Special Issue "Malignant and Potentially Malignant Disorders of the Oral Cavity: Updates from Pathogenesis to Therapy"

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

Deadline for manuscript submissions: closed (31 December 2020).

Special Issue Editors

Prof. Dr. Lia Rimondini
E-Mail Website
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-iinfective technologies
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Elena Maria Varoni
E-Mail Website
Guest Editor

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 pathophysiology, diagnosis, prognosis and therapy of malignant and potentially malignant disorders of the oral cavity, but not limited to only these aspects.

It is open to both clinical and pre-clinical research, in a multi-disciplinary approach, and covers 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 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 been recently debated. At advanced stages, the five-year survival is about 50%, so prevention is strongly recommended. New trends in therapy of advanced stages have been also introduced in the last few years, including immunotherapy.

Often, OSCC derives from oral potentially malignant disorders (OPMD), which include those mucosal lesions with greater chance to transform in cancer, e.g., oral leukoplakia, oral erythroplakia, palatal lesions in reverse smokers, oral lichen planus, oral submucous fibrosis, actinic keratosis, and discoid lupus erythematous. No reliable prognostic factor nor treatment is currently available to avoid their risk of malignant transformation, and the need for clarifying the process of “field cancerization” is still demanding.

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

Prof. Dr. Lia Rimondini
Dr. Elena Maria Varoni
Guest Editors

Manuscript Submission Information

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Keywords

  • oral squamous cell carcinoma
  • leukoplakia
  • erythroplakia
  • immunotherapy
  • smoking
  • Human Papilloma Virus
  • field cancerization
  • oral microbiome

Published Papers (10 papers)

