Global prevalence of human papillomavirus-related oral and oropharyngeal squamous cell carcinomas: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review to determine the global prevalence of HPV in oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: Literature was searched through October 2022 in main databases to address the question "What is the global prevalence of Human Papillomavirus in oral and oropharyngeal cancer?" Studies had to identify HPV by PCR, ISH, or p16 immunohistochemistry to be eligible. Quality was assessed using the JBI checklist for prevalence studies. Meta-analyses were performed, and reporting followed PRISMA guidelines. RESULTS: Sixty-five studies were included, and most of them had methodological limitations related to sampling and the HPV detection tool. The pooled prevalence of HPV-positivity was 10% (event rate = 0.1; 95% CI: 0.07, 0.13; P < 0.01; I2 = 88%) in the oral cavity and 42% (event rate = 0.42; 95% CI: 0.36, 0.49; P = 0.02; I2 = 97%) in oropharynx. The highest HPV prevalence in OSCC was reached by Japan, meanwhile, in OPSCC, Finland and Sweden were the most prevalent. HPV16 is the genotype most frequent with 69% in OSCC and 89% in OPSCC, being the tonsils the intraoral location more affected by HPV (63%, p < 0.01, I2 76%). CONCLUSION: The evidence points to an apparent burden in HPV-related OPSCC, mostly in North America, Northern Europe, and Oceania, especially due to the HPV16 infection suggesting different trends across continents. CLINICAL RELEVANCE: This updated systematic review and meta-analysis provide sufficient evidence about the global HPV prevalence in OSCC and OPSCC and the most frequent HPV subtype worldwide.

Human Papillomavirus-Associated Oral Epithelial Dysplasia: Report of 5 Illustrative Cases from Latin America.

BACKGROUND: Human papillomavirus-associated oral epithelial dysplasia (HPV-OED) is a distinct oral epithelial disorder characterized by viral cytopathic changes caused by transcriptionally active high-risk HPV. The aim of the present study was to report 5 additional cases from Latin America. METHODS: Clinical data from five patients with HPV-OED were obtained from the archives of three oral pathology services from Brazil and Chile. All cases were submitted to morphological, p16 expression and in situ hybridization (ISH) for HPV analyses. RESULTS: Four patients were male and one patient was female, with a mean age of 55.4 years. Four patients were HIV seropositive and two were smokers. Three cases affected the buccal mucosa and commissure, one of which had an additional plaque in the soft palate, and one case each occurred on the floor of mouth and lower labial mucosa. Most cases presented as well-demarcated white plaques with a verrucous surface. One case presented multiple lesions ranging from normal to white-colored slightly elevated plaques with a cobblestone surface. Peripheral mucosal pigmentation was observed in two cases. All five cases presented with the characteristic microscopic features of HPV-OED, including severe dysplasia with numerous karyorrhectic and apoptotic cells, full-thickness "block positivity" for p16 and high Ki-67 index (> 90%) sharply demarcated from the adjacent non-dysplastic epithelium. Wide-spectrum DNA ISH-HPV was positive in 4 cases. All patients were treated with conservative surgical excision with no signs of recurrence after a mean of 39-month follow-up. CONCLUSION: This represents the first series of HPV-OED from Latin America; most cases presented as well-demarcated papillary white plaques affecting the buccal mucosa and commissure of HIV-positive middle-aged men, two of them exhibiting peripheral pigmentation caused by reactive melanocytes. The typical microscopic findings of HPV-OED were observed in all cases, which also showed strong p16 positivity in a continuous band through the full thickness of the epithelium and high Ki67.

Exuberant clear cell odontogenic carcinoma of the mandible harboring EWSR1 rearrangement: Report of a rare case and a literature review.

