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Cancers
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Oral Potentially Malignant Disorders and Oral Cavity Cancer
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Oral Potentially Malignant Disorders and Oral Cavity Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 9530

Special Issue Editor

Dr. I-Ta Lee

E-Mail Website
Guest Editor
School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 110301, Taiwan
Interests: signaling transduction; inflammation; cancer; antioxidants; anti-inflammation; anti-cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue in the journal Cancers is dedicated to the in-depth exploration of oral potentially malignant disorders (OPMDs) and oral cavity cancer, focusing on clinical, molecular, and translational aspects. We invite contributions from experts in the field, covering topics such as the clinical characteristics, pathology, molecular biology, and genomics of OPMDs. This Special Issue emphasizes key events in the transition of OPMDs to oral cavity cancer, with a particular focus on gene variations, protein abnormalities, and cellular signaling pathways associated with pathogenesis. Additionally, we welcome research on novel diagnostic tools, imaging techniques, and therapeutic strategies to enhance the precision of early detection and treatment. This Special Issue seeks contributions that provide new insights and approaches to the treatment of OPMDs and oral cavity cancer, including advancements in personalized therapy, immunotherapy, and targeted treatments. Ultimately, we aim to advance a more comprehensive and in-depth understanding of these disorders, fostering translational medicine and precision healthcare in clinical practice.

In this Special Issue, we enthusiastically invite the submission of original research articles and reviews. We welcome contributions across a broad spectrum of research areas, including but not limited to the following:

  • Clinical characteristics of oral potentially malignant disorders (OPMDs);
  • Molecular mechanisms underlying the progression of OPMDs to oral cavity cancer;
  • Advances in diagnostic imaging technologies for early detection;
  • Biomarkers for predicting the risk and progression of oral cavity cancer;
  • Therapeutic approaches and novel interventions for OPMDs and oral cavity cancer;
  • Genomic and proteomic studies informing precision medicine in oral oncology;
  • Immunotherapeutic strategies and immune microenvironment in oral cavity tumors;
  • Translational research bridging bench to bedside in oral cancer;
  • Patient stratification and personalized treatment plans;
  • Emerging trends and future perspectives in oral oncology research.

We look forward to receiving your valuable contributions to this Special Issue.

Dr. I-Ta Lee
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • OPMDs
  • oral cavity cancer
  • molecular biology
  • genomics
  • pathology
  • early detection
  • personalized therapy
  • immunotherapy
  • targeted treatment
  • translational medicine

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Published Papers (7 papers)

