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16 pages, 4604 KiB

Open AccessArticle

EMT Dynamics in Lymph Node Metastasis of Oral Squamous Cell Carcinoma

by Yasmine Ghantous, Shiraz Mozalbat, Aysar Nashef, Murad Abdol-Elraziq, Shiran Sudri, Shareef Araidy, Hagar Tadmor and Imad Abu El-naaj

Cancers 2024, 16(6), 1185; https://doi.org/10.3390/cancers16061185 - 18 Mar 2024

Viewed by 814

Abstract

Background: Epithelial–mesenchymal transition (EMT) enables tumor cell invasion and metastasis. Many studies have demonstrated the critical role of EMT in lymph node metastasis in oral squamous cell carcinoma (OSCC). During EMT, epithelial cancer cells lose intercellular adhesion and apical–basal polarity and acquire mesenchymal [...] Read more.

Background: Epithelial–mesenchymal transition (EMT) enables tumor cell invasion and metastasis. Many studies have demonstrated the critical role of EMT in lymph node metastasis in oral squamous cell carcinoma (OSCC). During EMT, epithelial cancer cells lose intercellular adhesion and apical–basal polarity and acquire mesenchymal properties such as motility and invasiveness. A significant feature of EMT is cadherin switching, involving the downregulation of E-cadherin and upregulation of N-cadherin. The TGF-β/SMAD pathway can also induce EMT. We aimed to evaluate EMT markers as predictors of lymph node metastasis in OSCC. Methods: We performed genetic profiling of 159 primary OSCCs from TCGA and analyzed the expression of EMT markers, including cadherin switch genes (CDH1, CDH2), and TGF-β/SMAD pathway genes. Samples were divided into advanced (stage III–IV) and early (stage I–II) stage groups. Differential expression analysis was performed, as well as an independent validation study containing fresh OSCC samples. Results: TGF-β/SMAD pathway genes such as SMAD6 were upregulated in advanced stage tumors. N-cadherin and SNAIL2 were overexpressed in node-positive tumors. Keratins were downregulated in these groups. Conclusion: Our findings demonstrate that EMT marker expression correlates with lymph node metastasis in OSCC. Developing therapies targeting regulators such as N-cadherin may prevent metastasis and improve outcomes. Full article

(This article belongs to the Special Issue Oral Cancer: Prevention and Early Detection)

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16 pages, 2003 KiB

Open AccessArticle

Serum Anti-Zta and Anti-LMP1 Antibodies in Oropharyngeal Cancer Related to Epstein–Barr Virus—Diagnostic Usefulness

by Anna Polz, Kamal Morshed, Bartłomiej Drop, Andrzej Drop and Małgorzata Polz-Dacewicz

Cancers 2024, 16(2), 341; https://doi.org/10.3390/cancers16020341 - 13 Jan 2024

Cited by 1 | Viewed by 757

Abstract

Background: The role of the Epstein–Barr virus (EBV), the first known human oncogenic virus, in the development of nasopharyngeal cancer (NPC) is already well documented. There are few studies in the available scientific literature on oropharyngeal cancer associated with EBV infection. Due to [...] Read more.

Background: The role of the Epstein–Barr virus (EBV), the first known human oncogenic virus, in the development of nasopharyngeal cancer (NPC) is already well documented. There are few studies in the available scientific literature on oropharyngeal cancer associated with EBV infection. Due to the lack of an effective vaccine against EBV, it is necessary to search for new markers for the early diagnosis and prognosis of this disease. The aim of current study was to determine the usefulness of anti-Zta and anti-LMP1 antibodies as diagnostic and prognostic markers in EBV positive OPSCC patients. Methods: For this purpose, experiments were carried out to determine both the prevalence and level of EBVCA, EBNA1, EA, Zta, and LMP1 antibodies in serum patients depending on histological differentiation-grading and TNM classification (ELISA assay). Results: Based on the obtained results, we showed that OPSCC EBV positive patients are characterized by a higher level of anti-Zta antibodies than in the EBV negative group. Their level depended on the clinical stage. Moreover, a ROC analysis confirmed the diagnostic accuracy of anti-Zta antibodies. Conclusions: Anti-Zta and anti-LMP1 antibodies may be useful in the diagnosis of OPSCC. It seems that combined antibody testing should be performed to increase diagnostic accuracy. Full article