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Research

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Article
Disorders of Dental Hard Tissues Induced by Radioiodine-131 (I-131) Therapy Used in Differentiated Thyroid Cancer: An In Vitro Study
Biomedicines 2020, 8(11), 475; https://doi.org/10.3390/biomedicines8110475 - 05 Nov 2020
Cited by 1 | Viewed by 722
Abstract
This study aimed to evaluate, in vitro, the effects of I-131 on enamel and dentin in healthy human incisive permanent maxillary teeth. Our in vitro model analogue with the in vivo conditions of differentiated thyroid carcinoma patients treated with I-131, consisted in a [...] Read more.
This study aimed to evaluate, in vitro, the effects of I-131 on enamel and dentin in healthy human incisive permanent maxillary teeth. Our in vitro model analogue with the in vivo conditions of differentiated thyroid carcinoma patients treated with I-131, consisted in a solution of I-131 dissolved in artificial saliva. A total of 48 teeth were divided into eight groups (n = 6): control, irradiation groups at 3, 6, 12, 24, 36, 48, and 192 h, respectively. At the end of radiation exposure, radioiodine activity of specimens was assessed. Fine microstructure, nanostructure, surface roughness, and hidroxyapatite (HAP) crystallite diameter were investigated by atomic force microscopy (AFM) to both enamel and dentin structures. There is a constant increase of radioactivity in dental structures at 3, 6, 12, 24 h, due to progressive retention and I-131 migration, with a maximum at 36 h. Enamel showed notable alterations, which was correlated with the increase of the treatment time. A relevant visible distance between the HAP prisms was observed after 24 h. The surface suffered a loss in its compact structure. I-131 acts in the same way on HAP crystallites in dentin as in those in enamel. It was noticed that their morpho-dimensional changes occurred only after 12 h of treatment. Radioiodine-131 determines degradation of enamel and dentin by starting from the alteration of the crystalline network of HAP prisms, transforming them from compact materials into an agglomeration of rocky submicron structures. Full article
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Article
Glutathione-Stabilized Silver Nanoparticles: Antibacterial Activity against Periodontal Bacteria, and Cytotoxicity and Inflammatory Response in Oral Cells
Biomedicines 2020, 8(10), 375; https://doi.org/10.3390/biomedicines8100375 - 23 Sep 2020
Cited by 3 | Viewed by 1183
Abstract
Silver nanoparticles (AgNPs) have been proposed as new alternatives to limit bacterial dental plaque because of their antimicrobial activity. Novel glutathione-stabilized silver nanoparticles (GSH-AgNPs) have proven powerful antibacterial properties in food manufacturing processes. Therefore, this study aimed to evaluate the potentiality of GSH-AgNPs [...] Read more.
Silver nanoparticles (AgNPs) have been proposed as new alternatives to limit bacterial dental plaque because of their antimicrobial activity. Novel glutathione-stabilized silver nanoparticles (GSH-AgNPs) have proven powerful antibacterial properties in food manufacturing processes. Therefore, this study aimed to evaluate the potentiality of GSH-AgNPs for the prevention/treatment of oral infectious diseases. First, the antimicrobial activity of GSH-AgNPs against three oral pathogens (Porphyromonas gingivalis, Fusobacterium nucleatum, and Streptococcus mutans) was evaluated. Results demonstrated the efficiency of GSH-AgNPs in inhibiting the growth of all bacteria, especially S. mutans (IC50 = 23.64 μg/mL, Ag concentration). Second, GSH-AgNPs were assayed for their cytotoxicity (i.e., cell viability) toward a human gingival fibroblast cell line (HGF-1), as an oral epithelial model. Results indicated no toxic effects of GSH-AgNPs at low concentrations (≤6.16 µg/mL, Ag concentration). Higher concentrations resulted in losing cell viability, which followed the Ag accumulation in cells. Finally, the inflammatory response in the HGF-1 cells after their exposure to GSH-AgNPs was measured as the production of immune markers (interleukins 6 and 8 (IL-6 and IL-8) and tumor necrosis factor-alpha (TNF-α)). GSH-AgNPs activates the inflammatory response in human gingival fibroblasts, increasing the production of cytokines. These findings provide new insights for the use of GSH-AgNPs in dental care and encourage further studies for their application. Full article
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Article
Chronic Periodontitis and Immunity, Towards the Implementation of a Personalized Medicine: A Translational Research on Gene Single Nucleotide Polymorphisms (SNPs) Linked to Chronic Oral Dysbiosis in 96 Caucasian Patients
Biomedicines 2020, 8(5), 115; https://doi.org/10.3390/biomedicines8050115 - 09 May 2020
Cited by 29 | Viewed by 1866
Abstract
Chronic periodontitis (CP) is a complex pathology with a significant impact worldwide causing bone loss. Oral dysbiosis is a highly inflammatory condition associated to a long-term insulting infection and represents an underestimated CP key factor associated with an imbalance of pro-inflammatory and anti-inflammatory [...] Read more.
Chronic periodontitis (CP) is a complex pathology with a significant impact worldwide causing bone loss. Oral dysbiosis is a highly inflammatory condition associated to a long-term insulting infection and represents an underestimated CP key factor associated with an imbalance of pro-inflammatory and anti-inflammatory gene responses. The presence of a single nucleotide polymorphisms (SNPs) in the promoter region of interleukin 10 (IL-10) gene −1082, −819, and −592 was a possible determinant cause. This translational research aimed to provide outcomes on the role of IL-10 gene expression in bone loss diseases in patients affected by CP. Caucasian patients (n = 96) affected by CP were recruited from the Italian population. The subgingival samples were collected using the Bacterial Periodontal Assessment by Biomolecular Diagnostic® and the characterization of a set of 15 bacterial DNA responsible of periodontitis was performed by real-time multiplex PCR. In addition, two viruses, Epstein–Barr Virus (EBV) and Herpes Simplex Virus 1 (HSV-1), and a pathogenic fungi (Candida albicans) were included as a part of our panel. Our results confirmed an existing association between IL-10 gene polymorphisms and polymorphism of tumor necrosis factor alpha (TNFα), interleukin 1α-β-RN (IL-1α-β-RN), collagen type-l alpha (COLIA1), and vitamin D receptor (VDRs) genes in CP. Further studies are needed to improve diagnosis and endorse more effective therapeutic procedures for periodontal disease. Full article