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Research

Jump to: Review, Other

18 pages, 4987 KiB  
Article
Impacts of Dental Follicle Cells and Periodontal Ligament Cells on the Bone Invasion of Well-Differentiated Oral Squamous Cell Carcinoma
by Anqi Chang, Kiyofumi Takabatake, Tianyan Piao, Takuma Arashima, Hotaka Kawai, Htoo Shwe Eain, Yamin Soe, Zin Zin Min, Keisuke Nakano and Hitoshi Nagatsuka
Cancers 2025, 17(9), 1559; https://doi.org/10.3390/cancers17091559 - 3 May 2025
Abstract
Background: Oral squamous cell carcinoma (OSCC) frequently invades the jawbone, leading to diagnostic and therapeutic challenges. While tumor–bone interactions have been studied, the specific roles of dental follicle cells (DFCs) and periodontal ligament cells (PDLCs) in OSCC-associated bone resorption remain unclear. This study [...] Read more.
Background: Oral squamous cell carcinoma (OSCC) frequently invades the jawbone, leading to diagnostic and therapeutic challenges. While tumor–bone interactions have been studied, the specific roles of dental follicle cells (DFCs) and periodontal ligament cells (PDLCs) in OSCC-associated bone resorption remain unclear. This study aimed to compare the effects of DFCs and PDLCs on OSCC-induced bone invasion and elucidate the underlying mechanisms. Methods: Primary human DFCs and PDLCs were isolated from extracted third molars and characterized by Giemsa and immunofluorescence staining. An in vitro co-culture system and an in vivo xenograft mouse model were established using the HSC-2 OSCC cell line. Tumor invasion and osteoclast activation were assessed by hematoxylin and eosin (HE) and tartrate-resistant acid phosphatase (TRAP) staining. Immunohistochemical analysis was performed to evaluate the expression of receptor activator of NF-κB ligand (RANKL) and parathyroid hormone-related peptide (PTHrP). Results: DFCs significantly enhanced OSCC-induced bone resorption by promoting osteoclastogenesis and upregulating RANKL and PTHrP expression. In contrast, PDLCs suppressed RANKL expression and partially modulated PTHrP levels, thereby reducing osteoclast activity. Conclusions: DFCs and PDLCs exert opposite regulatory effects on OSCC-associated bone destruction. These findings underscore the importance of stromal heterogeneity and highlight the therapeutic potential of targeting specific stromal–tumor interactions to mitigate bone-invasive OSCC. Full article
(This article belongs to the Special Issue Oral Potentially Malignant Disorders and Oral Cavity Cancer)
10 pages, 204 KiB  
Article
The Early Detection of Malignant Transformation of Potentially Malignant Disorders: Oral Lichen Planus
by Camilla Lüdecke, Heinrich Neumann and Torsten W. Remmerbach
Cancers 2025, 17(9), 1489; https://doi.org/10.3390/cancers17091489 - 28 Apr 2025
Viewed by 133
Abstract
Background: The aim of this study was to evaluate the usefulness of close clinical surveillance intervals combined with oral brush biopsies to enable the early detection of malignant transformations in patients with oral lichen planus (OLP) performed in our oral medicine clinic. Methods: [...] Read more.
Background: The aim of this study was to evaluate the usefulness of close clinical surveillance intervals combined with oral brush biopsies to enable the early detection of malignant transformations in patients with oral lichen planus (OLP) performed in our oral medicine clinic. Methods: This retrospective study was carried out on 414 patients suffering from OLP, based on pre-established clinical and histopathological criteria, who received long-term follow-up between 1993–2022 (ranging from 6 months to 22.2 years). Results: A total of 297 patients were included in this study. Four people developed an oral squamous cell carcinoma (OSCC) during the observation period. Patients with close follow-up intervals were detected at early stages (two cases showed histologically SIN III and one patient was classified as having a pT1N0M0 tumour). One case was dropped in the consultation hour during the COVID19 pandemic and appeared again two years later, staged as a pT3N1M0 tumour based on an OLP. Three of the cases were clinically doubtful, which led to brush biopsies. Afterwards, additional DNA-image cytometry was performed, in which all the specimens of brush biopsies showed aneuploidy as a marker for malignancy, regarding both stem line and single cell aneuploidy. Conclusions: A careful surveillance programme consisting of check-ups every 3–4 months, oral brush biopsies, and static DNA image cytometry in cytologically diagnosed doubtful or suspicious cases assures the early detection of malignant transformation in the cancer’s early intraepithelial and microinvasive stages. Full article
(This article belongs to the Special Issue Oral Potentially Malignant Disorders and Oral Cavity Cancer)
10 pages, 1222 KiB  
Article
Association between Periodontitis and Hematologic Cancer: An NHIRD Cohort Study in Taiwan
by Liang-Gie Huang, Cheng-Chia Yu, Ming-Ching Lin, Yu-Hsun Wang and Yu-Chao Chang
Cancers 2024, 16(9), 1671; https://doi.org/10.3390/cancers16091671 - 25 Apr 2024
Cited by 1 | Viewed by 1851
Abstract
Background: Chronic periodontitis, an inflammation-related disorder affecting global populations, has been revealed to be linked to diverse cancers. Numerous epidemiological studies have not shown a link between chronic periodontitis and blood cancers in Taiwan. Methods: This study included 601,628 patients, diagnosed with newly [...] Read more.
Background: Chronic periodontitis, an inflammation-related disorder affecting global populations, has been revealed to be linked to diverse cancers. Numerous epidemiological studies have not shown a link between chronic periodontitis and blood cancers in Taiwan. Methods: This study included 601,628 patients, diagnosed with newly chronic periodontitis by the ICD-9-CM classification, who were enrolled from 2001 to 2021 in the National Health Insurance Research Database (NHIRD) in Taiwan. In this study, we employed comprehensive statistical analyses to investigate the association between chronic periodontitis and hematologic cancers. Initially, we calculated incidence density and used a Poisson regression to analyze relative risk. Subsequently, we compared the cumulative incidence of hematological cancer in both chronic and non-chronic periodontitis groups using the Kaplan–Meier method. Results: The results revealed a significantly lower cumulative incidence of hematologic cancer in individuals with non-chronic periodontitis over a 12-year follow-up period. To further explore the risk factors, a Cox proportional hazard regression analysis was conducted. Being male (adjusted hazard ratio [aHR] = 1.21, 95% CI: 1.04 to 1.42; p = 0.014) and having hypertension (aHR = 1.34, 95% CI: 1.06 to 1.69; p = 0.015) were demonstrated to be associated with an increased risk of hematologic cancers, respectively. In addition, in a subtype multivariate analysis for categorizing hematologic cancers into lymphoma and leukemia, the aHR for leukemia was 1.48 (95% CI: 1.13 to 1.93; p = 0.004) and aHR for lymphoma was 1.15 (95% CI: 0.96 to 1.37; p = 0.140). Conclusions: This study found that being male and having hypertension were the significant risk factors for hematological malignancies. Moreover, the association between chronic periodontitis and specific subtypes of hematologic cancers was confirmed. Full article
(This article belongs to the Special Issue Oral Potentially Malignant Disorders and Oral Cavity Cancer)
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Review