(This article belongs to the Special Issue Oral Cancer: Prevention and Early Detection)

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12 pages, 1777 KiB

Open AccessArticle

A Preliminary Study on Early Detection of Oral Cancer with Opportunistic Screening: Insights from Dental Surgeons in Sri Lanka

by Dewasundara Wijenarayana Vishwa Nimanthi Dissanayaka, Konara Mudiyanselage Shashika Lakmali Wijeratne, Kodituwakku Arachchige Don Kaushal Devin Amarasinghe, Ruwan Duminda Jayasinghe, Primali Rukmal Jayasooriya, Balapuwaduge Ranjit Rigobert Nihal Mendis and Tommaso Lombardi

Cancers 2023, 15(23), 5511; https://doi.org/10.3390/cancers15235511 - 22 Nov 2023

Cited by 1 | Viewed by 724

Abstract

In Sri Lanka, opportunistic screening is encouraged as a cost-effective tool to bring down the prevalence of oral cancer, which is the most common cancer among males. The objectives of the study were to determine the practices, attitudes, and level of competency of [...] Read more.

In Sri Lanka, opportunistic screening is encouraged as a cost-effective tool to bring down the prevalence of oral cancer, which is the most common cancer among males. The objectives of the study were to determine the practices, attitudes, and level of competency of dental surgeons regarding the early detection of oral cancer and oral potentially malignant disorders (OPMDs) through opportunistic screening. A prospective study was conducted online via a Google form using a pretested, self-administered questionnaire of 22 close-ended questions and 3 open-ended questions. Out of the 137 dental surgeons who responded, 88% (121/137) of the participants believed that screening high-risk target groups would be more effective in the early detection of oral cancer rather than opportunistic screening. Only 64% (88/137) of the participants frequently check for oral cancer and OPMDs when patients visit for dental treatment. Participants recalled an average of 34 patients (4628/137) with clinically suspicious lesions being diagnosed during examination at general dental practice during the past year, and 98% (134/137) of the participants believed that they should receive additional training in order to identify and diagnose clinically suspicious oral OPMDs and oral cancer. Opportunistic screening in general dental practice as an oral-cancer prevention strategy is appreciable, but due emphasis should be given to other prevention strategies such as population screening and screening high-risk target groups. The level of confidence of general dental practitioners in the early detection of oral cancer has to be raised in order to achieve higher standards in oral cancer prevention through opportunistic screening. Full article

(This article belongs to the Special Issue Oral Cancer: Prevention and Early Detection)

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11 pages, 601 KiB

Open AccessArticle

Screening for High-Risk Oral Human Papillomavirus (HPV31, HPV33, HPV35) in a Multi-Racial Pediatric and Adult Clinic Patient Population

by Hunter Hinton, Spencer Coleman, J. R. Salem and Karl Kingsley

Cancers 2023, 15(18), 4501; https://doi.org/10.3390/cancers15184501 - 10 Sep 2023

Cited by 2 | Viewed by 1114

Abstract

Many human papillomavirus (HPV) strains induce cancer in the cervix and the oral cavity. Although high-risk strains including HPV16 and HPV18 are commonly known, additional high-risk strains including HPV31, HPV33, and HPV35 may also induce carcinogenesis, and much less is known about their [...] Read more.

Many human papillomavirus (HPV) strains induce cancer in the cervix and the oral cavity. Although high-risk strains including HPV16 and HPV18 are commonly known, additional high-risk strains including HPV31, HPV33, and HPV35 may also induce carcinogenesis, and much less is known about their prevalence. Using an approved protocol, samples from a salivary biorepository were screened to find pediatric and adult samples from a multi-ethnic, university-based patient clinic population. A total of N = 86 samples from the saliva biorepository met the quality and concentration standards and were screened for high-risk HPV. qPCR screening of adult samples revealed n = 10/45 or 22% were HPV31- or HPV33-positive. In addition, a total of n = 9/41 or 21.9% of pediatric samples were either HPV31- or HPV33-positive (or both). No samples harbored HPV35. Most samples were derived from patients within the recommended vaccination or catch-up age range (age 9–45 years). These results demonstrated that a significant percentage of patients harbor additional high-risk HPV strains within the oral cavity, including HPV31 and HPV33. These data support oral healthcare provider recommendations for the newer nine-valent vaccine, which includes both HPV31 and HPV33. Full article

