|Year : 2014 | Volume
| Issue : 4 | Page : 908-914
Oral squamous cell carcinoma in a South African sample: Race/ethnicity, age, gender, and degree of histopathological differentiation
RA Khammissa1, S Meer2, J Lemmer1, L Feller1
1 Department of Periodontology and Oral Medicine, University of Limpopo, Medunsa Campus, Limpopo Province, South Africa
2 Department of Oral Pathology, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa
|Date of Web Publication||9-Jan-2015|
Department of Periodontology and Oral Medicine, Box D26 School of Dentistry, Medunsa-0204
Source of Support: None, Conflict of Interest: None
Objectives: The purpose of this retrospective study was to investigate differences between black and white persons with oral squamous cell carcinoma (OSCC) with regard to age, gender, oral site affected, and histopathological degree of differentiation; and to compare these clinicopathological parameters between persons younger and older than 40 years in a South African population sample from the greater Johannesburg area.
Material and Methods: The histopathological reports of 510 cases of OSCC during the period 1995-2002 were retrospectively evaluated, and the data regarding age, gender, ethnicity/race, oral site affected, and degree of histopathological differentiation were recorded and statistically analyzed for differences between black and white persons, and between persons younger and older than 40 years of age.
Results: Statistically significantly, black persons were diagnosed with OSCC at a younger mean age (57 years) than white persons (61 years) (P = 0.0086). The difference between male: female (M: F) ratio in black (3.74:1) and white persons (1.96:1) was statistically significant (P = 0.0041). White persons had a significantly higher proportion of SCC of the lower lip than black persons (P < 0.0001).
Conclusion: OSCC was diagnosed at a younger age in black than in white persons; the proportion of black males in the black population group was greater than that of white males in the white population group; and the proportion of SCC of the lips was higher in younger than in older persons.
结果：黑的人被诊断为口腔鳞状细胞癌的平均年龄较年轻（57岁），相比白种人（61岁）（P = 0.0086），有统计学意义。男性：女性（男：女）的差值比，黑人为（3.74:1），白人（1.96:1），有统计学意义（P = 0.0041）。白人下唇发生鳞癌的比例比黑人更明显（P＜0.0001）。
Keywords: Age, degree of histopathological features, gender, race, squamous cell carcinoma, South Africa
|How to cite this article:|
Khammissa R A, Meer S, Lemmer J, Feller L. Oral squamous cell carcinoma in a South African sample: Race/ethnicity, age, gender, and degree of histopathological differentiation. J Can Res Ther 2014;10:908-14
|How to cite this URL:|
Khammissa R A, Meer S, Lemmer J, Feller L. Oral squamous cell carcinoma in a South African sample: Race/ethnicity, age, gender, and degree of histopathological differentiation. J Can Res Ther [serial online] 2014 [cited 2020 Mar 31];10:908-14. Available from: http://www.cancerjournal.net/text.asp?2014/10/4/908/138100
| > Introduction|| |
Oral squamous cell carcinoma (OSCC) is the most common oral malignant neoplasm representing more than 90% of all oral cancers. It may arise either de novo or from preexisting potentially malignant lesions, within a field of precancerized epithelium.  OSCC may affect any oral site, but most frequently the tongue and the floor of the mouth. The main risk factors associated with OSCC include tobacco/betel/areca nut use, alcohol consumption, infection with high-risk human papillomavirus (HPV) genotypes, and a diet low in fruits and vegetables. ,, The incidence, prevalence, and other epidemiological parameters of OSCC vary greatly between different populations living in different parts of the world, and between different ethnic groups within the same population group.  These differences may be attributed to environmental-specific factors, to exposure to ethnic-specific high-risk habits, and to genetic factors. 
