|Year : 2019 | Volume
| Issue : 1 | Page : 129-135
Prevalence of malignant melanoma in anatomical sites of the oral cavity: A meta-analysis
Diksha Singh1, Pragya Pandey2, Manish Kumar Singh3, Shailesh Kudva4
1 Department of Oral and Maxillofacial Pathology, King George's Medical University, Lucknow, Uttar Pradesh, India
2 Department of Conservative Dentistry and Endodontics, King George's Medical University, Lucknow, Uttar Pradesh, India
3 Department of Community Medicine, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
4 Department of Oral and Maxillofacial Pathology, Srinivas Institute of Dental Sciences, Mangalore, Karnataka, India
|Date of Submission||20-Sep-2018|
|Date of Acceptance||29-Dec-2018|
|Date of Web Publication||17-Apr-2019|
Department of Oral and Maxillofacial Pathology, King George's Medical University, Shah Mina Road, Lucknow, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Oral malignant melanoma (OMM) is a very rare disease entity accounting <1% of all other melanomas. Till date, no comprehensive meta-analysis has been conducted regarding the prevalence of malignant melanoma in the oral cavity. Therefore, the present meta-analysis was conducted to update on the prevalence of malignant melanoma in anatomical sites of the oral cavity. Literature search was performed to congregate reports of last 10 years using databases, such as PubMed and ScienceDirect. The search strings used were “palate,” “buccal,” “gingiva,” “gum,” “maxillary,” “mandibular,” “lip,” “tongue,” “melanoma,” “oral melanoma,” “malignant melanoma,” “prognosis,” “risk factors,” “noncutaneous” and “diagnosis” of OMM by combining terms using the Boolean operators. MedCalc 16.4.3 software was used for the analysis. “Random effects model” was used in the analysis due to significant heterogeneity in the studies. Proportion method was used to analyze the prevalence. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to report the analysis. Out of 130 studies screened, 19 were included in the meta-analysis and a total of 1323 patients were included. The median age of the patients was found to be 61.87 ± 7.78 years (confidence interval 53.8–67 years). All the screened studies showed significant heterogeneity in gender as well as tumor sites (P < 0.0001). Palate (34.29%) was the most commonly affected site in OMM patients. Overall, the results of the meta-analysis suggest that palate is the most prevalent site in OMM. Furthermore, OMM is high in patients between the fifth and sixth decade of life with a male predominance.
Keywords: Gingiva, meta-analysis, oral malignant melanoma, oral mucosa, palate, proportion, tumor
|How to cite this article:|
Singh D, Pandey P, Singh MK, Kudva S. Prevalence of malignant melanoma in anatomical sites of the oral cavity: A meta-analysis. J Oral Maxillofac Pathol 2019;23:129-35
|How to cite this URL:|
Singh D, Pandey P, Singh MK, Kudva S. Prevalence of malignant melanoma in anatomical sites of the oral cavity: A meta-analysis. J Oral Maxillofac Pathol [serial online] 2019 [cited 2019 Sep 20];23:129-35. Available from: http://www.jomfp.in/text.asp?2019/23/1/129/256436
| Introduction|| |
Melanoma is a highly aggressive tumor of melanin -producing cells called melanocytes derived from the neural crest cells in the basal layer of the epithelium. It predominantly occurs in cutaneous surfaces and rarely in the ocular ball and mucosal surfaces. Oral malignant melanoma (OMM) is a highly rare malignancy accounting for only 0.5% of all oral malignancies and <1% of all other melanomas.,
OMM is usually asymptomatic in the early stages. Pain, bleeding and ulceration occur at advanced stages of OMM. Owing to its low incidence rate and poor prognosis, the exact treatment modality is not well established. Surgery is the only treatment modality available for this malignancy. The overall 5-year survival rate of this disease is ~6.6%–40%. The frequency of OMM was high among Indians, Africans, Americans, Japanese, Caucasians and Chinese due to increased melanin pigmentation in the oral mucosa.,
OMM has a higher tendency to metastasize to other underlying tissues as compared to other malignancies of the oral cavity. The exact pathogenesis involved in the occurrence of OMM is inadequately understood. However, it is documented that melanocytes migrate to both the ectodermal and endodermal mucosa in OMM. Significant etiological factors are not known for OMM; however, literature has reported that alcohol consumption, tobacco use, cigarette smoking and denture irritation may play a significant role in the occurrence of OMM. From distinct to cutaneous melanoma, OMM has different etiology, histopathology, genetic alterations and prognosis. However, recent research has revealed the expression of BAP1 (BRCA1-associated protein, a BReast CAncer gene) in OMM patients.
