Has the 8th American joint committee on cancer TNM staging improved prognostic performance in oral cancer? A systematic review / ¿Ha mejorado la estadificación TNM del octavo comité conjunto estadounidense sobre cáncer? ¿Rendimiento pronóstico en el cáncer oral? Una revisión sistemática

Background: The 8th edition of the American Joint Committee on Cancer (AJCC) classification has introduced two new parameters: depth of invasion (DOI) and extranodal extension (ENE). The aim of this systematic review was to determine whether this 8th edition referred to oral squamous cell carcinoma (OSCC) offers performance superior to that of the 7th edition in relation to overall survival (OS) and disease-specific survival (DSS). Material and Methods: The review was carried out following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. The PubMed (MEDLINE), Scopus and Cochrane Library databases were searched covering the period up until April 7th, 2022.Results: Thirteen retrospective cohort studies were finally included. The introduction of DOI and ENE in the 8th edition of the AJCC classification resulted in improved prognostic performance of the classification. Conclusions: Patients with OSCC can be better classified in relation to OS and DSS, while maintaining the simplicity and ease of use of the classification. This allows more appropriate treatment protocols to be applied and affords a better estimation of the prognosis of each patient.(AU)

Malignant development of proliferative verrucous/multifocal leukoplakia: A critical systematic review, meta-analysis and proposal of diagnostic criteria.

BACKGROUND: Proliferative verrucous/multifocal leukoplakia (PVML) is an oral potentially malignant disorder (OPMD) that exhibits high rates of malignant development (MD). This study aimed to analyse the risk of MD of PVML, as well as to investigate the possible risk factors associated with its malignization. METHODS: A bibliographical search of the PubMed, Embase, Web of Science, and Scopus databases was conducted. PVML MD rates were calculated as a pooled proportion, and the risk factors were calculated as risk ratios, using fixed and random models based on the presence of heterogeneity. RESULTS: From a total of 417 records, 16 articles were retrieved for inclusion. The subgroup analysis revealed a higher MD rate in the studies that were conducted in America, and, likewise, said studies involved a longer follow-up time (>6 years). There was a non-significant lower risk of malignization among males. A negative correlation was observed between MD and the year in which the studies were published. CONCLUSIONS: The pooled MD of PVML was 65.8% (95% CI: 55.3-76.2, p < 0.001). Prospective studies of PVML must be designed using simple and universal clinical diagnostic criteria to be able to make an early diagnosis of this important OPMD and acknowledge the frequency of MD.

Malignant transformation of oral leukoplakia: Systematic review and meta-analysis of the last 5 years.

OBJECTIVE: Oral leukoplakia (OL) is the most frequently encountered oral potentially malignant disorder. The aims of this systematic review are to estimate the overall malignant transformation of OL and to assess the risk factors associated with malignant transformation of OL published in the last 5 years (2015-2020). MATERIALS AND METHODS: We performed a bibliographic search in PubMed, Scopus, Web of Science, Embase, and Cochrane databases with keywords "oral leukoplakia", "oral cancer", "oral carcinoma" and "oral squamous cell carcinoma". Meta-analysis was conducted using a random-effects model. RESULTS: Twenty-four studies were selected, that reported a total of 16,604 patients. Malignant transformation proportion varied between 1.1% and 40.8%. Female gender, non-homogeneous clinical type, and presence of epithelial dysplasia were significantly related to MT. Other risk factors previously suggested did not show significant results. CONCLUSIONS: The pooled proportion of malignant transformation MT was 9.8% (95% CI: 7.9-11.7). It is necessary to continue to conduct well-designed prospective clinicopathological studies on OL, using a uniform definition for OL to reduce the risk of bias for evaluating various factors associated with the MT.

Oral potentially malignant disorders: A consensus report from an international seminar on nomenclature and classification, convened by the WHO Collaborating Centre for Oral Cancer.