Clear cell odontogenic carcinoma (CCOC) is a rare malignant odontogenic tumour (MOT) that mainly affects the mandible, with a slight female predominance in adult patients. In this study, we described an exuberant CCOC in mandible of a 22-year-female patient. On radiographic examination, a radiolucent lesion in the region of tooth 36 to 44 with tooth displacement and alveolar cortical resorption was observed. Histopathological study revealed a malignant neoplasm of the odontogenic epithelium, composed of PAS-positive clear cells and immunoreactivity for CK5, CK7, CK19, p63. The Ki-67 index was low (<10 %). Fluorescent in situ hybridization revealed EWSR1 gene rearrangement. The diagnosis of CCOC was established and the patient was referred for surgical treatment.

Rhabdomyosarcoma with TFCP2 Rearrangement or Typical Co-expression of AE1/AE3 and ALK: Report of Three New Cases in the Head and Neck Region and Literature Review.

BACKGROUND: Rhabdomyosarcoma (RMS) harboring EWSR1/FUS-TFCP2 fusions has been recently described as a distinct form of RMS with an aggressive course and predilection for the craniofacial bones, especially the jaws. METHODS: We report three new cases of this rare entity, two from Brazil and one from Guatemala, with detailed clinicopathologic, immunohistochemical, and molecular descriptions. Additionally, we explored the English-language literature searching RMS with TFCP2 rearrangement or typical immunophenotype with co-expression of AE1/AE3 and ALK in the head and neck region. RESULTS: Case 1 is a 58-year-old male with a 3-month history of painful swelling in the anterior maxilla. Case 2 is a 22-year-old male presenting with right facial swelling and proptosis. Case 3 is a 43-year-old female with a rapidly growing tumor located in the zygomatic region. Imaging examinations revealed highly destructive intraosseous masses in the first two cases, and a soft tissue tumor with bone invasion in case 3. Microscopically, all cases showed a hybrid spindle and epithelioid phenotype of tumor cells which expressed desmin, myogenin and/or Myo-D1, AE1/AE3, and ALK. FISH confirmed molecular alterations related to TFCP2 rearrangement in Cases 1-2. In case 3, there was no available material for molecular analysis. The patients were subsequently referred to oncologic treatment. Additionally, we summarized the clinicopathologic, immunohistochemical, and molecular features of 27 cases of this rare RMS variant in the head and neck region reported in the English-language literature. CONCLUSION: RMS with TFCP2 rearrangement is a rare and aggressive tumor with a particular predilection for craniofacial bones, especially the jaws. Knowing its clinicopathologic and immunohistochemical profile can avoid misdiagnosis.

Clinicoradiological spectrum of primary aneurysmal bone cysts of the maxillofacial region: A series of 31 cases.

OBJECTIVES: The aim of the current study was to analyse the demographic, clinical and radiological features of primary aneurysmal bone cysts (ABCs) involving the maxillofacial region. METHODS: Histologically confirmed cases affecting the maxillofacial region were retrospectively reviewed over a 21-year period (2000-2021). Cases were collected from the archives of five Oral Pathology laboratories from three countries: South Africa, Guatemala and Brazil. The information was analysed, with emphasis on the clinical and radiological spectrum. RESULTS: Following the inclusion criteria, a total of 31 cases of primary ABCs were included in the study. A nearly equal male-to-female distribution was seen, with ABCs occurring in males at an earlier age compared to females. Localised swelling was the main clinical presentation. ABCs had a mandibular predominance, particularly in the posterior regions. All ABCs presented as blow-out expansile well-demarcated radiolucent lesions with the majority having a multilocular appearance. Cortical expansion was seen in 91% of cases with loss of cortical integrity being common (78%). CONCLUSION: Primary ABCs involving the maxillofacial region are extremely rare with the majority of current published literature consisting of isolated case reports. The current study is the first large series detailing the radiological features.

Clinical and radiologic spectrum of glandular odontogenic cysts: A multicenter study of 92 cases.

