A retrospective multicenter study of oral and maxillofacial lesions in older people

Abstract Few studies on the distribution of oral diseases in older people are available in the literature. This study aimed to investigate the prevalence and demographic characteristics of oral and maxillofacial lesions in geriatric patients (age ≥ 60 years). A retrospective descriptive cross-sectional study was performed. Biopsy records were obtained from archives of three Brazilian oral pathology centers over a 20-year period. Data on sex, age, anatomical site, skin color, and histopathological diagnosis were collected and analyzed. Pearson’s chi-square test was used to evaluate differences in the frequency of the different oral and maxillofacial lesion groups. A total of 7,476 biopsy records of older patients were analyzed. Most cases were diagnosed in patients aged 60 to 69 years (n = 4,487; 60.0%). Females were more affected (n = 4,403; 58.9%) with a female-to-male ratio of 1:0.7 (p < 0.001). The tongue (n = 1,196; 16.4%), lower lip (n = 1,005; 13.8%), and buccal mucosa (n = 997; 13.7%) were the most common anatomical sites. Reactive and inflammatory lesions (n = 3,840; 51.3%) were the most prevalent non-neoplastic pathologies (p < 0.001), followed by cysts (n = 475; 6.4%). Malignant neoplasms were more frequent (n = 1,353; 18.1%) than benign neoplasms (n = 512; 6.8%). Fibrous/fibroepithelial hyperplasia (n = 2,042; 53.2%) (p < 0.001) and squamous cell carcinoma (n = 1,191; 88.03%) (p < 0.001) were the most common oral lesions in older adults. Biopsy data allow the accurate characterization of the prevalence of oral and maxillofacial lesions, supporting the development of public health policies that can enable the prevention, early diagnosis, and appropriate treatment of these lesions. Also, they bring valuable information that helps dentists and geriatricians diagnose these diseases.


Introduction
2][3] Current estimates show that the number of individuals over 60 years will be about 1.2 billion in 2025 and approximately 2 billion in 2050, and 80% of them will be living in developing countries. 4In Brazil, life expectancy has also grown progressively over the years.In 54 years, according to the Brazilian Institute of Geography and Statistics (IBGE), Brazilian life expectancy increased by 26.6 years, from 48 years in 1960 to 74.6 years in 2014. 5This fact demonstrates that the country's development has improved the population's quality of life and has impacted life expectancy in recent decades, following a global trend.
7][8] Studies have shown that the relative frequency of oral potentially malignant disorders (OPMDs) and malignant tumors was 10 times more common in this population than in younger individuals, also increasing with advancing age in older individuals. 1,9Other studies have also shown a statistically higher incidence of reactional and inflammatory lesions, malignant epithelial neoplasms, premalignant lesions, autoimmune diseases, and salivary gland tumors in older adults when compared to younger individuals. 10,11These data support that age has significantly influenced the prevalence and pattern of oral diseases observed in these individuals.This higher prevalence of oral lesions in older adults merits consideration.Public health policies that guarantee an early diagnosis and proper treatment of these diseases should be developed to improve the quality of life of this population. 1,2,6,73][14][15][16][17][18][19] Considering that multicenter studies based on histopathological records can provide more accurate data and are scarce in the literature, 1,6 this study aimed to evaluate oral and maxillofacial lesions diagnosed in older people (aged ≥60 years) in three oral pathology centers in Brazil.To the best of our knowledge, this study is the largest series of oral lesions in Brazilian older adults to date.

Methodology Study design and sampling
In this retrospective multicenter study (1999-2019), histopathological records were retrieved from the archives of three Brazilian oral and maxillofacial pathology centers (Table 1).All older people (≥ 60 years) with lesions in the oral and maxillofacial region who underwent histopathological examination at the participating centers were included in the present study.Data such as age, sex, skin color, anatomical site, and clinical and histopathological diagnosis were obtained from biopsy records and analyzed.Biopsy results that showed no pathological changes were excluded from the present study.
Oral and maxillofacial lesions were grouped into the following categories: a) reactive and inflammatory lesions, b) benign and malignant neoplasms, c) OPMDs, d) cysts, e) immunological diseases, f) infectious diseases, g) non-neoplastic bone lesions, h) pigmented and calcified lesions, and i) normal variations of the oral cavity and tumor-like malformations.Neoplasms were classified according to the current edition of WHO Classification of Tumors. 20Other categories were classified according to previous studies 1,6 and the Manual of Oral and Maxillofacial Pathology, 4th edition. 21Additional immunohistochemical analysis was performed when routine staining (hematoxylin-eosin staining) was insufficient to establish the final diagnosis.The study was approved by the Ethics Committee of the State University of Paraíba (protocol number: 61639722.9.0000.5187).

