Malignant and Potentially Malignant Disorders of the Oral Cavity: Updates from Pathogenesis to Therapy 2.0

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 11437

Special Issue Editors


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Guest Editor
Department of Health Sciences, University of Piemonte Orientale “UPO”, Vercelli, Italy
Interests: biomaterials; dental materials; tissue regeneration; tissue engineering; oral medicine; bacterial biofilm; anti-infective technologies
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Special Issue Information

Dear Colleagues,

This Special Issue, “Malignant and Potentially Malignant Disorders of the Oral Cavity: Updates from Pathogenesis to Therapy”, will focus on the pathophysiology, diagnosis, prognosis, and therapy of malignant and potentially malignant disorders of the oral cavity, but will not be limited to only these aspects.

This Special Issue is open to both clinical and pre-clinical research using multi-disciplinary approaches and is open to both original articles and reviews.

Oral squamous cell carcinoma (OSCC) represents the most frequent malignant tumor of the oral cavity, with an estimated annual incidence of 529,000 new cases (including cases in the oral cavity and pharynx) and more than 300,000 deaths. Recent trends highlight an increasing incidence in young women. Alcohol and smoking habits are still the main risk factors, although the role of Human Papilloma Virus has recently been debated. At advanced stages, the five-year survival is about 50%, so prevention is strongly recommended. New trends in therapy at advanced stages, such as immunotherapy, have also been introduced in the last few years.

Often, OSCC derives from oral potentially malignant disorders (OPMD), including mucosal lesions, which have a greater chance of transforming into cancer, e.g., oral leukoplakia, oral erythroplakia, palatal lesions in reverse smokers, oral lichen planus, oral submucous fibrosis, actinic keratosis, and discoid lupus erythematosus. No reliable prognostic factor nor treatment is currently available to avoid their risk of malignant transformation, and the need to clarify the “field cancerization” process is urgent.

Oral conditions and their associations with other systemic malignant and chronic inflammatory diseases will be considered as well.

Dr. Elena Varoni
Dr. Lia Rimondini
Guest Editors

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Keywords

  • oral squamous cell carcinoma
  • leukoplakia
  • erythroplakia
  • immunotherapy
  • smoking
  • human papilloma virus
  • field cancerization
  • oral microbiome

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Published Papers (5 papers)