OBJECTIVE: The purpose of this multicenter retrospective study was to report the clinical and radiologic features of 92 glandular odontogenic cysts (GOCs) diagnosed over a 20-year period. STUDY DESIGN: Histologically confirmed cases of GOC were retrospectively reviewed from 4 oral pathology laboratories in South Africa and Brazil to categorize the clinical and radiologic spectrum of GOCs. RESULTS: The mean age of patients was 46 years (range 17-87) with a male-to-female ratio of 1.2:1. GOCs had a mandibular predilection (68%), with 42% of all cases located anteriorly. Additionally, 42% of cases crossed the midline. Radiologically, most lesions were unilocular (53%) and uniformly radiolucent (97%), with well-demarcated borders (93%). Cortical expansion (62%), loss of cortical integrity (71%), and maxillary sinus (67%) and nasal cavity encroachment (72%) were common findings. Significant differences in lesions between the 2 countries were discovered in sex predilection, clinical signs and symptoms, and lesion locations within the mandible and maxilla. CONCLUSION: GOCs present with a wide spectrum of clinical and radiologic features, ranging from cysts with typical GOC-like presentations to more aggressive lesions. The need for advanced imaging in the surgical planning of GOCs exhibiting radiologic signs of aggression is justified based on the high recurrence rate.

Acquired oral syphilis: A multicenter study of 339 patients from South America.

OBJECTIVE: To report the clinicopathologic features of acquired oral syphilis cases in South American countries. MATERIALS AND METHODS: Clinical data were retrospectively collected from the records of 18 oral diagnostic services in Argentina, Brazil, Chile, Colombia, Venezuela, Uruguay, and Peru. Serologies of nontreponemal and treponemal tests were used for diagnosis. RESULTS: The series comprised 339 cases of acquired oral syphilis. Secondary syphilis ranked as the most common stage (86.7%). Lesions were more frequent among males (58.0%) and young adults with a mean age of 33.3 years. Individuals aged 20-29 years were most affected (35.3%). The most commonly involved sites were the tongue (31.6%), lip/labial commissure (25.1%), and hard/soft palate (20.4%). Clinically, acquired oral syphilis usually presented as mucous patches (28.4%), papules (25.7%), and ulcers (18.1%). Skin manifestations occurred in 67.7% of individuals, while lymphadenopathy and fever were observed in 61.3% and 11.6% of all subjects, respectively. Most patients were treated with the benzathine penicillin G antibiotic. CONCLUSION: This report validates the spread of acquired oral syphilis infection among young adults in South America. Our directives include accessible diagnostic tools for proper disease screening, surveillance, and counselling of affected individuals, especially in low- and middle-income countries.

Oral Lymphoepithelial Cyst: A Collaborative Clinicopathologic Study of 132 Cases from Brazil.

The oral lymphoepithelial cyst (OLC) is an uncommon lesion whose pathogenesis remains poorly understood. The aim of this study was to report the clinicopathologic features of the OLCs and to verify a possible association between OLCs and subgemmal neurogenous plaque (SNP) in the posterior lateral region of the tongue. A retrospective descriptive cross-sectional study was carried out. A total of 106,282 biopsy records of oral and maxillofacial lesions from six oral pathology services in Brazil were analyzed. All cases of OLCs were reviewed, and clinical and histopathological data were collected. Immunohistochemical reactions for S-100 protein were performed to confirm the diagnosis of SNP. Among all lesions, there were 132 (0.11%) cases of OLCs. The series comprised 83 females (62.9%) and 49 males (37.1%), with a 1.7:1 female-to-male ratio and a mean age of 45.8 ± 17.7 years. Most cases involved the tongue (n = 80; 62.0%) and presented clinically as asymptomatic papules or nodules with a yellow or whitish color. Microscopically, most of the cysts were entirely lined by parakeratinized stratified epithelium (n = 89; 67.4%) and filled with desquamated cells, keratin debris, amorphous eosinophilic material, and inflammatory cells in varying amounts. Connection with the epithelium of oral mucosa was observed in 18 cases (13.6%). SNP was found in 9/80 (11.2%) cases involving the tongue. The clinical and demographic features of OLCs were similar to those described in previous studies. Overall, this lesion has a predilection for the posterior region of the tongue of female adults. Clinicians must include the OLC in the differential diagnosis of yellow/white papules and nodules of the oral cavity.

The role of osteopontin in oral cancer: A brief review with emphasis on clinical applications.