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15 pages, 1486 KiB  
Review
Saliva in Balancing Oral and Systemic Health, Oral Cancer, and Beyond: A Narrative Review
by Kohei Okuyama and Souichi Yanamoto
Cancers 2024, 16(24), 4276; https://doi.org/10.3390/cancers16244276 - 23 Dec 2024
Viewed by 1680
Abstract
Saliva plays a multifaceted role in oral health and systemic well-being. It supports digestion, protects oral tissues, maintains a healthy oral microbiome, and facilitates wound healing. Additionally, saliva serves as a diagnostic tool that reflects systemic health and disease/therapeutic states. Furthermore, although saliva [...] Read more.
Saliva plays a multifaceted role in oral health and systemic well-being. It supports digestion, protects oral tissues, maintains a healthy oral microbiome, and facilitates wound healing. Additionally, saliva serves as a diagnostic tool that reflects systemic health and disease/therapeutic states. Furthermore, although saliva shows a protective effect against oral cancer development, once tumor formation occurs, it may be involved in tumor progression and metastasis via exosomes and microRNAs. This review discusses the essential role of saliva; its relationship with the development, progression, and metastasis of head and neck squamous cell carcinoma (HNSCC); liquid biopsy tools for early diagnosis and monitoring of HNSCC; and the potential of exosomes as therapeutic agents. Full article
(This article belongs to the Special Issue Oral Potentially Malignant Disorders and Oral Cavity Cancer)
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13 pages, 562 KiB  
Review
Estimating the Benefits of Oral Cancer Screening: Challenges and Opportunities
by Francesca Farina and Nicola Cirillo
Cancers 2024, 16(23), 4110; https://doi.org/10.3390/cancers16234110 - 8 Dec 2024
Cited by 1 | Viewed by 1464
Abstract
Screening is widely believed to facilitate early detection and improve health outcomes; however, recent evidence questions its overall benefits, highlighting the need for a critical assessment of cancer screening programs. The simplicity of clinical oral examination and the easy accessibility of the oral [...] Read more.
Screening is widely believed to facilitate early detection and improve health outcomes; however, recent evidence questions its overall benefits, highlighting the need for a critical assessment of cancer screening programs. The simplicity of clinical oral examination and the easy accessibility of the oral cavity make oral cancer a suitable candidate for opportunistic screening. Despite this uniqueness, studies that solidly assess the efficacy and cost-effectiveness of oral cancer screening are scanty, and the only large randomized trial undertaken so far shows limited evidence of mortality reduction through population screening. Research indicates that while early detection rates following screening may increase, they do not necessarily translate into decreased oral cancer deaths. This article emphasizes the need for a nuanced understanding of the benefits of screening, awareness of deceptive metrics and inherent biases in the context of early detection, and the importance of improving dentist education and introducing new technologies to enhance clinical decision-making. The review calls for a balanced and evidence-based approach to oral cancer screening, integrating it with broader oral health initiatives to maximize public health outcomes. Full article
(This article belongs to the Special Issue Oral Potentially Malignant Disorders and Oral Cavity Cancer)
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19 pages, 335 KiB  
Review
A Narrative Review: Repurposing Metformin as a Potential Therapeutic Agent for Oral Cancer
by Jui-Hsiang Li, Pei-Yi Hsin, Yung-Chia Hsiao, Bo-Jun Chen, Zhi-Yun Zhuang, Chiang-Wen Lee, Wei-Ju Lee, Thi Thuy Tien Vo, Chien-Fu Tseng, Shih-Fen Tseng and I-Ta Lee
Cancers 2024, 16(17), 3017; https://doi.org/10.3390/cancers16173017 - 29 Aug 2024
Cited by 4 | Viewed by 1949
Abstract
Oral cancer, particularly oral squamous cell carcinoma (OSCC), is a significant global health challenge because of its high incidence and limited treatment options. Major risk factors, including tobacco use, alcohol consumption, and specific microbiota, contribute to the disease’s prevalence. Recently, a compelling association [...] Read more.
Oral cancer, particularly oral squamous cell carcinoma (OSCC), is a significant global health challenge because of its high incidence and limited treatment options. Major risk factors, including tobacco use, alcohol consumption, and specific microbiota, contribute to the disease’s prevalence. Recently, a compelling association between diabetes mellitus (DM) and oral cancer has been identified, with metformin, a widely used antidiabetic drug, emerging as a potential therapeutic agent across various cancers, including OSCC. This review explores both preclinical and clinical studies to understand the mechanisms by which metformin may exert its anticancer effects, such as inhibiting cancer cell proliferation, inducing apoptosis, and enhancing the efficacy of existing treatments. Preclinical studies demonstrate that metformin modulates crucial metabolic pathways, reduces inflammation, and impacts cellular proliferation, thereby potentially lowering cancer risk and improving patient outcomes. Additionally, metformin’s ability to reverse epithelial-to-mesenchymal transition (EMT), regulate the LIN28/let-7 axis, and its therapeutic role in head and neck squamous cell carcinoma (HNSCC) are examined through experimental models. In clinical contexts, metformin shows promise in enhancing therapeutic outcomes and reducing recurrence rates, although challenges such as drug interactions, complex dosing regimens, and risks such as vitamin B12 deficiency remain. Future research should focus on optimizing metformin’s application, investigating its synergistic effects with other therapies, and conducting rigorous clinical trials to validate its efficacy in OSCC treatment. This dual exploration underscores metformin’s potential to play a transformative role in both diabetes management and cancer care, potentially revolutionizing oral cancer treatment strategies. Full article
(This article belongs to the Special Issue Oral Potentially Malignant Disorders and Oral Cavity Cancer)