(This article belongs to the Special Issue Oral Cancer: Prevention and Early Detection)

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13 pages, 1553 KiB

Open AccessArticle

No Clear Clustering Dysbiosis from Salivary Microbiota Analysis by Long Sequencing Reads in Patients Affected by Oral Squamous Cell Carcinoma: A Single Center Study

by Rodolfo Mauceri, Martina Coppini, Davide Vacca, Giorgio Bertolazzi, Valeria Cancila, Claudio Tripodo and Giuseppina Campisi

Cancers 2023, 15(17), 4211; https://doi.org/10.3390/cancers15174211 - 22 Aug 2023

Cited by 1 | Viewed by 1149

Abstract

Background: Advancements in DNA sequencing technology have facilitated the assessment of the connection between the oral microbiome and various diseases. The aim of the present study was to investigate the salivary microbiota composition employing for the first time in the literature the Oxford [...] Read more.

Background: Advancements in DNA sequencing technology have facilitated the assessment of the connection between the oral microbiome and various diseases. The aim of the present study was to investigate the salivary microbiota composition employing for the first time in the literature the Oxford Nanopore Technology in patients affected by oral squamous cell carcinoma (OSCC). Methods: Unstimulated saliva samples of 31 patients were collected (24 OSCC patients and 7 controls). DNA was extracted using the QIAamp DNA Blood Kit and metagenomic long sequencing reads were performed using the MinION device. Results: In the OSCC group, 13 were males and 11 were females, with a mean age of 65.5 ± 13.9 years; in the control group, 5 were males and 2 were females, with a mean age of 51.4 ± 19.2 years. The border of the tongue was the most affected OSCC site. The microorganisms predominantly detected in OSCC patients were Prevotella, Chlamydia, Tissierellia, Calothrix, Leotiomycetes, Firmicutes and Zetaproteobacteria. Conclusions: This study confirmed the predominance of periodontopathic bacteria in the salivary microbiome in the OSCC group. If a direct correlation between oral dysbiosis and OSCC onset was proven, it could lead to new prevention strategies and early diagnostic tools. Full article

(This article belongs to the Special Issue Oral Cancer: Prevention and Early Detection)

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17 pages, 3193 KiB

Open AccessArticle

Identification of Neck Lymph Node Metastasis-Specific microRNA—Implication for Use in Monitoring or Prediction of Neck Lymph Node Metastasis

by Yutaro Higashi, Kodai Nakamura, Ryota Takaoka, Mika Tani, Yusaku Noma, Kazuki Mori, Kota Yamashiro, Seiya Yokoyama, Tomofumi Hamada and Tsuyoshi Sugiura

Cancers 2023, 15(15), 3769; https://doi.org/10.3390/cancers15153769 - 25 Jul 2023

Cited by 1 | Viewed by 875

Abstract

MicroRNAs (miRNAs) have attracted attention as non-invasive cancer biomarkers in various cancers; however, they have not been adequately investigated in oral squamous cell carcinoma (OSCC). This study investigated the diagnostic performance of serum-derived miRNAs at initial diagnosis for primary neck lymph node metastasis [...] Read more.

MicroRNAs (miRNAs) have attracted attention as non-invasive cancer biomarkers in various cancers; however, they have not been adequately investigated in oral squamous cell carcinoma (OSCC). This study investigated the diagnostic performance of serum-derived miRNAs at initial diagnosis for primary neck lymph node metastasis and the predictive performance for late neck lymph node metastasis based on long-term (up to approximately 8 years) follow-up of patients with OSCC. The expression of miRNAs in 40 patients with OSCC was quantified using real-time PCR (qPCR), and a comprehensive statistical analysis of the correlation of miRNA expression for primary and late neck lymph node metastases was performed. For the diagnosis of primary neck lymph node metastases, miR-423 and miR-125 were accurate. The miRNA index for primary metastasis diagnosis (miR-PM) calculated by regression analysis showed high diagnostic accuracy. The miR-5100 was useful for predicting late neck lymph node metastases. The miRNA index for late metastasis prediction (miR-LM) calculated using regression analysis showed high prediction accuracy. MiRNAs were useful for diagnosing primary neck lymph node metastases in OSCC and predicting late neck lymph node metastases. It may help to consider individualized treatment, including follow-up, surgical methods, and postoperative management. Full article