Osteopontin (OPN) is a calcium-binding glycol-phosphoprotein present in many physiologic and pathological processes. This protein can control bone cell adhesion, osteoclastic activity, and bone matrix mineralization. However, its participation in pathological processes such as atherosclerosis, sarcoidosis, tuberculosis, and cancer have been described. Some studies have shown that OPN may participate in the development and progression of oral cancer. Although the role of OPN in oral cancer is not fully understood, some studies have suggested that this protein may induce malignant phenotype of cells by activation of PI3K/AKT/mTOR pathway, which favors cell proliferation, invasion, metastasis, angiogenesis, and failure of treatment. This review discusses the possible mechanism of involvement of OPN in oral cancer and its potential clinical application in diagnosis and prognosis.

Mature T/NK-Cell lymphomas of the oral and maxillofacial region: A multi-institutional collaborative study.

BACKGROUND: The diagnosis of oral and maxillofacial mature T/NK-cell neoplasms is challenging because of their rarity, morphological heterogeneity and complex immunophenotype with scarce available data describing their clinical and microscopic aspects. Therefore, in this study, we investigated a series of mature T/NK-cell neoplasms affecting this anatomical region and provided an updated literature review. METHODS: Cases diagnosed as mature T/NK-cell lymphomas affecting the oral and maxillofacial region were retrospectively retrieved from six pathology files and their diagnoses were confirmed using haematoxylin and eosin-stained slides, immunohistochemical reactions and in situ hybridization for Epstein-Barr virus (EBV) detection. Patients' clinical data were collected from their pathology forms. RESULTS: A total of 22 cases were included in this study. Eleven (50%) consisted of extranodal NK/T-cell lymphomas, nasal type; eight (36.4%) were peripheral T-cell lymphomas, NOS; two (9.1%) were adult T-cell leukaemia/lymphomas, and one (4.5%) was an ALK-positive anaplastic large cell lymphoma. Overall, males predominated, with a mean age of 55.7 years. The palate was the most affected site (50%), and tumours usually presented as destructive and painful ulcers. EBV was present in all cases of extranodal NK/T-cell lymphoma nasal type but was absent in the other subtypes. CONCLUSION: Among mature T/NK-cell lymphomas of the oral and maxillofacial region, extranodal NK/T-cell lymphoma, nasal type and peripheral T-cell lymphoma, NOS predominated. Older men were the most affected patients, and this heterogeneous group of neoplasms has a very aggressive clinical behaviour.

Fully digital pathology laboratory routine and remote reporting of oral and maxillofacial diagnosis during the COVID-19 pandemic: a validation study.

The role of digital pathology in remote reporting has seen an increase during the COVID-19 pandemic. Recently, recommendations had been made regarding the urgent need of reorganizing head and neck cancer diagnostic services to provide a safe work environment for the staff. A total of 162 glass slides from 109 patients over a period of 5 weeks were included in this validation and were assessed by all pathologists in both analyses (digital and conventional) to allow intraobserver comparison. The intraobserver agreement between the digital method (DM) and conventional method (CM) was considered almost perfect (κ ranged from 0.85 to 0.98, with 95% CI, ranging from 0.81 to 1). The most significant and frequent disagreements within trainees encompassed epithelial dysplasia grading and differentiation among severe dysplasia (carcinoma in situ) and oral squamous cell carcinoma. The most frequent pitfall from DM was lag in screen mirroring. The lack of details of inflammatory cells and the need for a higher magnification to assess dysplasia were pointed in one case each. The COVID-19 crisis has accelerated and consolidated the use of online meeting tools, which would be a valuable resource even in the post-pandemic scenario. Adaptation in laboratory workflow, the advent of digital pathology and remote reporting can mitigate the impact of similar future disruptions to the oral and maxillofacial pathology laboratory workflow avoiding delays in diagnosis and report, to facilitate timely management of head and neck cancer patients. Graphical abstract.

Calcifying odontogenic cysts: A 20-year retrospective clinical and radiological review.

