Photodynamic therapy (PDT) for oral leukoplakia: a systematic review and meta-analysis of single-arm studies examining efficacy and subgroup analyses

Zhang et al. BMC Oral Health (2023) 23:568 https://doi.org/10.1186/s12903-023-03294-3 BMC Oral Health Open Access RESEARCH Photodynamic therapy (PDT) for oral leukoplakia: a systematic review and metaanalysis of single-arm studies examining efficacy and subgroup analyses Rui Zhang1*, Tong Gao2 and Dan Wang3 Abstract Objective This study aims to evaluate the efficacy of photodynamic therapy (PDT) in the treatment of oral leukoplakia and explore the subgroup factors that may influence its effectiveness. Methods A systematic search was conducted in PubMed, Embase, the Cochrane Library, and Web of Science databases to identify relevant studies. Meta-analysis was performed using Stata15.0 software. Cochran’s Q test and I2 statistics were used to evaluate heterogeneity, egger’s test was used to evaluate publication bias. Results The analysis of 17 studies included in this study suggests that PDT may be effective in achieving complete response (CR) [ES = 0.50, 95%CI: (0.33,0.66)], partial response (PR) [ES = 0.42, 95%CI: (0.27,0.56)], no response (NR) [ES = 0.19, 95%CI: (0.11,0.27)]in patients with oral leukoplakia. The recurrence rate was also evaluated [ES = 0.13, 95%CI: (0.08,0.18)]. Subgroup analysis showed that various factors such as light source, wavelength, medium, duration of application, clinical and pathological diagnosis classification influenced efficacy of PDT. The lesion areas of the leukoplakia after treatment were reduced by 1.97cm2 compared with those before treatment. Conclusion Our findings show that PDT is a viable treatment for oral leukoplakia. However, the effectiveness of the therapy may depend on several factors, as suggested by our subgroup analyses. (Registration no. CRD42023399848 in Prospero, 26/02/2023) Keywords Photodynamic therapy, Oral leukoplakia, meta-analysis, Single arm, Subgroup analysis *Correspondence: Rui Zhang 1 Department of General Stomatology, General Hospital of Ningxia Medical University, Yinchuan 750004, China 2 Department of Prosthodontics, Affiliated Hospital of Yanan University, Shaanxi 716000, China 3 Department of Stomatology, Qingtongxia Hospital of Traditional Chinese Medicine, Ningxia 751600, China © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Zhang et al. BMC Oral Health (2023) 23:568 Introduction Leukoplakia is a white lesion in the oral mucosa, excluding other white lesions that can be diagnosed clinically, histopathologically, and by auxiliary means, and is usually non-erasable [1]. The etiology of leukoplakia is not fully understood, but chronic local irritation, smoking, and areca nut chewing are considered possible causes. Oral leukoplakia is a common and potentially malignant oral disease, with a high risk of progressing to squamous cell carcinoma. The global incidence of oral leukoplakia is 4.11% [2]. Clinicopathological and systematic review studies indicate that oral leukoplakia’s malignant transformation rate is 7.5% and 9.7%, respectively. In clinical studies, although some cases of leukoplakia had clinically benign features, some parts of the tissues were found to have transformed into malignant lesions by further histopathological examination [3, 4]. Since leukoplakia is a precancerous lesion that can cause systemic health effects if left untreated, certain studies have documented its associations with an increased risk of upper gastrointestinal cancers [5, 6]. Therefore, prompt treatment of oral leukoplakia is critical. Traditional methods for treating leukoplakia include systemic drug application and local surgical excision. However, these therapies have significant drawbacks, including drug side effects and tissue defects after surgery. Therefore, cryotherapy, laser, and photodynamic therapy (PDT) have become increasingly common in clinical practices [7, 8]. PDT is a minimally invasive treatment that uses exogenous light and photosensitizers to sensitize tumor tissue to specific light wavelengths. Activation of photosensitizers in tissues by these wavelengths creates reactive oxygen species (ROS) by transferring energy from the light to molecular oxygen [9, 10]. The destruction of tumors mediated by PDT occurs through three main mechanisms. Firstly, ROS directly kill tumor cells. Secondly, PDT can disrupt the vascular system associated with the tumor, leading to thrombosis and subsequent tumor infarction. Finally, PDT can lead to an immune response against tumor cells [9]. PDT has several advantages over traditional treatments: it is less invasive, causes fewer side effects than systemic medication, and is more precise in targeting the lesion while preserving normal tissues. Nowadays, PDT therapy has been widely used to treat oral diseases, including leukoplakia [11–14]. However, existing reports differ in the types of medium, duration of application, light source, and wavelength used, among other factors. There is no standard reference for clinical practice. Therefore, this study aims to conduct a meta-analysis on the efficacy of PDT in treating oral leukoplakia, comparing various factors that may influence its effectiveness. The results of this study are expected to guide clinical practice. Page 2 of 14 Materials and methods This systematic review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. The detailed PRISMA checklist shown in Additional File 1 Table S1. Search strategy We comprehensively searched the PubMed, Embase, the Cochrane Library, and Web of Science databases from inception to January 29, 2023. The search keywords were “Leukoplakia, Oral” and “Photochemotherapy”. The search strategy includes subject terms and free words. The specific search strategy in PubMed was as follows: (((“Photochemotherapy“[MeSH Terms] OR (“Photochemotherapy“[Title/Abstract] OR “Photochemotherapies“[Title/Abstract])) AND ((“leukoplakia, oral“[MeSH Terms] OR (“leukoplakia oral“[Title/ Abstract] OR “leukoplakia (...truncated)