(This article belongs to the Special Issue Oral Cancer: Prevention and Early Detection)

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14 pages, 615 KiB

Open AccessArticle

Risk of Oral Squamous Cell Carcinoma in One Hundred Patients with Oral Lichen Planus: A Follow-Up Study of Umberto I University Hospital of Rome

by Gianluca Tenore, Ahmed Mohsen, Federica Rocchetti, Giulia Rossi, Andrea Cassoni, Andrea Battisti, Marco Della Monaca, Cira Rosaria Tiziana Di Gioia, Francesca De Felice, Andrea Botticelli, Valentino Valentini, Carlo Della Rocca, Marco De Vincentiis, Antonella Polimeni and Umberto Romeo

Cancers 2023, 15(11), 3004; https://doi.org/10.3390/cancers15113004 - 31 May 2023

Cited by 6 | Viewed by 1416

Abstract

This study aims to retrospectively assess the potential risk of malignant transformation in patients with diagnosed oral lichen planus (OLP) between 2015 and 2022, and to evaluate the influence of different risk factors. The department’s database and medical records from 2015 to 2022 [...] Read more.

This study aims to retrospectively assess the potential risk of malignant transformation in patients with diagnosed oral lichen planus (OLP) between 2015 and 2022, and to evaluate the influence of different risk factors. The department’s database and medical records from 2015 to 2022 were searched for patients with a confirmed diagnosis of OLP based on both clinical and histological parameters. A total of 100 patients (59 females and 41 males) were found with a mean age of 64.03 years. In the considered period, the percentage of diagnosed OLP patients was 1.6%, while the percentage of diagnosed OLP patients with transformation to oral squamous cell carcinoma (OSCC) was 0.18%. A statistically significant difference was found with age (p = 0.038), tobacco status (p = 0.022), and radiotherapy (p = 0.041). The analysis revealed the presence of significant risk in ex-smokers (>20 pack-years), with an odds ratio (OR) of 10.0000 (95% confidence interval (95% CI) 1.5793–63.3186); in alcohol-drinker patients, with an OR of 4.0519 (95% CI 1.0182–16.1253); in ex-smoker and alcohol-drinker patients, with OR of 17.6250 (95% CI 2.2464–138.2808); and in patients who had undergone radiotherapy, with OR of 6.3000 (95% CI 1.2661–31.3484). The malignant transformation of oral lichen planus was slightly higher than thought, and the results revealed a possible association with age, tobacco and alcohol status, and history of radiotherapy. An elevated risk of malignant transformation was observed in heavy ex-smoker patients, alcohol-drinker patients, and alcohol-drinker patients with a history of smoking (ex-smokers). Persuading the patient to quit tobacco and alcohol consumption and periodic follow-ups are recommended in general, but particularly in the presence of these risk factors. Full article

(This article belongs to the Special Issue Oral Cancer: Prevention and Early Detection)

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10 pages, 256 KiB

Open AccessReview

Precursor Lesions, Overdiagnosis, and Oral Cancer: A Critical Review

by Nicola Cirillo

Cancers 2024, 16(8), 1550; https://doi.org/10.3390/cancers16081550 - 18 Apr 2024

Viewed by 423

Abstract

Despite the profession placing great emphasis on oral potentially malignant disorders (OPMDs) as a gateway for early recognition and consequently better outcomes for oral cancer, the death rates for lip and oral cavity cancer have remained stagnant for three decades. Evidence shows that [...] Read more.