OSCC is predominantly a disease of elderly people, but in recent years there has been an increase in the incidence of the disease in people below the age of 45 years , and even below the age of 40 years. , The risk of developing multiple OSCCs is higher in young persons than in older persons, , but it appears that the clinical and histopathological features and the prognosis of OSCC in younger and in older groups is similar. ,,
Information about the clinical, epidemiological, and histopathological features of OSCC in different ethnic groups in South Africa is limited, and was obtained from surveys conducted in the pre-1994 political era when affected black persons for various reasons may not have been fully represented in the surveys, thus skewing the data. ,,
The aim of this study is to identify the differences between some epidemiological, clinical, and histopathological features of OSCC in black and white, and in younger (≤40 years) and older (>40 years) persons in the greater Johannesburg area of South Africa.
| > Materials and Methods|| |
The records of all cases diagnosed with OSCC over the 8-year period 1995-2002 were reviewed. We limited our study to the period 1995-2002 because after 2002, for reasons of political correctness, ethnic/racial data were not recorded in the histopathological records. Data on preexisting potentially malignant oral conditions, alcohol consumption, tobacco/betel/areca nut use, and other risk factors were not systematically recorded in the pathology submission forms, and so were omitted from the study.
Age, gender, oral site affected, and the histopathological degree of differentiation according to the World Health Organization (WHO) classification system were tabulated  and correlated with race/ethnicity. We decided on 40 years as the cutoff age between younger and older persons, in accordance with previous reports in the literature. ,,,
In some persons more than one oral site was affected by SCC, and some of the OSCCs were 'new second cancers'. In this article, the term 'new second cancer' refers to a cancer that had arisen in the mouth sometime after a primary OSCC had been diagnosed and treated, and thus, may have developed either independently or as a result of resurgence of the primary OSCC.
The Chi-square test was used to determine the association between two categorical variables. Fisher's exact test was used for two by two (2 × 2) tables. The t-test was used to determine differences in a continuous variable with regard to a categorical variable. Differences in proportions were assessed by the z-test. The influence of gender and ethnicity on patient age was tested by a two-way analysis of variance (ANOVA) with interaction. The 0.05 significance level was applied throughout the investigation.
| > Results|| |
During the study period 1995-2002, regardless of the nature of the lesion, of all biopsy specimens examined at this particular laboratory in South Africa; 65% were of black persons, 30% were of white persons, 3% were of coloreds (mixed race), and 2% were of Asians. Bearing in mind the possibility of the referral bias to different laboratories for regional and administrative reasons, the proportional distribution of biopsy specimens received by this particular laboratory, was taken as probably reflecting the general ethnic distribution of the population living in the greater Johannesburg area. Broadly reflecting this general ethnic distribution, of the 510 specimens of OSCC that comprised our study population, 69% (351) were from blacks, 28% (145) were from whites, and there were equal numbers of coloreds and Asians (n = 7; 1.5%).
Altogether, the data of 813 persons with OSCC was recorded in the laboratory during the period 1995-2002. In those persons whose biopsies were taken either during radical surgery, from metastatic SCCs or from salivary gland SCCs; or for those for whom some data with regard to age, gender, racial/ethnic background, oral site affected, or histopathological grading were missing, were excluded, totaling 303 exclusions. This left a study population of 510 persons who had 554 sites affected by OSCC. Four hundred and sixty six persons (91%) had one affected site and 44 persons (9%) had two affected sites. No persons had more than two affected sites. In 27 persons (5%), the OSCC was a new second cancer.
The demographic data of the study population is shown in [Table 1]. There was a wide age distribution. There were significantly more males than females with OSCC (male: female (M: F) =2.92:1) (P < 0.001) [Table 1]. The M: F ratio in black persons (3.74:1) and white persons (1.96:1) were statistically significantly different (P = 0.0041). Excluding the colored and Asian groups that were numerically very small, within the combined white and black study population (n = 496), the proportion of black males with OSCC (79%) was higher than the proportion of white males (66%). Statistically significantly, black persons were diagnosed with OSCC at a younger mean age than white persons (P = 0.0086) [Table 1].
|Table 1: Race/ethnicity in relation to age, gender, site affected, and histopathological type for the entire study population|
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Overall, the sites in the mouth most commonly affected by SCC were the tongue and the floor of the mouth [Table 1]. Blacks were significantly more frequently affected by SCC of the tongue than were whites (P = 0.032); but SCC of the lower lip was significantly more frequent in whites than in blacks (P < 0.0001) [Table 1].