On the contrary to cutaneous melanoma, studies have reported that males and individuals aged between 50 and 70 years are prone to OMM.,, Studies have reported that palate and buccal gingiva are the most common sites of OMM; other sites include the floor of the mouth, buccal mucosa, lips and the tongue. To the best of our knowledge, there has been no comprehensive analysis including age, gender and different tumor sites in OMM. Therefore, the present meta-analysis was conducted to update on the prevalence of malignant melanoma in different anatomical sites of the oral cavity.
| Materials and Methods|| |
Literature search strategy
The research articles, case reports and randomized controlled trials published between 2008 and 2018 were screened using databases such as PubMed and ScienceDirect. The search strings used were “palate,” “buccal,” “gingiva,” “gum,” “maxillary,” “mandibular,” “lip,” “tongue,” “melanoma,” “oral melanoma,” “malignant melanoma,” “prognosis,” “risk factors,” “non-cutaneous” and “diagnosis of OMM” by combining terms using the Boolean operators. All the studies were screened after reading the title and abstract. Literature review was completed within a period of 1 month (June 2018 – July 2018). The information on name of the first author, year of publication, outcome, age group considered, gender evaluated and tumor sites diagnosed were extracted from all the articles selected for the study. Two investigators independently assessed the articles and the disagreements if any were resolved by a third investigator, after discussion.
Inclusion and exclusion criteria
The study was approved by the institutional ethics committee. Full-text articles published in English language were included in the analysis. All the studies consisting of immunohistochemistry confirmed OMM patients of all ages were included in the analysis. Review and meta-analysis articles published in other languages were omitted from the analysis. Meeting abstracts, letters and nonhuman studies were excluded. Inadequately designed studies, low-quality data and OMM studies with nonspecific and multiple tumor sites were also exempted from the analysis. Preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed to report the analysis.
MedCalc 16.4.3 (Ostend, Belgium) software was used to analyze the data. Proportion method was performed, and forest plot was derived for meta-analysis. The proportion of patients was analyzed at a 95% confidence interval (CI). Cochrane Q statistics were used to ascertain the presence of heterogenicity within the selected articles. Random effects model (DerSimonian and Laird method) was used in the analysis due to the presence of significant heterogeneity. The 95% CI for the median age was calculated using the binomial probability.
| Results|| |
The detailed literature search process is represented in the PRISMA flow diagram [Figure 1]. After a detailed assessment, 19 studies were selected, which consisted of 1324 patients diagnosed with OMM and were used for the analysis of age and gender. In the analysis of the tumor site, three studies were excluded due to insufficient data; the total sample size for the analysis was reduced to 1277.
|Figure 1: Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram showing the total number of included studies|
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Of the total 1324 patients, 55.63% were males and 44.36% were females. A significant heterogeneity in gender was observed in the screened studies (I2 = 45.74% with CI 5.77%–68.75%, P = 0.01). The average proportion of male and female patients in the study was 56.10% (CI 51.74–60.43) and 43.89% (CI 39.57%–48.25%), respectively. Out of 19 studies, 12 studies reported the proportion of males and females between 50%–70% and 30%–50%, respectively.
The weighed median age of the patients in the screened studies was 61.87 ± 7.78 years (CI 53.8–67 years). Out of 19 studies assessed, the median age of OMM patients in six studies was above the calculated age and the remaining 13 studies reported below the calculated age.
Of the 19 screened studies, three studies were excluded from the analysis due to unspecified tumor site. Therefore, only 16 studies comprising of 1277 patients were included in the meta-analysis regarding the tumor site. All the screened studies reported significant heterogeneity (P < 0.0001) in the primary tumor sites (palate, gingiva, buccal mucosa, tongue, mandible gum, maxillary gum and lips). Palate (34.29% with CI 24.54%–44.75%) was the most commonly affected site in OMM patients [Figure 2]. The other affected sites included the gingiva (8.88% with CI 1.73%–20.76%), buccal mucosa (4.38% with CI 1.91%–7.79%), tongue melanoma (2.30% with 0.92%–4.28%), maxillary gum melanoma (7.06% with CI 2.17%–14.46%), mandibular gum melanoma (3.63% with CI 1.00%–7.81%) and lips [1.50% with CI 0.44%–3.17%; [Figure 3], [Figure 4], [Figure 5].
|Figure 3: Forest plot for the prevalence of (a) gingival and (b) buccal melanoma|
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|Figure 4: Forest plot for the prevalence of (a) tongue and (b) mandibular gum melanoma|
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|Figure 5: Forest plot for the prevalence of (a) maxillary gum and (b) lip melanoma|
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| Discussion|| |
OMM is a very rare disease entity. Age, gender, race, tumor site, stage of disease and treatment are different factors that influence the survival of OMM patients. OMM has been stable from past 25 years, hence, the present study intended to update the recent prevalence. Moreover, this is the first study of its kind assimilating and analysing all the prominent anatomical sites that are prone to OMM. The update of the recent prevalence also lay down recommendations for future research. Therefore, through detailed meta-analysis on the latest literature, we assimilated and provided the prevalence of malignant melanoma in different anatomical sites of the oral cavity. In addition to tumor site, we also focused on the prevalence of OMM in both age and gender.