Oral potentially malignant disorders (OPMDs) are associated with an increased risk of occurrence of cancers of the lip or oral cavity. This paper presents an updated report on the nomenclature and the classification of OPMDs, based predominantly on their clinical features, following discussions by an expert group at a workshop held by the World Health Organization (WHO) Collaborating Centre for Oral Cancer in the UK. The first workshop held in London in 2005 considered a wide spectrum of disorders under the term "potentially malignant disorders of the oral mucosa" (PMD) (now referred to as oral potentially malignant disorders: OPMD) including leukoplakia, erythroplakia, proliferative verrucous leukoplakia, oral lichen planus, oral submucous fibrosis, palatal lesions in reverse smokers, lupus erythematosus, epidermolysis bullosa, and dyskeratosis congenita. Any new evidence published in the intervening period was considered to make essential changes to the 2007 classification. In the current update, most entities were retained with minor changes to their definition. There is sufficient evidence for an increased risk of oral cancer among patients diagnosed with "oral lichenoid lesions" and among those diagnosed with oral manifestations of 'chronic graft-versus-host disease'. These have now been added to the list of OPMDs. There is, to date, insufficient evidence concerning the malignant potential of chronic hyperplastic candidosis and of oral exophytic verrucous hyperplasia to consider these conditions as OPMDs. Furthermore, due to lack of clear evidence of an OPMD in epidermolysis bullosa this was moved to the category with limited evidence. We recommend the establishment of a global research consortium to further study the natural history of OPMDs based on the classification and nomenclature proposed here. This will require multi-center longitudinal studies with uniform diagnostic criteria to improve the identification and cancer risk stratification of patients with OPMDs, link them to evidence-based interventions, with a goal to facilitate the prevention and management of lip and oral cavity cancer.

Polymorphisms in alcohol and tobacco metabolism genes in head and neck cancer in the Basque Country.

BACKGROUND: The Basque Country has one of the highest rates of head and neck squamous cell carcinoma (HNSCC) in Europe, although tobacco and alcohol consumption are not high when compared to other European countries where HNSCC incidence is lower. Our aim was to determine the role of genetic variation with regard to the metabolism of alcohol and carcinogens from tobacco smoke in the Basque Country. METHODS: Fourteen polymorphisms in alcohol or tobacco metabolism genes were genotyped in 84 HNSCC patients and 242 healthy individuals from the Basque Country. RESULTS: ADH1B histidine allele (rs1229984), CYP2E1 rs3813867 heterozygous genotype, and GSTT1 deletion conferred protection against HNSCC (OR: 0.318 [0.04-0.75], OR: 0.13 [0.02-0.94], and OR: 0.12 [0.02-0.60], respectively) while GSTP1 (rs1695) Val/Val genotype was related to an increased risk (OR: 4.12 [1.11-15.31]). Regarding alcohol and tobacco habits, GSTT1 deletion was associated with tobacco usage, while the 3 polymorphisms tested in ALDH2 were associated with alcohol consumption. However, genotypic distributions of these 7 SNPs did not differ from those observed for other Caucasian populations where HNSCC incidence is lower. CONCLUSIONS: The identified genotypic variations in alcohol and tobacco metabolizing genes only by themselves do not seem to be responsible for the higher incidence of HNSCC observed in the Basque Country.

Ancient Schwannoma of the hard palate. An uncommon case report and review.

Schwannoma or neurilemmoma is an infrequent benign tumor in the oral cavity that originates from the Schwann cells on the neural sheath of the peripheral nerves. Schwannomas are frequently located in the soft tissues of head and neck region, but only a 1 to 12% of them are located in the oral cavity. Some histological variants of schwannoma have been described including the cellular, plexiform, epithelioid, ancient, and melanocytic types. The "ancient schwannoma" is an uncommon variant of this tumor that shows specific histological characteristics, and is rare in the oral cavity with less than 15 cases described on the literature. Most of them were located in the tongue or in the floor of the mouth, being the hard palate an extremely rare localization. We present a new clinical case of an ancient schwannoma with a long time of evolution, arising from the nasopalatine nerve, and located in the hard palate of a 35 year old female. We also review the main clinical and histological characteristics of this pathology. Key words:Ancient schwannoma, neurilemmoma, palate, schwannoma.

Role of cytochrome P-450 genetic polymorphisms in oral carcinogenesis.

Oral cancer is one of the most frequent head and neck cancers, and epidemiological studies have shown that smoking is a major risk factor in this pathology. However, as not all smokers develop oral cancer, some individuals must be more susceptible to develop this disease. This individual susceptibility has been related to different genetic variants in metabolizing enzymes. The cytochrome P-450 (CYP) family of enzymes metabolizes tobacco-related carcinogens producing reactive metabolites, which could cause DNA damage. Because of their functional role in the metabolism of tobacco-related compounds, the genetic polymorphisms found in the genes that code for CYP enzymes have been suggested to modulate oral cancer risk and contribute to individual susceptibility. In this review, we analyze and update the available evidence in the literature regarding the polymorphisms of CYP genes in relation to the susceptibility of developing oral cancer.