Differences in histopathological grading of OSCC by race/ethnicity are shown in [Table 1]. The proportion of well-differentiated OSCCs was higher in whites than in blacks while the proportion of poorly-differentiated OSCCs was higher in blacks than in whites (P < 0.0001). The proportion of moderately-differentiated OSCCs was approximately equal in blacks and whites.
Of the 510 persons with OSCC, in 44 (9%) multiple sites were affected, 29 (66%) were black, 12 were white (27%), two were Asians (5%) and one was colored (2%). At the time of diagnosis, the mean age of these 44 persons was 59 years. There were no statistically significant difference between the mean age (P = 0.63), gender (P = 0.47), and race/ethnicity (P = 0.21) of the 466 persons with a single oral site affected and of the 44 persons with multiple sites affected; and within the group of 44 persons with multiple affected sites, there were no statistically significant differences between black and white persons in relation to age (P = 0.46), gender (P = 0.40), or degree of histopathological differentiation (P = 0.093).
Twenty-seven (5%) of the persons included in this study had a new second cancer [Table 2]; 22 (81%) had the new second OSCC at the initial site of the primary OSCC, and five (19%) had second OSCCs at different oral sites. There were no statistically significant differences between the mean age (P = 0.69), the gender (P = 1.00), or the race/ethnicity (P = 0.13) of the persons with only primary OSCC and the persons with new second OSCCs. Within the group of persons with new second OSCCs, the males were diagnosed at a statistically significantly younger mean age than the females (P = 0.025). The proportion of black males (93%) with new second OSCCs was significantly higher than the proportion of white males (58%) with new second OSCCs (P = 0.037) [Table 2]. Seventy percent of all sites affected by new second OSCCs were the tongue and floor of the mouth. The time periods from the diagnosis of the primary OSCCs to the diagnosis of the second new OSCCs were unknown. The three histopathological grades of differentiation of OSCCs were not significantly different among black and white persons (P = 0.62).
|Table 2: Race/ethnicity in relation to age and gender for the patients affected by new second OSCC|
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The whole subgroup of the 496 black and white persons in our study population was further categorized into two subgroups according to age [Table 3]. The older subgroup (>40 years) comprised 464 persons (91%) with 501 sites affected; and the younger subgroup (≤40 years) comprised 32 persons (9%) with 36 sites affected by OSCC. New second cancers occurred with similar frequencies in the older and younger subgroups (5 and 6%, respectively).
SCC of the upper and lower lips taken together, occurred significantly more frequently in the younger (28%) than in the older subgroup (6%) (P < 0.0001); and OSCC of the of floor of the mouth occurred significantly less frequently in the younger (6%) than in the older subgroup (29%) (P = 0.0022). The different histopathological grade of OSCCs with regard to race/ethnicity for both subgroups is shown in [Table 3]. The small number of cases in the subgroup of younger persons limited the statistical validity of any differences in clinical and histopathological parameters between blacks and whites.
|Table 3: Race/ethnicity in relation to age, gender, site affected, and histopathological type for patients ≤40 and >40 years|
Click here to view
| > Discussion|| |
The results of our study confirm previous reports that OSCC is generally a disease of middle-aged or elderly people, is more frequently seen in males than in females and may affect any oral site. ,,,,,,, However, despite these general trends; the age, gender, and oral site affected vary between inhabitants of different geographic locations and between different racial/ethnic groups. ,, These variations are most probably owing to differences in genetic predisposition of different racial groups to cancer, to ethnic-specific high-risk habits and cultural practices, to limited access to healthcare services of some socioeconomic groups, and to different environmental factors. ,
In this study, the mean age of our study population at the time of diagnosis of OSCC was 58 years, similar to the mean age of 62 years reported in the USA;  and the M: F ratio was 2.9:1, similar to the M: F ratio reported from the UK of 2.1:1.  It has been suggested that OSCC affects males more frequently than females because the former indulge in high-risk habits more than the latter. , However, in some parts of the world the incidence of OSCC in females is increasing, perhaps because of their increasing indulgence in high-risk habits.  Women who have had hysterectomies and who therefore become menopausal at a younger than average age tends more frequently to develop OSCC. This suggests that estrogen deficiency may play a role in the pathogenesis of OSCC in some women. 