OBJECTIVE: Calcifying odontogenic cysts (COCs) exhibit diverse clinical behaviours and may be associated with other benign odontogenic tumours. In this study, the clinical and radiological features of COCs were analysed according to subtypes based on the classification by Praetorius et al. Emphasis was placed on cases exhibiting atypical or aggressive radiological appearances. This information may assist the clinician to better understand the radiological spectrum of COCs. METHODS: Histologically confirmed cases of COCs were retrospectively reviewed in a 20-year period from three tertiary institutions. The following clinical information was reviewed: patient demographics, main complaint, clinical duration, anatomical site and detailed radiological features. RESULTS: Twenty-seven cases of COCs were included in the study. Asymptomatic swelling was the main clinical presentation with infrequent reports of associated pain. COCs had an anterior mandibular predilection. Well-demarcated borders were seen in all cases with isolated cases showing focal areas with loss of demarcation. Unilocular lesions were more common than multilocular variants. Internal calcifications were frequent and six cases presented with associated odontomas. Maxillary COCs resulted in the displacement of the maxillary sinus and/or nasal cavity walls. Radiological signs of aggression, including cortical destruction, were noted in a few cases. CONCLUSION: Given the fact that COCs can present with a spectrum of clinical behaviours and radiological presentations, the academic debate regarding the cystic versus neoplastic nature of the entity is justifiable. The cases in the current sample presented with diverse presentations, ranging from indolent to lesions with significant growth and aggression.

Central odontogenic fibroma: an international multicentric study of 62 cases.

OBJECTIVE: The aim of this study was to report the clinicopathologic features of 62 cases of central odontogenic fibroma (COdF). STUDY DESIGN: Clinical and radiographic data were collected from the records of 13 oral pathology laboratories. All cases were microscopically reviewed, considering the current World Health Organization classification of tumors and were classified according to histopathologic features. RESULTS: There were 43 females and 19 males (average age 33.9 years; range 8-63 years). Clinically, COdF lesions appeared as asymptomatic swellings, occurring similarly in the maxilla (n = 33) and the mandible (n = 29); 9 cases exhibited palatal depression. Imaging revealed well-defined, interradicular unilocular (n = 27), and multilocular (n = 12) radiolucencies, with displacement of contiguous teeth (55%) and root resorption (46.4%). Microscopically, classic features of epithelial-rich (n = 33), amyloid (n = 10), associated giant cell lesion (n = 7), ossifying (n = 6), epithelial-poor (n = 3), and granular cell (n = 3) variants were seen. Langerhans cells were highlighted by CD1a staining in 17 cases. Most patients underwent conservative surgical treatments, with 1 patient experiencing recurrence. CONCLUSIONS: To the best of our knowledge, this study represents the largest clinicopathologic study of COdF. Most cases appeared as locally aggressive lesions located in tooth-bearing areas in middle-aged women. Inactive-appearing odontogenic epithelium is usually observed within a fibrous/fibromyxoid stroma, occasionally exhibiting amyloid deposits, multinucleated giant cells, or granular cells.

An international collaborative study of 105 new cases of adenomatoid odontogenic tumors.

OBJECTIVE: The aim of this study was to report the clinicopathologic features of 105 new cases of adenomatoid odontogenic tumor (AOT) from Brazil, Guatemala, Mexico, and South Africa. STUDY DESIGN: Clinical and radiographic data were collected from records of 5 oral pathology laboratories, and all cases were microscopically reviewed. RESULTS: This series of cases included 36 (34.2%) from South Africa; 33 (31.4%) from Brazil; 23 (21.9%) from Mexico; and 13 (12.3%) from Guatemala. Seventy-two patients (68.5%) were females and 33 patients (31.4%) were males, with an average age of 19.2 years. The tumors predominantly affected the anterior maxilla (48.5%), followed by the anterior mandible (29.5%); posterior mandible (15.2%); and posterior maxilla (6.6%). Sixty-three tumors (63.6%) were follicular, 34 (34.3%) were extrafollicular, and 2 (2%) were peripheral. In most cases, the tumors caused considerable cortical expansion (average size 3.4 cm). Microscopically, most cases showed rosette-like and duct-like structures. CONCLUSIONS: This is one of the largest case series of AOTs reported in the literature and the first multicenter study involving populations from Latin America and South Africa. In a fifth of the present cases, the posterior regions of the gnathic bones were affected and the tumors demonstrated larger sizes compared with cases occurring in other populations.

