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Oral Diseases Nov 2021Oral 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... (Review)
Review
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.
Topics: Cell Transformation, Neoplastic; Consensus; Humans; Leukoplakia, Oral; Lichen Planus, Oral; Mouth Neoplasms; Precancerous Conditions; World Health Organization
PubMed: 33128420
DOI: 10.1111/odi.13704 -
Head and Neck Pathology Sep 2019Leukoplakia and erythroplakia are two entities under the moniker of "oral potentially malignant disorders" that are highly associated with the presence of oral... (Review)
Review
Leukoplakia and erythroplakia are two entities under the moniker of "oral potentially malignant disorders" that are highly associated with the presence of oral epithelial dysplasia (OED) at first biopsy, while lesions of submucous fibrosis develop OED after being present for years. Importantly, traumatic/frictional keratoses are often mistaken clinically for leukoplakia and it is important for the pathologist to recognize and report them as such. The features of OED have been well-described and other architectural features will be discussed here, in particular verrucous and papillary architecture, bulky epithelial proliferation and epithelial atrophy. Proliferative leukoplakia, verrucous or otherwise, often show only hyperkeratosis in early lesions, with development of OED occurring over time, and squamous cell carcinoma developing in the majority of cases over time. The concept of hyperkeratosis without features of OED and that is not reactive, is likely a precursor to the dysplastic phenotype. Many cases of leukoplakia exhibiting OED are associated with a band of lymphocytes at the interface and these should not be mistaken for oral lichen planus.
Topics: Humans; Leukoplakia, Oral; Mouth Mucosa
PubMed: 30887394
DOI: 10.1007/s12105-019-01020-6 -
Head and Neck Pathology Mar 2022The fifth chapter of the upcoming fifth edition of the 2022 World Health Organization Classification of Tumours of the Head and Neck titled Tumours of the oral cavity... (Review)
Review
The fifth chapter of the upcoming fifth edition of the 2022 World Health Organization Classification of Tumours of the Head and Neck titled Tumours of the oral cavity and mobile tongue, has had some modifications from the 2017 fourth edition. A new section "Non-neoplastic Lesions", introduces two new entries: necrotizing sialometaplasia and melanoacanthoma. The combined Oral potentially malignant disorders and Oral epithelial dysplasia section in the 2015 WHO has now been separated and submucous fibrosis and HPV-associated dysplasia are also discussed in separate sections. Carcinoma cuniculatum and verrucous carcinoma are described in dedicated sections, reflecting that the oral cavity is the most common location in the head and neck for both these entities which have distinct clinical and histologic features from conventional squamous cell carcinoma. This review summarizes the changes in Chapter 5 with special reference to new additions, deletions, and sections that reflect current clinical, histological, and molecular advances.
Topics: Acanthoma; Carcinoma, Verrucous; Humans; Mouth Neoplasms; Oral Submucous Fibrosis; Sialometaplasia, Necrotizing; Tongue; Tongue Neoplasms; World Health Organization
PubMed: 35312982
DOI: 10.1007/s12105-021-01402-9 -
Frontiers in Pharmacology 2022Among oral diseases, oral cancer is a critical health issue due to its life-threatening potential. Globocan, in its 2020 report, estimated ∼0.37 million new cases of... (Review)
Review
Among oral diseases, oral cancer is a critical health issue due to its life-threatening potential. Globocan, in its 2020 report, estimated ∼0.37 million new cases of oral cancer, with the majority of them coming from the Asian continent. The WHO has anticipated a rise in the incidences of oral cancer in the coming decades. Various factors, such as genetic, epigenetic, microbial, habitual, and lifestyle factors, are closely associated with oral cancer occurrence and progression. Oral lesions, inherited genetic mutations (dyskeratosis congenital syndrome), and viral infections (HPV) are early signs of oral cancer. Lesions with dysplastic features have been categorized under oral potentially malignant disorders (OPMDs), such as oral leukoplakia, erythroplakia, oral submucous fibrosis (OSMF), and proliferative verrucous leukoplakia, are assumed to have a high risk of malignancy. The incidence and prevalence of OPMDs are recorded as being high in South-Asian countries. Early detection, prevention, and treatment of OPMDs are needed to prevent its malignant transformation into oral cancer. Many advanced diagnostic techniques are used to predict their progression and to assess the risk of malignant transformation. This communication provides insight into the importance of early detection and prevention of OPMDs.