The results of this study support previous findings from South Africa , and from the USA  that there are significant differences between black and white persons with OSCC with regard to clinical, epidemiological, and histopathological features of the disease; that black persons are diagnosed with OSCC at a younger age than white persons;  and that OSCC affects black males, white males, white females, and black females in a declining order of frequency [Table 1].
In black persons, the tongue is the most frequently affected oral site (40%) followed by the floor of the mouth (28%), while in white persons the tendency is the reverse (floor of mouth 32%; tongue 30%). This is broadly in accordance with reports from the USA which show that in black and in white persons with OSCC as a group, the tongue and then the floor of the mouth are the most commonly affected sites.  In this study, histopathologically, 80% of the OSCCs were moderately differentiated and only 6% were well-differentiated. This is in line with findings reported in 2012, that at the time of diagnosis, 70% of oral and oropharyngeal SCCs are moderately differentiated and about 15% are well-differentiated. 
In our study, the frequency of moderately-differentiated OSCCs was more or less the same in blacks and whites, but the frequency of well-differentiated OSCCs was significantly higher in white than black persons, while the reverse was true for poorly-differentiated OSCCs. This may account in part for the observation that in general the clinical behavior of OSCC in black persons is more aggressive than in white persons.  The reasons why black persons tend to develop OSCC at a younger age than white persons is obscure.
It has always been received wisdom that poorly-differentiated OSCC is more aggressive and has a poorer prognosis than well-differentiated OSCC. However, focused studies have shown that degree of differentiation does not correlate well with prognosis. ,,,
Usually, most of the cells at the invasive front of the cancer are more poorly differentiated, while the cells closer to the surface of the cancerous mass are more mature. , As the histopathological features vary between different regions within the same OSCC, and as histopathological grading is subjective with low reproducibility, the information gained from a single biopsy, particularly if it has been taken from a superficial part of the tumor cannot be used as a reliable indicator of the future clinical behavior of the tumor. , However, it has become clear that the histopathological information gained from multiple biopsies taken from different parts of the invasive front of the cancer has a more significant prognostic value. 
In the population of greater Johannesburg in South Africa, oral leukoplakia occurs significantly more frequently in white than in black persons, , but as this study shows that black and white persons are affected by OSCC more or less equally, it is reasonable to assume that in Johannesburg, OSCC develops de novo more frequently in blacks than in whites. This suggests that in some way the pathogenesis of OSCC may be different in black and white persons. However, it is possible that for educational, cultural, and economic reasons, and because some black persons have less ready access to healthcare facilities, they may delay the seeking of medical advice for leukoplakia, so that by the time of diagnosis, it has already progressed to OSCC.  If indeed some black persons in South Africa seek medical advice late in the course of their disease, the size of their OSCCs at the time of diagnosis would be expected to be larger in blacks than in whites, but to the knowledge of the authors this has not been researched yet.
In 5% (27 persons) of the study population, the OSCCs were new second cancers. For reasons that are uncertain, the proportion of black males (93%) with new second OSCCs was significantly higher than the proportion of white males (58%) with new second OSCCs, perhaps because as has been mentioned some black persons tend to seek medical advice late in the course of their disease. In general, up to 30% of persons with primary OSCCs may develop new second carcinomas.