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Research

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14 pages, 4145 KiB  
Article
Clinicopathological Significance of Cancer Stem Cell Markers (OCT-3/4 and SOX-2) in Oral Submucous Fibrosis and Oral Squamous Cell Carcinoma
by Divyambika Catakapatri Venugopal, Cynthia Leslie Caleb, Nandhini Priyadarshini Kirupakaran, Vidyarani Shyamsundar, Soundharya Ravindran, Madhavan Yasasve, Arvind Krishnamurthy, Thamizhchelvan Harikrishnan, Sathasivasubramanian Sankarapandian and Vijayalakshmi Ramshankar
Biomedicines 2023, 11(4), 1040; https://doi.org/10.3390/biomedicines11041040 - 28 Mar 2023
Cited by 2 | Viewed by 1759
Abstract
Oral submucous fibrosis (OSMF) is highly prevalent in South East Asia with higher rates of malignant transformation in Indian subcontinent. Numerous biomarkers are now being studied to predict disease prognosis and detect malignant alterations at an early stage. Patients with clinically and biopsy-proven [...] Read more.
Oral submucous fibrosis (OSMF) is highly prevalent in South East Asia with higher rates of malignant transformation in Indian subcontinent. Numerous biomarkers are now being studied to predict disease prognosis and detect malignant alterations at an early stage. Patients with clinically and biopsy-proven oral submucous fibrosis and oral squamous cell carcinoma were included in the study as the experimental group, while patients without a tobacco or betel nut habit who had their third molars surgically removed were included as the healthy control group. For the immunohistochemistry (IHC) investigation, 5-μm slices from formalin-fixed, paraffin-embedded tissue blocks (FFPE) were obtained. Fresh tissues (n = 45) from all three groups were collected and gene expression was studied using relative quantitation-based qPCR. The protein expression of octamer-binding transcription factor 3/4 (OCT 3/4) and sex-determining region Y-box 2 (SOX 2) was evaluated in the experimental group and compared with healthy controls. The IHC results showed a significant correlation with the expression of OCT 3/4 (p value = 0.000; χ2 = 20.244) and SOX 2 (p value = 0.006; χ2 = 10.101) among OSCC and OSMF patients in comparison to healthy controls. Both OCT 3/4 and SOX 2 showed overexpression of four-fold and three-fold in OSMF when compared to OSCC and healthy controls, respectively. This study shows the significant importance of cancer stem cell markers OCT 3/4 and SOX 2 to assess the disease prognosis in OSMF. Full article
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16 pages, 2864 KiB  
Article
Growth Conditions Influence Lactobacillus Cell-Free Supernatant Impact on Viability, Biofilm Formation, and Co-Aggregation of the Oral Periodontopathogens Fusobacterium nucleatum and Porphyromonas gingivalis
by Paola Zanetta, Diletta Francesca Squarzanti, Alessia di Coste, Angela Amoruso, Marco Pane and Barbara Azzimonti
Biomedicines 2023, 11(3), 859; https://doi.org/10.3390/biomedicines11030859 - 11 Mar 2023
Cited by 2 | Viewed by 1757
Abstract
Fusobacterium nucleatum and Porphyromonas gingivalis human periodontopathogens play a leading part in oral squamous cell carcinoma through cell proliferation, invasion, and persistent inflammation promotion and maintenance. To explore how the activity of Lactobacillus-derived cell-free supernatants (CFSs) can be influenced by growth medium [...] Read more.
Fusobacterium nucleatum and Porphyromonas gingivalis human periodontopathogens play a leading part in oral squamous cell carcinoma through cell proliferation, invasion, and persistent inflammation promotion and maintenance. To explore how the activity of Lactobacillus-derived cell-free supernatants (CFSs) can be influenced by growth medium components, CFSs were produced both in the standard MRS and the novel animal-derivative-free “Terreno Industriale Lattobacilli” (TIL) media, and in vitro screened for the containment of F. nucleatum and P. gingivalis both single and co-cultured and also for the interference on their co-aggregation. The viability assay demonstrated that the Limosilactobacillus reuteri LRE11 and Ligilactobacillus salivarius LS03 MRS-produced CFSs were significantly more effective against single and co-cultured pathogens. All the other CFSs significantly improved their efficacy when produced in TIL. Both MRS- and TIL-produced CFSs significantly inhibited the single and co-cultured pathogen biofilm formation. Only Levilactobacillus brevis LBR01 CFS in MRS specifically reduced F. nucleatum and P. gingivalis co-aggregation, while viable LBR01, LS03, and LRE11 in MRS significantly co-aggregated with the pathogens, but only LS03 cultivated in TIL improved this effect. This work paves the way to better consider environmental growth conditions when screening for probiotic and postbiotic efficacy as crucial to pathogen aggregation, adhesion to the host’s niches, and exclusion. Full article
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13 pages, 4032 KiB  
Article
Arsenic Trioxide Triggers Apoptosis of Metastatic Oral Squamous Cells Carcinoma with Concomitant Downregulation of GLI1 in Hedgehog Signaling
by Raphael Luís Rocha Nogueira, Taís Bacelar Sacramento de Araújo, Ludmila Faro Valverde, Viviane Aline Oliveira Silva, Bruno Raphael Ribeiro Cavalcante, Erik Aranha Rossi, Kyan James Allahdadi, Mitermayer Galvão dos Reis, Thiago Almeida Pereira, Ricardo D. Coletta, Daniel Pereira Bezerra, Bruno Solano de Freitas Souza, Rosane Borges Dias and Clarissa A. Gurgel Rocha
Biomedicines 2022, 10(12), 3293; https://doi.org/10.3390/biomedicines10123293 - 19 Dec 2022
Cited by 2 | Viewed by 1822
Abstract
Given the lack of advances in Oral Squamous Cell Carcinoma (OSCC) therapy in recent years, pharmacological strategies to block OSCC-related signaling pathways have gained prominence. The present study aimed to evaluate the therapeutic potential of Arsenic Trioxide (ATO) concerning its antitumoral effects and [...] Read more.
Given the lack of advances in Oral Squamous Cell Carcinoma (OSCC) therapy in recent years, pharmacological strategies to block OSCC-related signaling pathways have gained prominence. The present study aimed to evaluate the therapeutic potential of Arsenic Trioxide (ATO) concerning its antitumoral effects and the inhibition of the Hedgehog (HH) pathway in OSCC. Initially, ATO cytotoxicity was assessed in a panel of cell lines. Cell viability, cell cycle, death patterns, and cell morphology were analyzed, as well as the effect of ATO on the expression of HH pathway components. After the cytotoxic assay, HSC3 cells were chosen for all in vitro assays. ATO increased apoptotic cell death and nuclear fragmentation in the sub-G1 cell cycle phase and promoted changes in cell morphology. In addition, the reduced expression of GLI1 indicated that ATO inhibits HH activity. The present study provides evidence of ATO as an effective cytotoxic drug for oral cancer treatment in vitro. Full article
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Review

