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Odontoestomatología

versão impressa ISSN 0797-0374versão On-line ISSN 1688-9339

Odontoestomatología vol.22 no.36 Montevideo  2020  Epub 01-Dez-2020

http://dx.doi.org/10.22592/ode2020n36a5 

Research

Profile of oral squamous cell carcinoma at the Anatomic Pathology Laboratory of the School of Dentistry of Universidad de la República, 1982-2015 period

Natalia González Umpiérrez1 
http://orcid.org/0000-0001-9006-1680

Verónica Beovide Cortegoso2 
http://orcid.org/0000-0003-0888-507X

1Cátedra de Anatomía Patológica. Facultad de Odontología, Universidad de la República, Montevideo, Uruguay

2Cátedra de Anatomía Patológica. Facultad de Odontología , Universidad de la República, Montevideo, Uruguay

Abstract

Oral squamous cell carcinoma is the most frequent malignant oral pathology, mainly associated with tobacco, alcohol, and human papillomavirus.

This study aimed to determine the profile of this pathology at the Laboratory of Anatomic Pathology of the School of Dentistry of Universidad de la República between 1982 and 2015. A retrospective, cross-sectional, analytical study was conducted. Statistical analysis performed using the Cox model, Fisher’s exact test, and the Kaplan-Meier method. Of 207 cases, 59.9% were men and 98.5% older than 40. It is usually located on the tongue, with a predominance of histopathologically well and moderately differentiated carcinomas. There was an association between histopathological grade, gender, and age, with an average survival time of 2.36 years and a 43% five-year survival rate. The study allowed us to determine the situation of this pathology in a reference health service and create a database for subsequent studies.

Keywords: head and neck squamous cell carcinoma; epidemiology; survival

Introduction and background

Oral squamous cell carcinoma (OSCC) is the most frequent oral malignancy, accounting for 2%-3% of all malignancies and up to 80%-90% of those of the oral cavity 1-8.

OSCC is a solid malignant tumor originating in the stratified squamous epithelium of the upper aerodigestive tract’s mucosa, characterized by varying degrees of histological differentiation and a high invasive and metastatic potential9. Its etiology is mainly associated with risk factors such as tobacco, alcohol, and human papillomavirus 16 and 18 (HPV) 10-13.

In 2018, the Global Cancer Observatory (GLOBOCAN) reported the following data for Uruguay: 15,101 new cancer cases in a population of 3,469,551 people, with 8,589 deaths and a 5-year prevalence of 35,478 cases, according to sources from the National Cancer Registry (NCR) and the World Health Organization (WHO) 14.

The cancer epidemiological situation of Uruguay-recently published by the NCR- reported the following data on oropharyngeal cancer for 2011-2015 (expressed in adjusted rates per 100,000 inhabitants): a total of 1,529 new cases (1,107 men and 422 women), mainly on the tongue (378 cases) regardless of lingual anatomical site, an incidence of 10.17 and 2.81 for men and women respectively, and a 6.67 mortality rate in men and of 1.21 in women15.

Morphologically, OSCC is a malignant epithelial neoplastic proliferation, consisting of nests, cords, and islets that resemble-to a greater or lesser degree-the original squamous epithelium of the lining mucosa. Currently, OSCC histological grading is based on the WHO’s histological classification and the tumor-invasive front: well differentiated, moderately differentiated, and undifferentiated OSCC 7-8.

OSCC is an aggressive neoplasm with unpredictable biological behavior and an unfavorable prognosis16. The aggressiveness of this malignancy is evident, as despite currently available therapeutic strategies-including surgical removal either exclusively or in combination with radiation therapy and/or chemotherapy -the survival and recurrence rates after five years is poor, where only 50% of the patients diagnosed and treated survive17-19, a situation that has remained unchanged over the last five decades 20-22. Its prognosis is related to factors such as tumor size, presence of metastatic lymph nodes, tumor differentiation, invasion of adjacent structures, location, and treatment 23-24. The TNM staging system, where T stands for primary tumor, N for regional lymph nodes and M for distant metastases, is a universal method of staging the disease in cancer patients, which allows clinicians to make therapeutic decisions. It was updated in 2017 for each topography, in addition to identifying OSCC HPV+ and HPV 25.

This study aimed to determine this pathology profile at the Laboratory of Anatomic Pathology of the School of Dentistry (LAPFO) of Universidad de la República between 1982 and 2015. It also aimed to describe its distribution according to clinical-morphological parameters (age, gender, location, and histopathological grade) and determine its survival rate.

Methodology

1- Ethical considerations

This study was conducted with the approval of the Ethics Committee of the School of Dentistry of Universidad de la República, Montevideo, Uruguay (File 163/16).

2- Study design

A retrospective, cross-sectional and analytical study, with convenience non-probability sampling according to the proposed inclusion and exclusion criteria. The population included all of LAPFO’s biopsy records (11,321) for 1982-2015. The sample included all the cases with histopathological diagnosis of OSCC of the oral mucosa. A sample of 207 OSCC cases (1.8%) was obtained from the total biopsy records for that period (11,321); they met the inclusion and exclusion criteria set out below.