PubMed: 35517828
DOI: 10.3389/fphar.2022.825266 -
American Family Physician Apr 2022Familiarity with common oral conditions allows clinicians to observe and treat patients in the primary care setting or refer to a dentist, oral surgeon,...
Familiarity with common oral conditions allows clinicians to observe and treat patients in the primary care setting or refer to a dentist, oral surgeon, otolaryngologist, or other specialist. Recurrent aphthous stomatitis (canker sores) is the most common ulcerative condition of the oral cavity. Recurrent herpes simplex labialis and stomatitis also commonly cause oral ulcers. Corticosteroids, immunocompromise, antibiotics, and dentures can predispose patients to oral candidiasis. Benign migratory glossitis (geographic tongue) occurs in up to 3% of the population but generally lacks symptoms, although some people experience food sensitivity or a burning sensation. Hairy tongue is associated with a low fiber diet, tobacco and alcohol use, and poor oral hygiene in older male patients. Generally, hairy tongue is asymptomatic except for an unattractive appearance or halitosis. Tobacco and alcohol use can cause mucosal changes resulting in leukoplakia and erythroplakia. These can represent precancerous changes and increase the risk of squamous cell carcinoma. Mandibular and maxillary tori are common bony cortical outgrowths that require no treatment in the absence of repeat trauma from chewing or interference with dentures. Oral lichen planus occurs in up to 2% of individuals and can present as lacy reticulations or oral erosions and ulcerations. Traumatic buccal mucosal fibromas and labial mucoceles from biting can be excised.
Topics: Aged; Glossitis, Benign Migratory; Humans; Male; Mouth Diseases; Mouth Mucosa; Oral Ulcer; Stomatitis, Aphthous; Tongue, Hairy
PubMed: 35426641
DOI: No ID Found -
Hematology. American Society of... Dec 2022Numerous genetic discoveries and the advent of clinical telomere length testing have led to the recognition of a spectrum of telomere biology disorders (TBDs) beyond the... (Review)
Review
Numerous genetic discoveries and the advent of clinical telomere length testing have led to the recognition of a spectrum of telomere biology disorders (TBDs) beyond the classic dyskeratosis congenita (DC) triad of nail dysplasia, abnormal skin pigmentation, and oral leukoplakia occurring with pediatric bone marrow failure. Patients with DC/TBDs have very short telomeres for their age and are at high risk of bone marrow failure, cancer, pulmonary fibrosis (PF), pulmonary arteriovenous malformations, liver disease, stenosis of the urethra, esophagus, and/or lacrimal ducts, avascular necrosis of the hips and/or shoulders, and other medical problems. However, many patients with TBDs do not develop classic DC features; they may present in middle age and/or with just 1 feature, such as PF or aplastic anemia. TBD-associated clinical manifestations are progressive and attributed to aberrant telomere biology caused by the X-linked recessive, autosomal dominant, autosomal recessive, or de novo occurrence of pathogenic germline variants in at least 18 different genes. This review describes the genetics and clinical manifestations of TBDs and highlights areas in need of additional clinical and basic science research.
Topics: Humans; Child; Dyskeratosis Congenita; Telomere; Germ-Line Mutation; Bone Marrow Failure Disorders; Anemia, Aplastic
PubMed: 36485133
DOI: 10.1182/hematology.2022000394 -
The Journal of Clinical Investigation Oct 2022Characterization of the dynamic change in the immunological landscape during malignant transformation from precancerous lesions to cancerous lesions in squamous cell...