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Article
Does Medication-Related Osteonecrosis of the Jaw Influence the Quality of Life of Cancer Patients?
Biomedicines 2020, 8(4), 95; https://doi.org/10.3390/biomedicines8040095 - 24 Apr 2020
Cited by 9 | Viewed by 1080
Abstract
The aim of this study is to observe the influence of Medication-Related Osteonecrosis of the Jaw (MRONJ) on the physical and mental conditions of cancer patients using a Quality of Life (QoL) questionnaire during regular dental practice measures. Twenty cancer patients (8 males [...] Read more.
The aim of this study is to observe the influence of Medication-Related Osteonecrosis of the Jaw (MRONJ) on the physical and mental conditions of cancer patients using a Quality of Life (QoL) questionnaire during regular dental practice measures. Twenty cancer patients (8 males and 12 females) with established MRONJ were enrolled in the “MoMax” (Oral Medicine and Maxillofacial) project of the Department of Oral Sciences and Maxillofacial Surgery at “Sapienza” University of Rome, and were included in the study. The 12-item Short Form Survey was used to evaluate the QoL. Statistical analysis revealed a significant difference for Mental Component Summary (MCS) scores based on age (p = 0.018). The regression analysis revealed that the Physical Component Summary (PCS) scores were negatively influenced by the anti-resorptive medication duration (p = 0.031 and β = −1.137). No significant differences were observed with the other variables considered. The QoL of cancer patients is generally deteriorated and MRONJ may cause a further negative impact. This study highlights the possible need to include psychosocial and physical evaluations in the management process of MRONJ in cancer patients. Full article
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Article
The Lymphoscintigraphic Study of Unpredictable Head and Neck Cutaneous Melanoma Lymphatic Drainage
Biomedicines 2020, 8(4), 70; https://doi.org/10.3390/biomedicines8040070 - 27 Mar 2020
Cited by 1 | Viewed by 980
Abstract
Head and neck cutaneous melanoma (HNCM) does not always follow standard lymphatic drainage; typical expected lymphatic pathways are associated with unexpected ones. The aim of this study was to investigate the relation between the primary HNCM sites and all possible lymphatic drainage pathways [...] Read more.
Head and neck cutaneous melanoma (HNCM) does not always follow standard lymphatic drainage; typical expected lymphatic pathways are associated with unexpected ones. The aim of this study was to investigate the relation between the primary HNCM sites and all possible lymphatic drainage pathways by lymphoscintigraphy with a special focus on the unexpected sentinel lymph node (SLNs) detection. We retrospectively analyzed 67 patients (46 M, 21 F; mean age 63 years) who underwent lymphoscintigraphy from January 2004 to November 2018. 99mTc-serum albumin was injected intra-dermally at the dose of 18–37 MBq in 0.2–0.4 mL. All patients underwent dynamic and static image acquisition. For all patients, the relation between the expected and unexpected SLNs was performed using the “Sidney Melanoma Unit Database” as our reference. The relation was performed also according to the primary HNCM localization. Cohens’ kappa was calculated. In 61/67 (91%) of patients, SLNs were detected only in predictable sites, while in six/67 (9%), unexpected SLNs were revealed. In all patients, the agreement proportion was 91% (95% confidence interval CI 0.8–0.96) and Cohen’s K was 0.11 (95% CI 0–0.43). Regarding the primary melanoma sites, the nasolabial field HNCM showed the highest rate of concordance (K = 0.60; 95%, CI 0.32–0.89) while the preauricular region HNCM revealed the highest rate of discordance with the clinically predictable drainage. The HNCM lymphatic drainage is extremely variable in regard to both the sites and the number of involved SLNs. The lymphoscintigraphic study is highly recommended to identify all possible SLNs in order to perform an accurate staging for all patients and to avoid missing unexpected SLNs. Full article
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Article
Periodontitis Stage III–IV, Grade C and Correlated Factors: A Histomorphometric Study
Biomedicines 2019, 7(2), 43; https://doi.org/10.3390/biomedicines7020043 - 12 Jun 2019
Cited by 1 | Viewed by 1597
Abstract
Background: Periodontitis is a disease that leads to serious functional and esthetic dysfunctions. Periodontitis exists in different forms, and its etiology is related to multiple component causes. Two key processes involved in the evolution of this pathology are angiogenesis and inflammatory infiltrate. The [...] Read more.
Background: Periodontitis is a disease that leads to serious functional and esthetic dysfunctions. Periodontitis exists in different forms, and its etiology is related to multiple component causes. Two key processes involved in the evolution of this pathology are angiogenesis and inflammatory infiltrate. The aim of this study was to understand if important factors such as smoking, gender, age, plaque, pus, and probing pocket depth could influence the histomorphological pattern of generalized stage III–IV, grade C periodontitis (GPIII–IVC), which is a particular form of periodontitis. Methods: Eighteen subjects with GPIII–IVC were enrolled in this study. The percentage of inflammatory cells and the vascular area were measured and evaluated in relation to each periodontal disease-associated factor. Results: Females showed a significant increase in the percentage of inflammatory cells compared to males (6.29% vs. 2.28%, p-value = 0.020) and it was higher in non-smokers than in smokers (4.56% vs. 3.14%, p-value = 0.048). Young patients showed a significant increase in vascular area percentage compared to older patients (0.60% vs. 0.46%, p-value = 0.0006) and this percentage was also higher in non-smokers compared to smokers (0.41% vs. 0.55%, p-value = 0.0008). The vascular area was also more than halved in subjects with residual plaque on tooth surfaces (0.74% vs. 0.36%, p-value = 0.0005). Conclusions: These results suggested that even if these factors are commonly related to the worsening of periodontal status, some of them (pus and periodontal probing depth (PPD)) do not affect the inflammatory and vascular patterns. Full article
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Review