Other

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16 pages, 2179 KiB  
Systematic Review
Predictive Value of the Loss of pRb Expression in the Malignant Transformation Risk of Oral Potentially Malignant Disorders: A Systematic Review and Meta-Analysis
by María López-Ansio, Pablo Ramos-García and Miguel Ángel González-Moles
Cancers 2025, 17(2), 329; https://doi.org/10.3390/cancers17020329 - 20 Jan 2025
Viewed by 792
Abstract
Objective: The aim of this systematic review and meta-analysis was to qualitatively and quantitatively evaluate the current evidence on the significance of the loss of early stages of oral carcinogenesis in lesions diagnosed according to clinical and/or histopathological criteria and their evolution to [...] Read more.
Objective: The aim of this systematic review and meta-analysis was to qualitatively and quantitatively evaluate the current evidence on the significance of the loss of early stages of oral carcinogenesis in lesions diagnosed according to clinical and/or histopathological criteria and their evolution to oral cancer. Materials and Methods: We searched MEDLINE (through PubMed), Embase, Scopus and Web of Science for primary-level studies published before November 2024, designed as prospective or retrospective longitudinal cohorts, and not restricted by language or publication date. The risk of bias was critically assessed using the QUIPS tool. Meta-analyses, heterogeneity exploration, sensitivity and small-study effect analyses were conducted. Results: The inclusion criteria were met by six primary-level studies, which recruited 330 patients with OPMDs with follow-up data. The loss of pRb expression, assessed through immunohistochemistry, was significantly associated with a higher malignant transformation risk of OPMDs (RR = 1.92, 95%CI = 1.25–2.94, p = 0.003). The leukoplakia subgroup retained this significant association (p = 0.006), being the OPMD where the loss of pRb expression showed the best predictive value for malignant transformation (RR = 2.00, 95%CI = 1.22–3.29). Regarding the immunohistochemical technique and scoring methods, better performance and results were achieved by applying a cutoff point > 10% pRb-positive cells with nuclear staining (RR = 2.10, 95%CI = 1.30–3.38, 95%CI = 0.002). Conclussion: The present systematic review and meta-analysis supports that the loss of expression of the tumor suppressor pRb, assessed through immunohistochemistry, is a predictor of the malignant transformation risk of oral leukoplakias. Future studies are needed in other OPMDs following the recommendations provided based on current evidence gaps. Full article
(This article belongs to the Special Issue Oral Potentially Malignant Disorders and Oral Cavity Cancer)
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