A new second carcinoma may be a recurrence if it develops from undetected carcinomatous keratinocytes that remained in the margins of the surgical wound despite apparently successful treatment of the primary OSCC. As it is well-established that a primary OSCC is almost always surrounded by a field of precancerized epithelium from which indeed the primary OSCC had arisen and as this field is neither clinically nor histologically detectable, nor is its size determinable, accumulation of additional genetic alterations to keratinocytes within the remaining precancerized field may give rise to a new carcinoma.  The cancerous keratinocytes of the new carcinoma may have a genetic profile similar to that of the cancerous keratinocytes of the primary carcinoma if they both descended from subclones originating from a proliferating monoclone; or they may have dissimilar genetic profiles if they originated from different proliferating clones within the precancerous field. 
OSCC is relatively uncommon in persons of 40 years of age and younger. Only 4-6% of all OSCCs have been reported in this population subgroup, with males being more frequently affected than females, and with the tongue being the most commonly involved site. ,,, However, in recent years there has been an increase in the reported incidence of OSCC affecting the tongue in younger persons, particularly in females. ,,, It has been found that in a South African population sample, about 7.5% of persons with OSCC are younger than 45 years at the time of diagnosis of their OSCC. 
In a recent study from Brazil,  about 11% of all OSCCs occurred in younger persons. In our study, 6% of OSCCs occurred in persons younger than 40 years of age, males more frequently than females. In this subgroup, overall the tongue was the most frequently affected oral site. However, in both younger and in older whites, in contrast to blacks, the floor of the mouth was the most frequently involved site, in line with a recent report from Germany.  A comparative analysis of OSCC in persons of 40 years of age or younger and those of older than 40 years of age is shown in [Table 3].
Muller et al., 2008, reported that SCC of the lip is seen more frequently in younger than in older persons. Likewise in our study, the lip was found to be significantly more frequently affected in younger than in older persons. This finding is surprising as one would have expected that sun-induced damage and consequent possible malignant change would occur more frequently in older than in younger persons, because the former would have been exposed longer to ultraviolet (UV) radiation than the latter.  Even more surprising is the finding that there is no statistically significant difference in the frequency of SCC of the lower lip in younger blacks and younger whites, despite the well-established protective effects of melanin against UV-radiation in blacks. This may be related to the not infrequent eversion of the lower lip in black persons with exposure of part of the labial mucosa to sunlight.
There is some debate regarding the prognosis of OSCC in younger persons.  While some studies have shown that the prognosis is similar in younger and in older persons, ,,, other studies have found that sometimes OSCCs in younger persons are particularly aggressive and are associated with a poor prognosis; ,,, yet other studies have reported rather better survival rates in younger persons than in older persons with OSCC. ,,,
The racial disparities with regard to age, gender, and degree of histopathological differentiation of the OSCCs in our study of a South African population sample are brought about by a complex interaction of factors. The effects of cancer susceptibility genes, exposure to environmental or occupational carcinogens, high-risk lifestyle factors predisposing to OSCC, cultural practices such as consulting traditional healers as opposed to conventional medical practitioners, educational level, socioeconomic status, and lack of convenient accessibility to healthcare services are some of the important factors that could have a bearing on the promotion and clinical course of OSCC. ,,,
Our study has some limitations. Firstly, in the younger subgroup the small number of cases does not allow the identification of meaningful differences between blacks and whites in relation to clinical and histopathological parameters. Secondly, because of the lack of data about the use of tobacco, alcohol, and possible areca nut, we could not make any associations between these risk factors and OSCC either in black or white persons. Thirdly, this retrospective study does not provide accurate information on the global prevalence of OSCC in black and white South Africans because the data was obtained from histopathological records of a single hospital, with the associated referral bias.
However, this study provides some new information about OSCC in younger and older South Africans, and sheds light on some differences in clinical and histopathological features of OSCC in black and white persons.
In summary, the results of this study show that there are significant differences with regard to age and gender between black and white South Africans in the greater Johannesburg area. Further studies aimed at identifying differences in tobacco/betel/areca nut use, alcohol consumption, sexual practices, diet, family history of cancer, and the general health status of persons with OSCC, may shed light on the racial- or ethnic-specific factors that play a role in the pathogenesis of OSCC, and may aid in the development of public health measures aimed at detecting OSCC in its early stages and reducing its incidence.
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[Table 1], [Table 2], [Table 3]