cad Saude Publica. 2014;30(5):983-97. Portuguese.^,1313. Ligier K, Belot A, Launoy G, Velten M, Bossard N, Iwaz J, Righini CA, Delafosse P, Guizard AV; network Francim. Descriptive epidemiology of upper aerodigestive tract cancers in France: incidence over 1980-2005 and projection to 2010. Oral Oncol. 2011;47(4):302-7.⁾ Men were more often diagnosed with oral cancer than women, probably for being more exposed to risk factors. However, the number of women affected by this neoplasm has been growing over the years, since they are now exposing themselves more to tobacco and alcohol.⁽¹⁴14. Gervàsio OL, Dutra RA, Tartaglia SM, Vasconcelos WA, Barbosa AA, Aguiar MC. Oral squamous cell carcinoma: A retrospective study of 740 cases in a Brazilian Population. Braz Dent J. 2001;12(1):57-61.⁾ Also identified in this research was a higher frequency of cancer in white individuals and in the fifth decade of life, as well as the higher prevalence at the site of the tongue and moderate histologic grade, which are characteristics also described in other studies.⁽¹⁵15. Elwood JM, Youlden DR, Chelimo C, Ioannides S, Baade JD. Comparison of oropharyngeal and oral cavity squamous cell cancer incidence and trends in New Zealand and Queensland, Australia. Cancer Epidemiology. 2014;38(1): 16-21.^–1717. Dedivitis RA, França CM, Mafra AC, Guimarães FT, Guimarães AV. [Clinic and epidemiologic characteristics in the with squamous cell carcinoma of the mouth and oropharynx]. Rev Bras Otorrinolaringol. 2004;70(1):35-40. Portuguese.⁾

As to survival, in this study, we noted a low rate, corresponding 5 and 10 years, respectively, to 42% and 38%. These results are better than those found the Southern region of Thailand, where the 5 and 10 year survival were 24.1% and 25.95%, respectively. The authors attributed these findings to the advanced stage of the disease when patients were diagnosed, and to the type of treatment provided.⁽¹⁸18. Pruegsanusak K, Peeravut S, Leelamanit V, Sinkijcharoenchai W, Jongsatitpaiboon J, Phungrassami T, et al. Survival and prognostic factors of different sites of head and neck cancer: an analysis from Thailand. Asian Pac J Cancer Prev. 2012;13(3):885-90.⁾ Nevertheless, a study carried out in the Netherlands, from 1989 to 2011, demonstrated patients diagnosed with oral and oropharyngeal SCC responded better to treatments, increasing the survival rate to 67% and 48%, respectively in oral cavity and oropharyngeal cancers.⁽¹⁹19. Braakhuis BJ, Leemans CR, Visser O. Incidence and survival trends of head and neck squamous cell carcinoma in the Netherlands between 1989 and 2011. Oral Oncol. 2014;50(7):670-5.⁾ Therefore, we note that survival rates are better in more developed countries as compared to developing ones.⁽⁸8. Warnakulasuriya S. Living with oral cancer: epidemiology with particular reference to prevalence and life-style changes that influence survival. Oral Oncol. 2010;46(6):407-10. Review.⁾

The present study demonstrated the variables age, sex, ethnicity and schooling did not show a significant association with survival rates of oral and oropharyngeal cancer, just as in the study by Schneider et al.⁽²⁰20. Schneider IJ, Flores ME, Nickel DA, Martins LG, Traebert J. Survival rates of patients with cancer of the lip, mouth and pharynx: a cohort study of 10 years. Rev Bras Epidemiol. 2014;17(3):680-91.⁾ However, in an investigation conducted in São Paulo from 1999 to 2002, the authors observed that individuals with more advanced age presented with the worst survival rates, and this, as per the authors, could be related to the occurrence of debilitating diseases and other complications associated with aging.⁽²¹21. Oliveira LR, Ribeiro-Silva A, Costa JP, Simões AL, Matteo MA, Zucoloto S. Prognostic factors and survival analysis in a sample of oral squamous cell carcinoma patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008; 106(5):685-95.⁾ A recent study aimed to evaluate the influence of ethnicity on survival of oropharyngeal cancer patients, and the variable showed a significant association, unlike the present study. The authors noted that black patients had the worst survival rates, which were probably attributed to the worst socioeconomic conditions of these individuals, hindering access to treatment.⁽²²22. Megwalu UC, Ma Y. Racial disparities in oropharyngeal cancer survival. Oral Oncol. 2017;65:33-7.⁾

