Limited information exists on the clinicopathological characteristics and treatment outcomes specific to leukoplakia of the dorsum of the tongue. Dorsal tongue leukoplakia has not been specifically addressed in the post research and was usually incorporated into the OL of all parts of oral cavity. Therefore, the present study is the first to analyze the clinicopathological features and therapeutic effects of CO2 laser on the dorsal tongue leukoplakia. In addition, we made a comparison between the dorsal and ventrolateral tongue leukoplakia to investigate if there were differences, which is also addressed for the first time in the literature. Our series showed that there were no significant differences of clinicopathological features between the dorsal and ventrolateral tongue leukoplakia, including gender, age, body mass index, history of head and neck cancer, alcohol drinking, cigarette smoking, betel quid chewing, diabetes mellitus, taking metformin, concomitant occurrence of leukoplakia on the other parts of the oral mucosa, Candida infection, area of the lesions, and pathology, except prevalence (P < 0.001). Twenty-seven patients with 39 lesions (3.59%, Fig. 3) of dorsal tongue leukoplakia were enrolled in our series over a period of 17 years. Compared with the cases of ventrolateral tongue leukoplakia (12.08%, 91 patients with 147 lesions, Fig. 3), the prevalence of the dorsal tongue leukoplakia was significantly less than that of the ventrolateral leukoplakia (P < 0.001, odds ratio 2.81, 95% CI 2.03–3.88, Table 3). In other words, the dorsal tongue leukoplakia is not as frequently encountered clinically as the ventrolateral leukoplakia. A similar finding was also noted in another study, where only 3 cases of dorsal tongue leukoplakia were found among 38 lesions . The same phenomenon seems to exist in patients with squamous cell carcinoma of the tongue. Carcinoma of the dorsum of the tongue occurs in 3‒5% of all cases of tongue carcinoma, which is far less frequently seen than ventrolateral tongue carcinoma [9, 19, 20]. The prognosis of the dorsal tongue carcinoma was worse in a study carried out in Hong Kong in 65 tongue cancer patients treated by surgery. The 5-year survival rate of patients with the ventrolateral tongue cancer was 51%, whereas the 5-year survival rate for the dorsal tongue cancer was 0% . On the contrary, as for the treatment outcomes of mobile tongue leukoplakia in the present study, the prognosis in these two sites was not significantly different, including the postoperative recurrence rate (11.11% vs. 14.29%, P = 1.0), cumulative malignant transformation rate (7.41% vs. 2.25%, P = 0.22), and ATR (2.32% vs. 0.64%, P = 0.099, Table 3).
In a meta-analysis of 24 studies of OL treated with CO2 laser, the overall cumulative malignant transformation rate was 4.5% . Another systematic review of 24 articles about malignant development of carcinoma of OL demonstrated that the estimated overall cumulative malignant transformation rate was 3.5% . In the present study, the overall cumulative malignant transformation rate of the oral tongue leukoplakia was 3.6%, and the individual cumulative transformation rates of the dorsal tongue and ventrolateral tongue leukoplakia were 7.41% and 2.25%, respectively (Tables 1, 3), which seemed to be higher than the rate of OL of all subsites of the oral cavity in combination in previous studies. It is not possible to predict when OL will undergo malignant transformation, but it is agreeable that the longer the follow-up, the higher the rate of malignant change. ATR, which is calculated as the transformation rate divided by the time needed for OL to develop into carcinoma, could be a more scientific method to investigate the issue of malignant transformation. The time for OL to develop into carcinoma is a critical factor. If the follow-up time is short, it may not be possible to collect those cases who will transform in the future, and it is likely to underestimate the cumulative transformation rate. In a nationwide population-based retrospective cohort study of 1,898 OL patients in Taiwan, the mean time to develop oral cancer was 2.5 years . A study done in the US showed that the time to the event of malignant change could be shortened because of patient selection bias in a tertiary center . In the studies on OL across the globe, the mean time for malignant transformation ranged from 2 to 8.1 years [4, 25,26,27,28,29,30,31]. In the present study, the mean time for developing carcinoma was 3.35 years, which was consistent with previous research. The time to develop carcinoma from the dorsal tongue leukoplakia was shorter than the ventrolateral tongue leukoplakia (3.19 ± 1.94 vs. 3.51 ± 2.12 years) but the difference didn’t reach a significant difference (P = 0.83, Table 3). In this study, the ATR of the dorsal tongue and ventrolateral tongue leukoplakia of this study was 2.32% and 0.64%, respectively. The ATR of the published works of OL was between 1.2 and 2.9% [32,33,34]. The ATR of dorsal tongue leukoplakia was comparable to that reported in previous studies, but the ATR of ventrolateral tongue leukoplakia was lower. However, the differences between ATRs were not statistically significant (P = 0.099, Table 3). In the multivariate logistic regression analysis, the location of leukoplakia on the tongue was not a significant factor related to postoperative malignant transformation, either (Table 4). The oral tongue has been regarded as a region with a higher risk for the development of carcinoma from leukoplakia [5, 6, 35, 36]. According to the analysis in this study, the ATR of oral tongue leukoplakia in the present study did not seem to be higher than in previous studies. Considering the differences in the treatment modalities, geographical locations, cultural lifestyles, and oral and dietary habits of the patient population studied, the comparison of ATRs may not be on a comparable basis. Hence, the inherent characteristics of different studies should be considered before a conclusion is reached.
In the multivariate logistic regression analysis, pathology was the only independent prognostic factor associated with postoperative malignant transformation of oral tongue leukoplakia (OR 4.58, 95% CI 1.04–20.24, P = 0.045, Table 4). The pathology of OL consists of squamous hyperplasia with hyperkeratosis, and mild, moderate, and severe dysplasia. In a systemic review and meta-analysis of pooled data from 14 cohort studies, the grade of dysplasia was found to be significantly related to the development of malignant transformation , which was consistent with the findings in the present study. Clinicians should pay more attention and take a more aggressive attitude toward the tongue leukoplakia with higher grades of dysplasia.
Whitish patches on the tongue are usually asymptomatic but they are not easily overlooked, so delayed diagnosis does not seem to occur on the oral tongue leukoplakia, regardless of the subsites. Although dysplasia is not infrequently seen in lesions of leukoplakia, epithelial changes are still confined above the basement membrane. Although there are differences in the incidence, morphology, histological architectures, and functions between the dorsal and ventrolateral tongue, we speculate that the relatively benign nature of leukoplakia of both subsites is well subject to laser surgery so the treatment outcomes were not different. Dorsal tongue leukoplakia is not commonly seen clinicall; the reasons why the occurrence of leukoplakia on the specialized epithelium of the dorsal tongue remains an interesting and unsolved topic that needs further investigations in the future .
There are some limitations in this study. First, the sample size of the dorsal tongue leukoplakia was relatively small compared with that of the ventrolateral tongue leukoplakia. Large-scale, multicenter, prospective cohort studies are warranted to further investigate the disease. Second, there were some missing data in the variables due to its retrospective nature. Third, the quality histopathological diagnosis of the tissue might be more or less affected due to the thermal injury of the CO2 laser. Although we chose excision of the whole lesion of the tongue leukoplakia instead of vaporization, the case(s) were excluded when the pathologists could reach a consensus on the pathological diagnosis.