Data analysis
Descriptive and quantitative data analyses were performed using the Statistical Package for the Social Sciences (SPSS) for Windows 20.0 (SPSS.Inc., Chicago, USA).Continuous variables were expressed as mean, median, and standard deviation.Categorical variables were defined as the absolute number of cases and percentage values.The chi-square test and Fisher's exact test were used to evaluate the association between the different groups of oral lesions and demographic characteristics, adopting a p-value of ≤ 0.05 and a 95% confidence interval.

Results
A total of 34,648 surgical specimens were received at the participating centers; of these, 8,015 (23.1%) were diagnosed in older people (≥ 60 years).However, 539 records were excluded from the analysis because of incomplete data, insufficient material for analysis, and inconclusive/non-specific histopathological findings (Figure 1).The allocation of cases by the centers is presented in Table 1.There was a homogeneous distribution of groups of oral lesions among the participating centers in the present study, and no difference in the prevalence of oral lesions by geographic region (northeast vs. southeast) was observed (Figure 2A-D).
Concerning immunological diseases, oral lichen planus (n = 80; 55.9%), followed by mucous membrane pemphigoid (n = 45; 31.5%) were the most common disorders.Both showed a strong predilection for females, with a female-to-male ratio of 4.3:1 and 3.1:1, respectively (Table 3).Various infectious diseases, pigmented and calcified lesions, nonneoplastic bone lesions, and normal variations of the oral cavity and tumor-like malformations were also found.These lesions exhibited a heterogeneous distribution in older people and are described in detail in Table 3.
The agreement between clinical and histopathologic diagnoses was 55.2% (3,209 of 5,812 cases) for all cases and varied depending on the diagnosis.The highest rate of agreement was related to infectious diseases (82.4%), followed by immunological diseases (67.4%).The lowest rate of agreement was related to cysts (48.7%) and non-neoplastic bone lesions (48.9%) (Table 2).