Characterization of the dynamic change in the immunological landscape during malignant transformation from precancerous lesions to cancerous lesions in squamous cell carcinoma (SCC) is critical for the application of immunotherapy. Here, we performed single-cell RNA-Seq (scRNA-Seq) of 131,702 cells from 13 cancerous tissues of oral squamous cell carcinoma (OSCC), 3 samples of precancerous oral leukoplakia, and 8 adjacent normal samples. We found that tumor-infiltrating CD4+ and CD8+ T cells were functionally inhibited by immunosuppressive ligands expressed on various types of myeloid cells or neutrophils in the process of oral carcinogenesis. Notably, we identified a subset of myofibroblasts that exclusively expressed tryptophan 2,3-dioxygenase (TDO2). These TDO2+ myofibroblasts were located distally from tumor nests, and both CD4+ and CD8+ T cells were enriched around them. Functional experiments revealed that TDO2+ myofibroblasts were more likely to possess the ability for chemotaxis toward T cells but induced the transformation of CD4+ T cells into Tregs and caused CD8+ T cell dysfunction. We further showed that use of the TDO2 inhibitor LM10 attenuated the inhibitory states of T cells, restored the T cell antitumor response, and prevented the progression of OSCC malignant transformation in murine models. Our study reveals a multistep transcriptomic landscape of OSCC and demonstrates that TDO2+ myofibroblasts are potential targets for immunotherapy.
Topics: Animals; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Ligands; Mice; Mouth Neoplasms; Myofibroblasts; Precipitins; Squamous Cell Carcinoma of Head and Neck; Tryptophan Oxygenase
PubMed: 35972800
DOI: 10.1172/JCI157649 -
Atencion Primaria Jan 2020
Topics: Female; Humans; Leukoplakia, Oral; Middle Aged
PubMed: 31029457
DOI: 10.1016/j.aprim.2019.02.008 -
Journal of the National Cancer Institute Oct 2020The optimal clinical management of oral precancer remains uncertain. We investigated the natural history of oral leukoplakia, the most common oral precancerous lesion,...
BACKGROUND
The optimal clinical management of oral precancer remains uncertain. We investigated the natural history of oral leukoplakia, the most common oral precancerous lesion, to estimate the relative and absolute risks of progression to cancer, the predictive accuracy of a clinician's decision to biopsy a leukoplakia vis-à-vis progression, and histopathologic predictors of progression.
METHODS
We conducted a retrospective cohort study (1996-2012) of patients with oral leukoplakia (n = 4886), identified using electronic medical records within Kaiser Permanente Northern California. Among patients with leukoplakia who received a biopsy (n = 1888), we conducted a case-cohort study to investigate histopathologic predictors of progression. Analyses included indirect standardization and unweighted or weighted Cox regression.
RESULTS
Compared with the overall Kaiser Permanente Northern California population, oral cancer incidence was substantially elevated in oral leukoplakia patients (standardized incidence ratio = 40.8, 95% confidence interval [CI] = 34.8 to 47.6; n = 161 cancers over 22 582 person-years). Biopsied leukoplakias had a higher oral cancer risk compared with those that were not biopsied (adjusted hazard ratio = 2.38, 95% CI = 1.73 to 3.28). However, to identify a prevalent or incident oral cancer, the biopsy decision had low sensitivity (59.6%), low specificity (62.1%), and moderate positive-predictive value (5.1%). Risk of progression to oral cancer statistically significantly increased with the grade of dysplasia; 5-year competing risk-adjusted absolute risks were: leukoplakia overall = 3.3%, 95% CI = 2.7% to 3.9%; no dysplasia = 2.2%, 95% CI = 1.5% to 3.1%; mild-dysplasia = 11.9%, 95% CI = 7.1% to 18.1%; moderate-dysplasia = 8.7%, 95% CI = 3.2% to 17.9%; and severe dysplasia = 32.2%, 95% CI = 8.1%-60.0%. Yet 39.6% of cancers arose from biopsied leukoplakias without dysplasia.
CONCLUSIONS
The modest accuracy of the decision to biopsy a leukoplakia vis-à-vis presence or eventual development of oral cancer highlights the need for routine biopsy of all leukoplakias regardless of visual or clinical impression. Leukoplakia patients, particularly those with dysplasia, need to be closely monitored for signs of early cancer.
Topics: Adult; Aged; California; Cohort Studies; Disease Progression; Female; Humans; Leukoplakia, Oral; Male; Middle Aged; Mouth Neoplasms; Precancerous Conditions; Retrospective Studies; Risk
PubMed: 31860085
DOI: 10.1093/jnci/djz238