Despite the profession placing great emphasis on oral potentially malignant disorders (OPMDs) as a gateway for early recognition and consequently better outcomes for oral cancer, the death rates for lip and oral cavity cancer have remained stagnant for three decades. Evidence shows that only a small fraction of oral cancers are in fact preceded by OPMDs, and that most OPMDs have an annual transformation rate of less than 1%. As OPMDs encompass a very heterogeneous group of oral conditions, it could be argued that only patients with oral mucosal diseases bearing a substantial risk of malignant transformation warrant close surveillance and treatment, these include proliferative leukoplakia, erythroplakia, non-homogeneous leukoplakia, as well as diseases presenting with severe dysplasia at biopsy. In this narrative review, I discuss the intricate epidemiology of the malignancies that we colloquially refer to as oral cancer, explore the limitations of focusing on OPMDs to reduce the incidence and mortality of oral cavity cancer, and argue that a may-be cancer label represents overdiagnosis for most OPMDs. Full article

(This article belongs to the Special Issue Oral Cancer: Prevention and Early Detection)

16 pages, 702 KiB

Open AccessReview

Bisphosphonates and Their Connection to Dental Procedures: Exploring Bisphosphonate-Related Osteonecrosis of the Jaws

by Emily Sunny Lee, Meng-Chen Tsai, Jing-Xuan Lee, Chuki Wong, You-Ning Cheng, An-Chi Liu, You-Fang Liang, Chih-Yuan Fang, Chia-Yu Wu and I-Ta Lee

Cancers 2023, 15(22), 5366; https://doi.org/10.3390/cancers15225366 - 10 Nov 2023

Viewed by 1835

Abstract

Bisphosphonates are widely used to treat osteoporosis and malignant tumors due to their effectiveness in increasing bone density and inhibiting bone resorption. However, their association with bisphosphonate-related osteonecrosis of the jaws (BRONJ) following invasive dental procedures poses a significant challenge. This review explores [...] Read more.

Bisphosphonates are widely used to treat osteoporosis and malignant tumors due to their effectiveness in increasing bone density and inhibiting bone resorption. However, their association with bisphosphonate-related osteonecrosis of the jaws (BRONJ) following invasive dental procedures poses a significant challenge. This review explores the functions, mechanisms, and side effects of bisphosphonates, emphasizing their impact on dental procedures. Dental patients receiving bisphosphonate treatment are at higher risk of BRONJ, necessitating dentists’ awareness of these risks. Topical bisphosphonate applications enhance dental implant success, by promoting osseointegration and preventing osteoclast apoptosis, and is effective in periodontal treatment. Yet, systemic administration (intravenous or intraoral) significantly increases the risk of BRONJ following dental procedures, particularly in inflamed conditions. Prevention and management of BRONJ involve maintaining oral health, considering alternative treatments, and careful pre-operative and post-operative follow-ups. Future research could focus on finding bisphosphonate alternatives with fewer side effects or developing combinations that reduce BRONJ risk. This review underscores the need for further exploration of bisphosphonates and their implications in dental procedures. Full article

(This article belongs to the Special Issue Oral Cancer: Prevention and Early Detection)

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13 pages, 694 KiB

Open AccessReview

Exploring Possible Diagnostic Precancerous Biomarkers for Oral Submucous Fibrosis: A Narrative Review

by Jie-Ru You, Ya-Ting Chen, Chia-Yu Hsieh, Sin-Yu Chen, Tzu-Yao Lin, Jing-Syuan Shih, Guan-Ting Chen, Sheng-Wei Feng, Tzu-Yu Peng, Chia-Yu Wu and I-Ta Lee

Cancers 2023, 15(19), 4812; https://doi.org/10.3390/cancers15194812 - 30 Sep 2023

Cited by 2 | Viewed by 1056

Abstract

Oral submucous fibrosis (OSF) stands as a progressive oral ailment, designated as a potentially malignant disorder. OSF has gained widespread recognition as a significant precursor to malignant transformation. In the pursuit of dependable, straightforward, and non-invasive diagnostic measures for the early detection of [...] Read more.

Oral submucous fibrosis (OSF) stands as a progressive oral ailment, designated as a potentially malignant disorder. OSF has gained widespread recognition as a significant precursor to malignant transformation. In the pursuit of dependable, straightforward, and non-invasive diagnostic measures for the early detection of oral malignant progression, research has delved into potential diagnostic biomarkers of OSF. This comprehensive review delves into current investigations that explore the correlation between various biomarkers and OSF. The molecular biomarkers of OSF are categorized based on cytology and sampling methods. Moreover, this review encompasses pertinent studies detailing how these biomarkers are acquired and processed. Within this scope, we scrutinize four potential biomarkers that hold the promise of facilitating the development of diagnostic tools for detecting early-stage OSF. Full article

(This article belongs to the Special Issue Oral Cancer: Prevention and Early Detection)

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