3- Inclusion and exclusion criteria

Inclusion criteria: OSCC with full morphological, clinical data, and recorded variables: age, gender, location, and histopathological grade of the lesion. The OSCC histopathological diagnosis accepted was that recorded in the biopsy report that met the WHO’s histological criteria of malignancy (well differentiated, moderately differentiated, and undifferentiated). Reassessing the histopathological diagnosis was considered when the grade was not detailed according to the established criteria, but it was not necessary in any case. If there were two records (incisional and excisional biopsy) for one patient, it was considered a single case-to avoid duplication-and the histological grading recorded was the one for the excisional biopsy. In contrast, for the date of onset of the disease, the one recorded in the first biopsy with an OSCC diagnosis was considered.

A sample was used to determine the survival rate of OSCC patients; the inclusion criterion was that the record should include the patient’s identity card number, which was necessary to find the patient in the NCR’s database (n=99).

Exclusion criteria: Cases with incomplete data, missing variables (age, gender, location, and histological grading) were excluded.

4- Statistical analysis

Descriptive statistics were used to establish significant relationships between the different clinical-morphological parameters through Fisher’s exact test. Survival curves were created using Kaplan Meier’s methodology. Hypothesis tests were performed at a 5% level, and Survival analysis using software R. The data were analyzed using the Cox proportional-hazards model and based on the potential influence of gender, age, histopathological grade, and clustered location of tumors. The variables were selected with a backward procedure; after adjusting the models, the validity of the proportionality assumption was verified.

Results

The results are shown in Chart 1. An age range between 16 and 99 was recorded, with an average of 63 years ± 12.57, 41.5% (86) between 41 and 60, and 47.8% (99) between 61 and 80. In the sample, 59.9% (124) were male, with a male: female ratio of 1.5:1. Regarding histopathological grade, 44.4% (92) were well differentiated carcinomas, 44.9% (93) moderately differentiated and 10.6% (22) undifferentiated. The most frequent location was the tongue-26.6% (55)-and the alveolar ridge-23.7% (49).

Chart 1: Univariate frequencies of OSCC (n=207) 

Variable correlation showed that the histopathological grade concerning gender and age was significant, showing that men have a higher rate of moderately differentiated OSCC and women, a higher rate of well-differentiated OSCC (p-value=0.031) (Table 1); as for age, those over 81 have a higher rate of undifferentiated OSCC (p-value=0.027) (Table 2).

Table 1: Correlation between histopathological grade and gender 

Fisher’s exact test p-value: 0.031

Table 2: Correlation between histopathological grade and age 

Fisher’s exact test p-value: 0.027

Multivariate analysis of location showed no significant association, possibly due to the multiple locations of OSCC in the oral mucosa. In this study, locations were grouped into eight categories. In women, the most frequent locations were the alveolar ridge-28.9% (24)-and the tongue-26.5% (22)-while in men, OSCC appeared in the tongue in 26.6% of cases (33), and in 20.2% of cases (25), in the alveolar ridge.

Survival analysis was performed with a sample of 99 patients, among whom death occurred in 57 cases; the rest corresponded to censoring. The survival curve (Figure 1) was created, from which it was estimated that the average survival time was 2.36 years with a confidence interval (1.60-8.24), and the five-year survival rate survival was 43%, without considering the stages of the TNM system as they were not included in the records.

Fig. 1: Survival curve, Kaplan-Meier 

According to gender, age, histopathological grade, and location, a statistically significant correlation was found with the histological grade when associating the risk of death. The final model is presented in Chart 2, which shows that patients diagnosed with moderately differentiated OSCC have almost twice the risk of death than patients with well differentiated OSCC (p-value 0.031). When analyzing undifferentiated OSCCs, death occurred in all cases, approximately seven years after follow-up, unlike well differentiated OSCCs, which at the end of the study still had patients that were alive (Fig. 2).

Chart 2: Final Cox proportional-hazards model 

Fig. 2: Survival curves according to histopathological grade 

Discussion

It is essential to study OSCC due to its high morbidity and mortality. It is instrumental to obtain relevant information to compare results with other centers specialized in oral pathology, providing knowledge on survival and clinical-pathological characteristics.

This study made it possible to obtain institutional information for the School of Dentistry of Universidad de la República, establishing the OSCC profile at LAPFO; this allowed us to create a significant database for future studies.

This study had some limitations given the lack of proper anatomical-pathological recording, making TNM staging, and risk factor assessment difficult. Still, it was significant to have a cohort of 99 patients for survival analysis.

In this study, 59.9% of OSCC cases affected men, a figure in line with the literature 19,21,26-27; however, differences were found between the m:f ratio of our study (1.5:1) and that reported by the National Cancer Institute (INCA) in Brazil, which reported a rate higher than 3.7:1 28 and that recently reported by the NCR in Uruguay, which published a 3.6:1 ratio for both men and women 15. The highest frequency among men matches the data reported in GLOBOCAN 2018 14 and by other authors, where OSCC is two or three times more frequent in men in most ethnic groups. In recent years, there has been an increasing trend of OSCC among women due to increased tobacco consumption. This data could explain the 1.5:1 ratio of our study 2,19,29.