Discussion
Several studies have reported on the incidence and prevalence of oral lesions in older people, 1,6,7,10,22-27 but many rely solely on clinical diagnosis, [12][13][14][15][16][17][18][19] which can lead to inaccurate findings, as the final diagnosis often requires histopathological analysis, considered the gold standard for diagnosing many diseases. 1In the present study, the overall agreement between clinical and histopathological diagnoses was only 55.2% (3,209 cases) for all cases and varied depending on the diagnosis (48.7-82.4%)(Table 2).It is important to emphasize that the lack of agreement between clinical and histopathological diagnoses can lead to treatment errors and unfavorable patient outcomes.Therefore, healthcare professionals should adopt the practice of sending all biopsied material for histopathological analysis for a more accurate and appropriate evaluation of the patient's condition.
In the present study, the prevalence of oral and maxillofacial lesions in older adults ranged from 18.8% to 26.5% at the participating centers, similar to that of previous studies. 1,25However, other studies have shown higher (31.1%) 26 and lower prevalence rates (9.2%-14.9%). 6,10,27These variations may result from   differences in socioeconomic and cultural patterns between different countries or regions of the same country, which influence the habits and diseases of a population. 1 Another factor that could explain the difference in the prevalence of oral lesions observed between the studies is that some describe a country's national profile or representative regions. 1,6In contrast, others report prevalence rates limited to a single faculty of medicine or dentistry, nursing homes, or institutionalized patients. 7,12,14,18,22he prevalence of oral and maxillofacial lesions has increased in older individuals when compared to younger ones. 1,6With advancing age, the oral lining epithelium becomes thinner, and the underlying connective tissue shows reduced collagen synthesis, fibrotic and degenerative collagen changes, and elastin loss 6 .In addition, reduced immune response, impaired DNA repair capacity, and impaired carcinogenic metabolism make the oral mucosa more permeable to harmful substances and more vulnerable to carcinogenic agents.Therefore, oral lesions tend to develop more frequently and rapidly in aging populations. 6,28However, age alone is not the only factor contributing to the high prevalence of oral lesions in older people.Other factors such as trauma, systemic diseases, poor nutritional status, use of some medications, poor oral hygiene, and use of illfitting dentures may also influence the development of oral lesions. 6n Brazil and other developing countries, individuals aged 60 years or older are considered senior citizens; in developed countries, this classification applies to ≥ 65 years. 1 As shown in Table 2, most patients (n = 4,428; 60.0%) were aged between 60 and 69 years, with a mean age of 69.1 years, similar to the findings of previous studies. 1,7,10,13,15,23The mean age of women and men was also similar, 69.26 ± 7.50 and 68.78 ± 7.44 ( ± SD), respectively.However, a higher average age has been observed in developed countries and reflects better living conditions and health services. 6ost studies assessing the prevalence of oral lesions in older people report a higher frequency in female patients, 1,6,7,12,14,17 as in the present study (59.4%).Some, however, have found a higher prevalence of oral lesions in men. 15,18,19These differences may be influenced by demographic, geographic, social, and cultural factors, 1 such as the ratio of men and women in a population.For instance, in China, where men represent over 50% of the population, a higher prevalence of oral lesions has been reported in men. 19Additionally, disparities in healthcare access and utilization between men and women can affect the identification and diagnosis of these lesions.In Brazil, men, especially those from a lower social background, seem to seek medical and dental care less frequently, which can decrease the likelihood of diagnosing possible oral lesions. 1 Oral lesions occurred on different anatomical sites.The tongue and labial/buccal mucosa were the most affected sites in soft tissues, corresponding to 46.5% of all diagnosed lesions (n = 3,381).On the other hand, intraosseous lesions occurred mainly in the mandible (n = 513; 7.0%).Similar data were reported in previous studies. 1,6The reason why the tongue and labial/buccal mucosa are the most common anatomical locations is that the five most commonly diagnosed lesions occur primarily at these anatomical sites (fibrous/fibroepithelial hyperplasia, SCC, epithelial dysplasia, hyperkeratosis/acanthosis, and lichen planus).
In the present study, the three most common oral lesions in older patients were fibrous/fibroepithelial hyperplasia (n = 2,042; 27.3%), SCC (n = 1,191; 15.9%), and epithelial dysplasia (n = 605; 8.1%), data similar to previous biopsy-based studies. 1,6,22[15][16][17]19,25 This apparent discrepancy among studies is not surprising as many diagnoses can be made based on clinical examination alone and do not require a biopsy.Although our study has higher accuracy because all lesions were histopathologically evaluated, it does not represent the actual prevalence of some lesions routinely diagnosed only by clinical examination.
S evera l st ud ies show t h at react ive a nd inflammatory lesions are the most commonly seen in older individuals. 1,6,22Just over half of all lesions analyzed in the present study were of a reactional and inflammatory nature (51.3%).This high prevalence of reactive and inflammatory lesions may be associated with the greater use of removable dentures by older patients.This may explain why the alveolar mucosa was one of the most affected sites in the present study.Inflammatory fibrous hyperplasias are usually caused by chronic trauma to the oral mucosa in individuals who wear removable dentures. 1,22The quality of removable dentures, anatomical factors, and the length of time of removable denture wearing can lead to the development of these lesions.Therefore, health professionals should provide removable denture wearers with proper instructions. 22,29In addition, seizures, Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions that are more common in older individuals can also influence the development of these lesions. 1,6,18lignant neoplasms were the second most common group of lesions (29.8%) in this population.
In addition, approximately one in five older adults were diagnosed with oral cancer, mainly SCC (83.4%).Oral SCC is the most prevalent oral cancer in older patients. 1,6,7,22It often develops from potentially malignant disorders, which represent the third most common group of lesions in the present study.The clinical presentation, biological behavior, and prognosis of SCC are variable. 1,30Treatment and prognosis depend on tumor size at diagnosis, histological grade, presence of metastases, and the patient's general health status. 1 Despite recent advances in the treatment modality, only about 15% to 40% of patients diagnosed with SCC live longer than five years.These data highlight the urgent need to adopt measures to ensure early detection and diagnosis of these lesions so as to reduce morbidity and mortality and alleviate the main complications of cancer treatment, which significantly reduce the quality of life and survival of these patients. 1,6,30he precise etiology of oral SCC remains unknown, but predisposing factors, such as smoking associated with alcohol use, are well known. 30,31Other habits were also associated with oral SCC, such as chewing betel leaves and inverted smoking habit, commonly observed in Asian countries. 30,31Additional causal factors, such as nutritional deficiencies and DNA oncogenic viruses, have also been suggested. 1,30,31n the present study, 15.2% (n = 1,138) of the older individuals were smokers; of these, 35.0%(n = 398) had SCC, which is consistent with the findings of another Brazilian multicenter study. 1 In the European continent, the fact that the incidence and prevalence of oral cancer are high in France, a country with one of the highest alcohol consumption in the world, has led some researchers to suggest that alcohol consumption may be the determining factor in these cases. 18However, other studies show that alcoholism does not offer a strong association with cases of SCC or potentially malignant disorders. 32,33Nevertheless, the synergistic effects of alcohol and tobacco consumption on the risk of oral SCC are well established. 30,31In the assessed sample, few cases had a history of alcohol consumption (n = 127; 1.7%); however, 73 of these patients (57.5%) had SCC.However, these rates are likely underestimated given the lack of information on smoking and alcohol consumption habits in many clinical records of oral cancer patients.These findings underscore the significance of filling medical records and histopathological examination request forms appropriately, as this is essential for precise diagnosis and evaluation of risk factors for oral cancer development.
Only in studies based on histopathological records can potentially malignant disorders be diagnosed accurately. 6In the present study, epithelial dysplasia was the most common potentially malignant disorder (Table 6).In clinical studies, this type of lesion is often diagnosed as leukoplakia, erythroplakia, or erythroleukoplakia. 6Although studies have shown a statistically significant relationship between male sex and the presence of leukoplakia, only smoking habit and being a former smoker were predictive risk factors associated with potentially malignant disorders. 32he present study observed a low prevalence of infectious diseases at the three oral pathology centers.Many of these diseases reduce the quality of life and should not be overlooked during a routine clinical examination.Candidiasis was the most common infection (39.5%).Cases of oral candidiasis are not common at oral pathology centers because it is a disease often diagnosed clinically, not requiring histopathological analysis. 1,6,22In addition, this type of lesion is usually diagnosed in samples sent to microbiology laboratories. 6Previous biopsy-based studies have also reported a low prevalence of oral infections in older people. 1,6,22nterestingly, paracoccidioidomycosis was the second most common in fection (34.2%).
Paracoccidioidomycosis is a systemic mycosis originally described by Adolfo Lutz in 1908, with the highest incidence recorded in South American countries (Brazil, Argentina, Colombia, and Venezuela).In Brazil, most cases have been reported in the south, southeast, and midwest regions. 34In the present study, all cases of paracoccidioidomycosis were diagnosed at the oral and maxillofacial pathology center located in Rio de Janeiro (southeastern Brazil), an endemic area of this disease.