Proliferative multifocal leukoplakia better name that proliferative verrucous leukoplakia.

In this letter I propose the name "Proliferative Multifocal Leukoplakia" with the goal of reducing under-diagnosis of this disease, improve the early diagnosis, try to make an early therapy and control, and prevent its malignant transformation.

Overexpression of cyclooxygenase-2 as a biomarker in different subtypes of the oral lichenoid disease.

OBJECTIVE: Oral lichenoid disease (OLD) includes a number of chronic inflammatory processes including oral lichen planus (OLP) and oral lichenoid lesions (OLL) with controversial diagnosis and prognosis. Cyclooxygenase-2 (COX-2) is a key enzyme for inflammatory processes and cellular proliferation. Its overexpression in some premalignant chronic inflammatory diseases and malignant neoplasias could point to its potential as a prognostic factor. The aim of this study was to analyze the COX-2 expression in different subtypes of OLD because of its potential to be a marker of altered behavior. STUDY DESIGN: Forty-four samples from OLD patients were studied (30 females and 14 males) and classified according to their clinical (C1: only papular lesions/C2: papular and other lesions) and histological features (HT: OLP typical/HC: OLP compatible) according to published criteria. Standard immunohistochemical procedure was performed for COX-2 expression and a comparative and descriptive statistical analyses were performed. RESULTS: Epithelial COX-2 overexpression was observed in 24 (54.5%) cases (C1: 13 [54.2%]/C2: 11 [45.8%], HT: 9 [37.5%]/HC: 15 [62.5%], P = .032). Inflammatory COX-2 overexpression was observed in 14 (31.8%) cases (C1: 6 [42.9%]/C2: 8 [57.1%], HT: 4 [28.6%]/HC: 10 [71.4%], P = .032). CONCLUSION: Differences in COX-2 expression in subtypes of OLD may distinguish cases with a higher premalignant potential.

Oral cancer and polymorphism of ethanol metabolising genes.

Oral cancer is the sixth most common cancer worldwide and a major health problem in some parts of the world. Epidemiological studies have shown that habitual alcohol consumption could be a risk factor in oral carcinogenesis, although the true involvement of alcohol is unknown. Via alcohol dehydrogenase (ADH) and cytochrome P450 oxidase (CYP) alcohol is metabolized to acetaldehyde, a highly toxic compound, which plays an important role in carcinogenesis. Subsequently, and during the metabolizing process, acetaldehyde becomes acetate by acetaldehyde dehydrogenase (ALDH). Therefore, acetaldehyde levels are determined mainly by the action of ADH, CYP and ALDH. Recently, several studies have found that certain polymorphisms of genes encoding these enzymes confer a higher or lower metabolic activity and therefore different risk for certain malignancies such as oral cancer. In this review, we analyze the polymorphisms of alcohol metabolising enzymes in relation susceptibility to an oral cancer.

Oral lichenoid disease as a premalignant condition: The controversies and the unknown

We grouped as oral lichenoid disease (OLD) a series of chronic inflammatory processes with autoimmune base that affect the epithelium of the oral mucosa. This disease is present in 2% of the population with a marked predilection for the female gender, especially perimenopausal women. Clinically, it is characterized by the presence of lineal reticular papules and histologically by liquefaction degeneration of the basal layer of the epithelium associated with an inflammatory infiltrate with a “band-like” disposition on the lamina propria, composed primarily of T lymphocyte cells. Its pathogenicity is associated with deregulation of the cellular immune system, where the activated cytotoxic CD8 and the CD4 T helper lymphocytes induce apoptosis of the epithelial cells. Classically it has been considered a precancerous condition, although the malignant transformation does not exceed 1% of the cases. In recent years the differentiation between oral lichen planus (OLP) and oral lichenoid lesions (OLL) has become important, since the latter might have a greater malignant potential. In this paper, we analyse and update some controversial aspects of this frequent oral disease in relation to the diagnosis and malignant potential (AU)

Oral lichenoid disease as a premalignant condition: the controversies and the unknown.

We grouped as oral lichenoid disease (OLD) a series of chronic inflammatory processes with autoimmune base that affect the epithelium of the oral mucosa. This disease presents in 2% of the population with a marked predilection for the female gender, especially perimenopausal women. Clinically, it is characterized by the presence of lineal reticular papules and histologically by liquefaction degeneration of the basal layer of the epithelium associated with an inflammatory infiltrate with a "band-like" disposition on the lamina propria, composed primarily of T lymphocyte cells. Its pathogenicity is associated with deregulation of the cellular immune system, where the activated cytotoxic CD8 and the CD4 T helper lymphocytes induce apoptosis of the epithelial cells. Classically it has been considered a precancerous condition, although the malignant transformation does not exceed 1% of cases. In recent years the differentiation between oral lichen planus (OLP) and oral lichenoid lesions (OLL) has become important, since the latter might have a greater malignant potential. In this paper, we analyse and update some controversial aspects of this frequent oral disease in relation to the diagnosis and malignant potential.

