In this study, the malignant transformation rate of OLP was 0.7%. The overall average malignant transformation rate cited in six recent systematic reviews and meta-analyses [9–14] was 1.09%. Our percentage is slightly lower than the overall average percentage. However, Idrees et al [14] showed the lowest malignant transformation rate of 0.44%, indicating that the rates cited by other authors were based on studies that included ineligible cases with nonconfirmed OLP, those with epithelial dysplasia at the initial diagnosis, and those with a follow-up duration of < 6 months. Gonzales-Moles et al [3] suggested that the high incidence of malignant transformation described in many studies might be attributable to the misdiagnosis of some lesions as OLP. Therefore, based on these diagnostic criteria, the malignant transformation of OLP may be ≤ 1%.
The differentiation between OED and OLLs is important for the diagnosis of OLP. OED is a well-known precursor of SCC, and its presence and dysplasia grade influence the malignant transformation potential of OPMDs [15]. Iocca et al [13] reported that the malignant transformation rate of OLP was the lowest in OMPDs, indicating the absence of epithelial dysplasia in OLP. In this study, 3 (3.7%) out of 81 OED patients developed SCC. This rate was considerably higher than the rate in patients with OLP, suggesting a low malignant potential of OLP.
However, Lodi et al [16] noted that lesions with clinical features of OLP but with dysplasia may represent an early phase in the malignant transformation of OLP. Thus, excluding OLP with epithelial dysplasia from these studies may still be debatable.
In this study, no OLL patient developed SCC. However, some studies have reported that OLCLs might possess malignant potential similar to that of OLP [17, 18]. Therefore, regular follow-up is required for OLCL patients with malignant transformation as well as OLL-GVHD patients who are known to be at risk of SCC development. We did not find any OLDR suspected lesions because OLDR can occur at any time during the disease course, even > 1 y after initiating medication. No standard diagnostic criteria for OLDR have been established, and further research on this subject is necessary.
Based on six recent systematic reviews and meta-analyses [9–14], tongue localization, red type (atrophic or erosive pattern), tobacco and alcohol consumption, and HCV infection significantly heighten the risk of the malignant transformation of OLP. In the present study, we could not investigate the clinical risk factors associated with malignant transformation due to the relatively small study population, which did not allow statistically meaningful analyses. However, we found that age ≥ 62 y, lateral tongue site, and red-type OLP tended to have a higher risk of SCC development (Table 2). Further research on this subject is needed.
Regarding age and sex, the risk of the malignant transformation of OLP is believed to be higher in women than in men in the age group of 60–70 y [3]. Demographically, OLP is more common in women aged > 40 y. Furthermore, Gonzales-Moles et al [1] reported a significantly higher prevalence in subjects aged > 50 y or > 60 y. Thus, age and sex associated with the malignant transformation risk were suggested to be linked to demographics.
Regarding the clinical type and site, Aghbari et al [10] reported that the rates of malignant transformation were 1.7%, 1.3%, and 0.1% in erosive, atrophic, and reticular patterns, respectively. The most common site was the tongue (1.05%), followed by the buccal mucosa (0.7%), the gingiva and the lips (0.6%), and the floor of the mouth (0.5%). With respect to the clinical type and site, the results of this study were almost consistent with previous results. In addition, the mean duration until malignant transformation was much shorter in those with red-type OLP than in those with white-type OLP. Red-type OLP was suggested to have a higher malignant potential than white-type OLP.
Research has demonstrated a strong association between HCV infection and OLP, which is explained by the ability of the virus to replicate in oral mucosa cells and attract HCV-specific T lymphocytes [19]. Furthermore, HCV is an oncogenic virus and might be involved in oral carcinogenesis [20]. In our study, 4.4% of the OLP patients had an HCV infection; none developed SCC. Further studies on this subject are required.
The treatment of OLP involves the use of corticosteroids, cyclosporin, azathioprine, and retinoids. However, immunosuppressive agents may trigger malignant transformation, and the treatment of OLP patients with topical and/or systemic steroids did not influence the risk of malignant transformation [16]. Thus, we believe that in our study, the treatment did not affect the risk of malignant transformation.
However, OLP patients have an increased prevalence of Candida infection and are predisposed to candidiasis with topical or systemic immunosuppressive therapy. Candida generates chronic inflammation and can produce carcinogenic N-nitrosobenzylmethylamine [21] and mutagenic amounts of acetaldehyde [22]. Although Candida strongly contributes to carcinogenesis, its association with carcinoma remains unclear. Further studies on this subject that may clarify these limitations are needed.