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18 pages, 2424 KiB  
Review
Oral Surgery and Osteoradionecrosis in Patients Undergoing Head and Neck Radiation Therapy: An Update of the Current Literature
by Giulia Corrao, Giovanni Carlo Mazzola, Niccolò Lombardi, Giulia Marvaso, Alberto Pispero, Elisa Baruzzi, Sem Decani, Marco Tarozzi, Luca Bergamaschi, Chiara Lorubbio, Ilaria Repetti, Anna Starzyńska, Daniela Alterio, Mohseen Ansarin, Roberto Orecchia, Fiorella D’Amore, Roberto Franchini, Andrea Nicali, Paolo Castellarin, Andrea Sardella, Giovanni Lodi, Elena Maria Varoni and Barbara Alicja Jereczek-Fossaadd Show full author list remove Hide full author list
Biomedicines 2023, 11(12), 3339; https://doi.org/10.3390/biomedicines11123339 - 18 Dec 2023
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Abstract
Osteoradionecrosis (ORN) is a serious long-term complication of head and neck radiotherapy (RT), which is often triggered by dental extractions. It results from avascular aseptic necrosis due to irradiated bone damage. ORN is challenging to treat and can lead to severe complications. Furthermore, [...] Read more.
Osteoradionecrosis (ORN) is a serious long-term complication of head and neck radiotherapy (RT), which is often triggered by dental extractions. It results from avascular aseptic necrosis due to irradiated bone damage. ORN is challenging to treat and can lead to severe complications. Furthermore, ORN causes pain and distress, significantly reducing the patient’s quality of life. There is currently no established preventive strategy. This narrative review aims to provide an update for the clinicians on the risk of ORN associated with oral surgery in head and neck RT patients, with a focus on the timing suitable for the oral surgery and possible ORN preventive treatments. An electronic search of articles was performed by consulting the PubMed database. Intervention and observational studies were included. A multidisciplinary approach to the patient is highly recommended to mitigate the risk of RT complications. A dental visit before commencing RT is highly advised to minimize the need for future dental extractions after irradiation, and thus the risk of ORN. Post-RT preventive strategies, in case of dento-alveolar surgery, have been proposed and include antibiotics, hyperbaric oxygen (HBO), and the combined use of pentoxifylline and tocopherol (“PENTO protocol”), but currently there is a lack of established standards of care. Some limitations in the use of HBO involve the low availability of HBO facilities, its high costs, and specific clinical contraindications; the PENTO protocol, on the other hand, although promising, lacks clinical trials to support its efficacy. Due to the enduring risk of ORN, removable prostheses are preferable to dental implants in these patients, as there is no consensus on the appropriate timing for their safe placement. Overall, established standards of care and high-quality evidence are lacking concerning both preventive strategies for ORN as well as the timing of the dental surgery. There is an urgent need to improve research for more efficacious clinical decision making. Full article
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12 pages, 279 KiB  
Review
Oral Cavity Squamous Cell Carcinoma: An Update of the Pharmacological Treatment
by Martina Imbesi Bellantoni, Giacomo Picciolo, Igor Pirrotta, Natasha Irrera, Mario Vaccaro, Federico Vaccaro, Francesco Squadrito and Giovanni Pallio
Biomedicines 2023, 11(4), 1112; https://doi.org/10.3390/biomedicines11041112 - 07 Apr 2023
Cited by 6 | Viewed by 3910
Abstract
Oral cavity squamous cell carcinoma (OCSCC) represents a serious health and socio-economic problem in different geographical areas of the world. It is characterized by a high rate of mortality, recurrence and metastasis. Despite the therapeutic strategies implemented for its management and resolution, currently [...] Read more.
Oral cavity squamous cell carcinoma (OCSCC) represents a serious health and socio-economic problem in different geographical areas of the world. It is characterized by a high rate of mortality, recurrence and metastasis. Despite the therapeutic strategies implemented for its management and resolution, currently the survival estimate for locally advanced disease is about 50%. The available therapeutic options comprise surgery and pharmacological treatment. Recently, an increased emphasis has been placed on the drugs that might be of benefit in this life-threatening disease. Therefore, the aim of this present review was to offer a general survey of the current available pharmacological treatment for OCSCC. The PubMed database was used to retrieve the papers using “OCSCC” as the search terms. We limited our search to the last 5 years to give a more updated and recent picture of the state of the art, including preclinical and clinical investigations. We found that 77 out of 201 papers were on the surgical treatment of OCSCC, 43 out of 201 focused on the radiotherapy and 81 out of 201 underwent evaluation for the aim of our review. We excluded the case reports, editorial letters, observational studies and papers written in languages other than English. A total of 12 articles were included in the final review. Our results showed that nanotechnologies use to enhance the efficacy of anticancer drugs such as: cisplatin, paclitaxel, cetuximab, EGFR antagonists, MEK1/2 and immune check inhibitors combination could have promising anti-cancer activity. However, the paucity of available data on drugs suggests the urgent need to improve the pharmacological armamentarium for OCSCC treatment. Full article
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