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Review
Oral and Psychological Alterations in Haemophiliac Patients
Biomedicines 2019, 7(2), 33; https://doi.org/10.3390/biomedicines7020033 - 20 Apr 2019
Cited by 25 | Viewed by 2039
Abstract
Haemophiliacs are hereditary coagulopathies whose basic anomaly consists of the quantitative or qualitative alteration of one or more plasma proteins in the coagulation system. The objective of this review is to analyse all risk factors, predispositions and alterations to the oral-maxillofacial district in [...] Read more.
Haemophiliacs are hereditary coagulopathies whose basic anomaly consists of the quantitative or qualitative alteration of one or more plasma proteins in the coagulation system. The objective of this review is to analyse all risk factors, predispositions and alterations to the oral-maxillofacial district in patients with haemophilia. The broader assessment also includes the psychological aspects that could affect the treatment and maintenance of oral conditions. The study takes into consideration all the works in the literature in the last 10 years. Works that present oral, dental and psychological changes in haemophilia patients have been combined. A total of 16 studies were analysed carefully evaluating and explaining all the alterations and risk factors that this disease provides. The aim of the review is to report all the anomalies reported in the literature for these patients, and to direct and update the clinician in the treatment of haemophilia patients. Full article
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Review
Oral Dysbiosis in Pancreatic Cancer and Liver Cirrhosis: A Review of the Literature
Biomedicines 2018, 6(4), 115; https://doi.org/10.3390/biomedicines6040115 - 11 Dec 2018
Cited by 38 | Viewed by 3011
Abstract
The human body is naturally colonized by a huge number of different commensal microbial species, in a relatively stable equilibrium. When this microbial community undergoes dysbiosis at any part of the body, it interacts with the innate immune system and results in a [...] Read more.
The human body is naturally colonized by a huge number of different commensal microbial species, in a relatively stable equilibrium. When this microbial community undergoes dysbiosis at any part of the body, it interacts with the innate immune system and results in a poor health status, locally or systemically. Research studies show that bacteria are capable of significantly influencing specific cells of the immune system, resulting in many diseases, including a neoplastic response. Amongst the multiple different types of diseases, pancreatic cancer and liver cirrhosis were significantly considered in this paper, as they are major fatal diseases. Recently, these two diseases were shown to be associated with increased or decreased numbers of certain oral bacterial species. These findings open the way for a broader perception and more specific investigative studies, to better understand the possible future treatment and prevention. This review aims to describe the correlation between oral dysbiosis and both pancreatic cancer and liver cirrhotic diseases, as well as demonstrating the possible diagnostic and treatment modalities, relying on the oral microbiota, itself, as prospective, simple, applicable non-invasive approaches to patients, by focusing on the state of the art. PubMed was electronically searched, using the following key words: “oral microbiota” and “pancreatic cancer” (PC), “liver cirrhosis”, “systemic involvement”, and “inflammatory mediators”. Oral dysbiosis is a common problem related to poor oral or systemic health conditions. Oral pathogens can disseminate to distant body organs via the local, oral blood circulation, or pass through the gastrointestinal tract and enter the systemic circulation. Once oral pathogens reach an organ, they modify the immune response and stimulate the release of the inflammatory mediators, this results in a disease. Recent studies have reported a correlation between oral dysbiosis and the increased risk of pancreatic and liver diseases and provided evidence of the presence of oral pathogens in diseased organs. The profound impact that microbial communities have on human health, provides a wide domain towards precisely investigating and clearly understanding the mechanism of many diseases, including cancer. Oral microbiota is an essential contributor to health status and imbalance in this community was correlated to oral and systemic diseases. The presence of elevated numbers of certain oral bacteria, particularly P. gingivalis, as well as elevated levels of blood serum antibodies, against this bacterial species, was associated with a higher risk of pancreatic cancer and liver cirrhosis incidence. Attempts are increasingly directed towards investigating the composition of oral microbiome as a simple diagnostic approach in multiple diseases, including pancreatic and liver pathosis. Moreover, treatment efforts are concerned in the recruitment of microbiota, for remedial purposes of the aforementioned and other different diseases. Further investigation is required to confirm and clarify the role of oral microbiota in enhancing pancreatic and liver diseases. Improving the treatment modalities requires an exertion of more effort, especially, concerning the microbiome engineering and oral microbiota transplantation. Full article