A retrospective study published in 2014 by Momares et al., including 217 patients diagnosed with OSCC between 1989 and 2010 and conducted at the Department of Oral Pathology of the School of Dentistry of Universidad Mayor de Chile, showed similar results to those of our study. The results were compared, and it was found that distribution by gender, ratio between genders, age range, and average age were almost identical. The tongue and alveolar ridge were the most frequent locations for both, with some differences in the remaining locations. Regarding histological differentiation, both studies found that well differentiated and moderately differentiated OSCCs were more prevalent than undifferentiated OSCCs 30.

Regarding the age of appearance of OSCC in our study, the mean age was 63±12.57, with an age range of 16 to 99, an OSCC frequency of 41.5% between 41 and 60, increasing to 47.8% in the 61-80 age group. Oliveira et al. in 2015 reported an average age of 60.75±11.26 years in a public hospital in Uruguay, similar to the one observed in this study(19). The literature reports that over 90% of cases are individuals over 40, and more than 50% occur in individuals over 65. In our study, 98.5% occurred in individuals over 40, and 57% in individuals over 60 31-33.

Regarding the onset age of OSCC according to gender, 80% of women and 96% of men are aged between 41 and 80; of those groups, over 50% are in the highest range (61 to 80). In the age range analysis, we found no OSCC records for men in the group under 40, while in the group over 81, women recorded a figure almost three times higher than men.

The most frequent location was the tongue-26.6%-in line with a study conducted at the Laboratory of Anatomic Pathology of INCA of Uruguay in 2017, as reported in the literature in most OSCC studies 34. There is a difference regarding the second most frequent location (alveolar ridge: 23.7%), which most studies report to be the floor of the mouth and/or palate. This may be linked to how OSCC locations are grouped 35-37.

Our histopathological grading results are similar to those obtained by Wei-ping Jie et al.: 90.8% of the cases reported were well differentiated and moderately differentiated OSCC 38. Other studies showed similar data. Sairay et al. showed that 52% of OSCC were moderately differentiated and 42% well differentiated in Pakistan and for the 2015-2016 period 39, while Gul et al. found that 43% of patients in a tertiary hospital in southern Punjab India had well differentiated OSCC, 38%, moderately differentiated OSCC, and 20%, undifferentiated OSCC 40. In 2018, Read et al. studied OSCC in a Brazilian population with low economic development, with n=194 cases; 54.6% were well differentiated, 37.1%, moderately differentiated, and 5.2%, undifferentiated carcinomas. Therefore, this study has a similar profile to that of our study 41.

When connecting variables, we found a statistical significance in OSCC histopathological grade in relation to gender and age. Men had a higher rate of moderately differentiated carcinomas, and women a higher rate of well differentiated OSCC. This indicates that the rate of undifferentiated carcinomas increases with age. This matches the results of a study published in 2010 on the clinical-histopathological characteristics of OSCC at San Vicente de Paúl University Hospital, Colombia 42.

The five-year survival rate of OSCC patients was 43%, similar to that reported by Momares et al. in Chile, which was 46%, while their average survival time was 6.9 years, higher than that found in our study, which was 2.36 years 30. Other authors report a survival rate ranging from 30% to 50% for OSCC33-43.

Oliveira et al. show an even lower overall survival rate, with a 24% five-year survival 19. In 2014, Bonfante et al. conducted a national study of Brazil’s Unified Health System for 2000-2006. They reported a five-year survival rate of 4.6-years for mouth cancer, and a five-year overall survival rate of 2.6-years, similar to our findings (2.36 years) 44. Another study with 274 cases from the University of Buenos Aires (Argentina) evaluated overall survival for oral cancer and reported a five-year survival rate of 39% 45.

Conclusions

In general, OSCC studies in Uruguay are scarce, mainly regarding patient prognosis and survival. Retrospective studies such as this one have significant limitations given the lack of complete records, missing-in most cases-relevant clinical data to establish a TNM staging system, and mainly due to the lack of patient follow-up. However, these descriptive studies are a source of hypotheses for further analytical studies.

Considering the high mortality and morbidity of OSCC, health professionals should consider the importance of early detection of these injuries and education on known risk factors, such as tobacco, alcohol, and HPV infection, bearing in mind that late diagnosis is one of the main factors concerning poor prognosis.

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Authorship contribution 1) Conception and design of study 2) Acquisition of data 3) Data analysis 4) Discussion of results 5) Drafting of the manuscript 6) Approval of the final version of the manuscript NGU has contributed in 1, 2, 3, 4, 5, and 6. VBC has contributed in 1, 4, 5, and 6.

Editor’s opinion: This article has been accepted by the Odontoestomatología’s editor Dra. Vanessa Pereira-Prado

Received: October 29, 2019; Accepted: September 08, 2020

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