Conclusion
In summary, oral lesions, most of them reactional and inflammatory, were highly prevalent in older people followed by malignant neoplasms.Due to the high prevalence of malignant tumors and potentially malignant disorders, geriatricians and dentists should perform a thorough periodic oral examination for early detection of these lesions to reduce morbidity and mortality, contributing to a better quality of life.In addition, these professionals should use strategies for helping these patients eliminate risk factors, especially smoking and alcohol consumption, thus acquiring a healthy lifestyle.In addition, the moderate agreement observed between the clinical and histopathological diagnoses reinforces the importance of histopathological analysis of all biopsy material.This practice is essential, considering that clinical evaluations alone may not be sufficient to obtain an accurate diagnosis.

Figure 1 .
Figure 1.Flowchart showing the sample selection from the three oral pathology centers participating in the present study.

Figure 2 .
Figure 2. (A-C) Total number of cases diagnosed at each center and number of lesions diagnosed in older patients between and 2019.(D) Comparison between the number of cases diagnosed in older individuals at each center.

Figure 3 .
Figure 3. Distribution of oral and maxillofacial lesions diagnosed in older people according to age.

Table 1 .
Sources of the reviewed cases.

Table 2 .
Age and sex distribution of oral and maxillofacial lesions diagnosed in older people.
NI: not informed; M: male; F: female; SD: Standard deviation.a Person's chi-square test p < 0.001.* Clinical diagnosis was not informed.

Table 3 .
Frequency of non-neoplastic tumors and tumor-like lesions observed in older people.
Percent in relation to the total number of cases; b Percent within the group; a Person's chi-square test p < 0.001.

Table 4 .
Frequency of malignant neoplasms observed in older people.
a Percent in relation to the total number of cases; b Percent in the group (malignant tumors); a Person's chi-square test p < 0.001.

Table 5 .
Frequency of benign neoplasms observed in older people.
a Percent in relation to the total number of cases; b Percent in the group (benign tumors).

Table 6 .
Frequency of oral potentially malignant disorders observed in older people.Percent in relation to the total number of cases; b Percent in the group (oral potentially malignant disorders).