Other

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Case Report
Use of Platelet Rich Fibrin (PRF)-Based Autologous Membranes for Tooth Extraction in Patients under Bisphosphonate Therapy: A Case Report
Biomedicines 2019, 7(4), 89; https://doi.org/10.3390/biomedicines7040089 - 10 Nov 2019
Cited by 1 | Viewed by 1587
Abstract
Tooth extraction in patients treated with bisphosphonates (BPs) for osteoporosis or cancer exposes the patient to the risk of osteonecrosis of the jaw. An autologous membrane using platelet-rich fibrin (PRF) is an innovative technique to promote wound healing, which allows obtaining a hermetic [...] Read more.
Tooth extraction in patients treated with bisphosphonates (BPs) for osteoporosis or cancer exposes the patient to the risk of osteonecrosis of the jaw. An autologous membrane using platelet-rich fibrin (PRF) is an innovative technique to promote wound healing, which allows obtaining a hermetic closure of the post-extractive surgical site without the need of mucoperiosteal flaps or periosteal releasing incisions. Here, we report the case of a 70-year-old woman, in therapy with alendronate for 12 years, requiring the upper right premolar extraction because of a crown fracture. After the tooth extraction performed under antiseptic and antibiotic coverage, the PRF autologous membrane was placed on the surgical wound to close completely the post-extraction site. Follow-up visits were carried out after one, two, four weeks and two months from the intervention. The complete re-epithelization of the wound was observed without signs of infection. The use of PRF for the closure of post-extraction sockets in patients taking BPs appears to be a promising alternative to the more invasive surgical procedures. Future clinical trials will be pivotal in elucidating the effectiveness of PRF to prevent BP-related osteonecrosis after tooth extraction. Full article
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Case Report
Zimmermann-Laband-1 Syndrome: Clinical, Histological, and Proteomic Findings of a 3-Year-Old Patient with Hereditary Gingival Fibromatosis
Biomedicines 2019, 7(3), 48; https://doi.org/10.3390/biomedicines7030048 - 29 Jun 2019
Cited by 6 | Viewed by 1587
Abstract
Background: Zimmermann-Laband-1 syndrome (ZLS-1; OMIM# 135500) is a rare genetic disorder whose oral pathognomonic sign is the development of progressive, diffuse, and severe gingival hypertrophy. Most children with abnormally gingival hyperplasia may also present multiple unerupted teeth and skeletal deformities of maxillary arches [...] Read more.
Background: Zimmermann-Laband-1 syndrome (ZLS-1; OMIM# 135500) is a rare genetic disorder whose oral pathognomonic sign is the development of progressive, diffuse, and severe gingival hypertrophy. Most children with abnormally gingival hyperplasia may also present multiple unerupted teeth and skeletal deformities of maxillary arches (i.e., skeletal anterior open bite). Despite phenotypic variability of the clinical spectrum, gingival fibromatosis is the hallmark of ZLS-1. Method: In this study, we report a 3-year-old male patient with a ZLS-1-related gingival overgrowth and failure of eruption of the deciduous teeth in the molar area. Surgical excision was performed under general anesthesia. Results: At three weeks follow-up, esthetics was significantly improved in terms of gingival appearance, and teeth eruption allowed an adequate masticatory function. Conclusion: In severe cases, surgical removal of the hyperplasic fibrous tissue may be required to expose unerupted teeth and establish a proper gingival contour. Surgical excision under general anesthesia is an elective procedure for patients with special needs, mental disability, as well as young and adult patients with dental anxiety type II and IV associated with poor oral health. Full article
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