It was also noted that the histologic grade showed no significant relation to survival of patients with oral and oropharyngeal cancer. Nevertheless, Kademani et al.,⁽²³23. Kademani D, Bell RB, Bagheri S, Holmgren E, Dierks E, Potter B, et al. Prognostic factors in intraoral squamous cell carcinoma: the influence of histologic grade. J Oral Maxillofac Surg. 2005;63(11):1599-605.⁾ demonstrated the histologic grade was a predictive factor for oral cancer, and the tumors presenting with a poorly differentiated grade had the worst survival rates. According to the authors, this finding was justified by the fact that neoplasms with this histologic characteristic presented with a greater prevalence of cervical metastasis. Here, the histologic grade may not have shown an association with the survival rates due to limitations of the study design − since the retrospective studies evaluate the patients’ medical records, which contained incomplete data, thus diminishing the sample in the present investigation.

As to the anatomical site of the tumor, patients with cancer in the lip region had better survival rates, and those located in the oropharynx had the worst rates. Sites with more blood and lymph vessels, besides difficult to assess sites that hinder the diagnosis and treatment, can influence the progression and prognosis of the tumor.⁽²⁴24. Massano J, Regateiro FS, Januàrio G, Ferreira A. Oral squamous cell carcinoma: Review of prognostic and predictive factors. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;102(1):67-76. Review.⁾ In this regard, the lip region is more accessible, facilitating early detection and diagnosis, resulting, consequently, in better survival rates.⁽²⁵25. Epstein JB, Gorsky M, Cabay RJ, Day T, Gonsalves T. Screening for and diagnosis of oral premalignant lesions and oropharyngeal squamous cell carcinoma. Can Fam Physician. 2008;54(6):870-875.⁾

Oropharyngeal cancer is strongly associated with cervical metastases, with incidence of 50 to 70%,⁽²⁶26. Becker M. Oral cavity, oropharynx and hypopharynx. Semin Roentgenol. 2000; 35(1):21-30. Review.⁾ due to its greater tumor dissemination, besides being located in regions difficult to visualize and diagnose, contributing negatively to patient survival,⁽²⁷27. Vogel DW, Zbearen P, Thoeny CH. Cancer of the oral cavity and oropharynx. Cancer Imaging. 2010;10(1):62-72.⁾ as was observed in this study. Additionally, HPV-positive patients diagnosed with oropharyngeal cancer are related to a better prognosis than those who are HPV-negative. This fact can be related to the low percentage of mutation present in these tumors, predisposing towards better responses to treatment and high survival rates,⁽²⁸28. Oguejiofor KK, Hall JS, Mani N, Douglas C, Slevin NJ, Homer J, et al. The Prognostic Significance of the Biomarker p16 in Oropharyngeal Squamous Cell Carcinoma. Clin Oncol (R Coll Radiol). 2013;25(11):630-8.⁾ differently from that found in this study. Nevertheless, in the present study, it was not possible to evaluate this association due to the absence of data in the system on presence of HPV. Further studies should be conducted to evaluate the influence of HPV in oropharyngeal cancers.

CONCLUSION

The survival rate of patients with oral and oropharyngeal cancer was shown to be low in this study. The anatomical site influenced patient survival, in which tumors located in the oropharynx presented with worse survival rates, while those located on the lip had the best rates.

REFERENCES

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