Literature has reported a higher prevalence of OMM among men. Similarly, our meta-analysis also revealed the male to female ratio of 1:0.78. Male prevalence (33.33%) was lowest in a study conducted by Umeda et al. with a sample size of 21; whereas, Baderca et al. reported highest prevalence (80%) with a sample size of five. Sortino-Rachou et al. reported highest male (54.54%) and female (45.45%) prevalence with a sample size of 319. In contrast, Smith et al. (62.50%) and Umeda et al. (66.66%) reported a high prevalence of OMM in women. Moreover, in a study by Kim et al., sex predilection was not observed in OMM patients. The probable reason for the higher prevalence of OMM in males might be due to alcohol and tobacco consumption and smoking. However, there is a lack of literature to support this observation. Therefore, the exact cause for gender disparity is still to be explored in future studies. Furthermore, studies should also focus on correlation between habits (smoking and alcohol consumption) and OMM.
Age is considered as the prognostic indicator for OMM. Similarly, our meta-analysis also reported an age range of 50–70 years. Highest (73 years) and lowest (51.5 years) median ages were observed in two different studies conducted by Baderca et al. (with a sample size of five) and Wang et al., respectively. However, the median age of the patients in all the studies was in-between 50 and 75 years. Late clinical manifestations, slow progression of the disease and patients with the history of radiation or chemotherapy for other carcinomas are the probable reasons for late diagnosis and high incidence of OMM in advancing age., However, few studies showed the prevalence of OMM both in children as well as in young adults.,,,
The anatomical sites affected with OMM were observed to be palate, gingiva, buccal mucosa, tongue, mandible and maxillary gum and lips in our meta-analysis. Most of the studies screened in our meta-analysis reported palate as the commonly affected tumor site in OMM patients. The highest prevalence of palate melanoma was observed in a study by Umeda et al., wherein 21 patients were included. It was reported that anterior regions of the mouth were extensively pigmented than the posterior regions; therefore, buccal/labial regions are intensely pigmented than the palatal/lingual surfaces. Nevertheless, literature has reported that palate was the most common site involved in OMM with an overall prevalence of 32%–40%. Similarly, our meta-analysis reported palate melanoma in 34.29% patients. In contrast, few studies reported gingiva as the most commonly affected tumor site in OMM patients., In our analysis, the highest prevalence of gingival melanoma was observed in a study by Sun et al., who included 51 patients. However, the overall prevalence of patients with gingival melanoma (8.88%) was less than that reported in the literature, i.e., 16%.
Other than palate and gingiva, mandible, maxilla, tongue and buccal mucosa are the most prominent sites for metastatic melanoma; however, the prevalence of patients presenting with malignant melanoma in these sites is low in our analysis. In our meta-analysis, the overall prevalence of patients with buccal mucosal melanoma (4.38%) was less than that reported in the literature, i.e., 7%. The exact prevalence of patients with maxillary gum melanoma, mandibular melanoma and tongue melanoma was not specified in the literature. In our meta-analysis, overall prevalence of tongue melanoma, maxillary gum melanoma and mandibular gum melanoma was 2.30%, 7.06% and 3.63%, respectively.
Literature has reported that lip was the least possible site for the incidence of OMM. Similarly, in our meta-analysis, the overall prevalence of patients with lip melanoma was very less (1.50%) than reported in the literature, i.e., 7%. The least incidence of melanoma in the lip region might be due to the absence of melanocytes. Whereas, a study conducted by Jing et al. was exclusively on the melanoma in subregions of the lip. Over the period of 20 years, i.e., 1992–2013, only 48 cases of lip melanoma were recorded, which indicates the rarity of lip melanoma.
Anatomical site is another prognostic indicator, which correlates significantly with the overall survival rate of OMM patients. A study conducted by Wang et al. reported that the overall median survival rate among OMM patients with different tumor sites were 51, 40 and 43 months for gingiva, hard palate and other sites, respectively. The higher survival rate in gingiva-affected OMM patients might be due to its easy prognosis.
The current meta-analysis has few potential limitations that need to be considered in the future analyses. First, free full-text articles restricted to only English language were screened for the analysis. Second, a subgroup analysis of anatomical sites was not performed as it was not mentioned in all the studies. Third, analysis was not done regarding symptoms, etiological factors, treatment and therapy standards as the data were not available/clear in the screened studies. Fourth, most of the screened studies were from China and few were conducted in Japan and the United States of America; hence, this might produce selection bias. Despite these limitations, the current meta-analysis is the first study of its kind that determined the prevalence of malignant melanoma with respect to age, gender and tumor sites.
Till date, etiological/risk factors involved in the development of OMM has not been identified. Genetic studies revealed that either carcinogenic factors or other irritants have not shown any influence on the pathogenesis of OMM. Therefore, in the future, studies need to be conducted to identify risk factors that cause OMM. However, few studies have reported that BRAF mutation/expression was involved in the pathogenesis of OMM., Therefore, further research is desired in gene mutations for molecular classification of OMM. This, in turn, aids in the better prognosis of the disease in the early stages. Furthermore, research needs to determine the biological factors that influence the treatment of OMM to improve overall survival of OMM patients.
| Conclusion|| |
Our meta-analysis has reassessed and reported that palate is the most prevalent site in OMM patients in advancing age with male predominance. Our analysis has not focused on gene alterations, targeted therapies and survival rate. Therefore, this analysis may open the door for further research to determine other prognostic indicators, gene mutations and biomarkers and evaluate the risk factors involved in the development of OMM.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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