Gorlin-Goltz syndrome: clinicopathologic aspects.

Gorlin-Goltz syndrome, also known as nevoid basal cell carcicoma syndrome, comes into being due to a genetic alteration produced by a mutation in the "Patched" tumour suppressor gene, and it is inherited in a dominant autosomal way, though sporadic cases have been found. This syndrome shows a high penetrance and variable expressiveness. It is about a multisystemic process that is characterised by the presence of multiple pigmented basocellular carcinomas, keratocysts in the jaws, palmar and/or plantar pits and calcification of the falxcerebri. Together with these major features a great number of processes considered as minor features have also been described. The latter include numerous skeletical, dermatology related and neurological anomalies among others. In some occasions, the presence of very aggressive basocellular carcinomas has been described as well as other malignant neoplasias. Due to the importance of oral maxillofacial manifestations of this syndrome, it is fundamental to know its characteristic in order to make a diagnosis, an early preventive treatment and establish right genetic advice. In this work the main clinicopathologic and the therapeutic aspects related to the syndrome under consideration have been revised and updated.

Gorlin-Goltz syndrome: Clinicopathologic aspects

Gorlin-Goltz syndrome, also known as nevoid basal cell carcicoma syndrome, comes into being due to a genetic alteration produced by a mutation in the “Patched” tumour suppressor gene, and it is inherited in a dominant autosomal way, though sporadic cases have been found. This syndrome shows a high penetrance and variable expressiveness. It is about a multisystemic process that is characterised by the presence of multiple pigmented basocellular carcinomas, keratocysts in the jaws, palmar and/or plantar pits and calcification of the falxcerebri. Together with these major features a great number of processes considered as minor features have also been described. The latter include numerous skeletical, dermatology related and neurological anomalies among others. In some occasions, the presence of very aggressive basocellular carcinomas has been described as well as other malignant neoplasias. Due to the importance of oral maxillofacial manifestations of this syndrome, it is fundamental to know its characteristic in order to make a diagnosis, an early preventive treatment and establish right genetic advice. In this work the main clinicopathologicand the therapeutic aspects related to the syndrome under consideration have been revised and updated

Letter to the Editor: Oral Lichenoid Disease. A new classification proposal

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Letter to the Editor: E-cadherin, laminin and collagen IV expression in the evolution from dysplasia to oral squamous cell carcinoma

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Immunoexpression of p53, Ki-67 and E-cadherin in basaloid squamous cell carcinoma of the larynx.

INTRODUCTION: Basaloid is a rare and poorly-differentiated variant of squamous cell carcinoma of the larynx, with an invasive solid growth of cells in a lobular configuration. Different molecular markers, such as p53, Ki-67 and E-cadherin, have been shown to be prognostic factors in head and neck cancer. OBJECTIVE: To evaluate the relationship between the immunoexpression of p53, Ki-67 and E-cadherin in relation to prognosis in basaloid squamous cell carcinoma of the larynx (BSCCL). PATIENTS AND METHODS: We retrospectively studied 11 cases of BSCCL, all male with a mean age of 62.4 years. Immunohistochemical analyses were performed on paraffin-embedded tissues using p53 (DO- 7), Ki-67 (MIB-1) and E-cadherin (36B5) antibodies. Quantitative assessments of the expression and descriptive statistical analyses were performed. RESULTS: In 72.7% of the cases, clinically advanced stages III-IV were diagnosed. Average survival time was 56.09 months, and 72.7% of patients died as a consequence of the tumour. Immunoreactivity of p53 (>10% of cells) was detected in the 81.8% of the cases. The 72.7% of the cases showed overexpression of Ki-67 (>50% of cells). The cases with low immunoexpression of Ki-67 and p53 had the best clinicopathological data. All cases showed a decreased expression of E-cadherin. CONCLUSIONS: BSCCL is an aggressive variant of the squamous cell carcinoma and has a high expression of p53 and Ki-67 with a low expression of Ecadherin. These results could be related to the aggressiveness of the disease and its poor prognosis.