Oral leukoplakia and erythroplakia in young patients: a systematic review.

OBJECTIVE: The aim of this study was to estimate the frequency of oral leukoplakia and oral erythroplakia in young patients. STUDY DESIGN: The systematic review was based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and performed in the following electronic databases: PubMed, Scopus, and Embase. The studies included were cross-sectional, cohort, and diagnostic, which provided with clinical and microscopic data of patients younger than 40 years. The Critical Appraisal Checklist for Prevalence Studies from the Joanna Briggs Institute and the Quality Assessment Tool for Diagnostic Accuracy Studies were used to assess the risk of bias. RESULTS: Five studies met eligibility criteria and were included. The total number of patients from the studies was 1246, of which 115 were young patients (9.2%) with oral leukoplakia as the only oral potentially malignant disorder reported. Oral epithelial dysplasia was identified in 40 cases (34.7%), of which 8 (6.9%) presented malignant transformation. CONCLUSIONS: The frequency of oral leukoplakia is low in young patients. Observational studies are necessary for understanding oral leukoplakia and other oral potentially malignant disorders in younger patients.

Eruption sequestrum: an inflamed odontogenic hamartoma.

Eruption sequestrum (ES) is a single or even multiple, small whitish calcified masses found within the soft tissue of the opercula overlying the crown of erupting permanent molars of children. We herein report a well-documented case of ES, offering a review of published cases in the English literature. An otherwise healthy 6-year-old girl was seen for routine dental examination. A fragment of hard whitish tissue was observed in the gingiva overlying the erupting lower first permanent molar, which showed radiographic appearance of a faint round radiopacity above and separated from the occlusal surface of the related tooth. The patient was submitted to an excisional biopsy, and gross examination showed a hardened whitish fragment surrounded by gingival mucosa. Microscopic examination revealed odontogenic epithelium in association with chronic inflammatory infiltrate and small blood vessels in the connective tissue. Small concentric basophilic calcifications, round osteodentin, and pulp-like structures were also observed. The microscopic evaluation of additional cases of ES may improve the understanding of this uncommon inflamed odontogenic hamartoma.

Anaplastic Large Cell Lymphoma with Oral Manifestation: A Series of Four Cases and Literature Review.

The aim of this study was to describe the clinicopathological and immunohistochemical features of four cases of anaplastic large cell lymphoma (ALCL) diagnosed through oral manifestations. Clinical data were collected from charts of a single oral pathology laboratory over a 5-year period (2014-2019) and all cases were evaluated by conventional hematoxylin and eosin staining and an extended immunohistochemical panel comprising CD45, CD20, CD3, CD4, CD7, CD30, CD99, CD138, cytokeratin AE1/AE3, EMA, ALK, MUM-1 and Ki-67. The study included 3 male (75%) and 1 female (25%) patients, with a median age of 44 years. The most common intraoral affected site was the alveolar ridge (50%). Clinically, all cases were characterized as an ulcerated bleeding mass. Microscopically, proliferation of anaplastic large lymphoid cells with medium to large-sized, abundant amphophilic to eosinophilic cytoplasm and eccentric nuclei were observed. All cases were positive for CD30, while two cases strongly express ALK. Two patients died of the disease. Careful correlation of clinical, morphological and immunohistochemical data are necessary to establish the diagnosis of oral manifestation of ALCL since its microscopical features may mimic other malignant tumors. Clinicians and pathologists should consider ALCL in the differential diagnosis when evaluating oral ulcerated swellings exhibiting large lymphoid cells in patients with lymphadenopathy.

Clinical predictors of malignancy in palatal salivary gland tumors.

OBJECTIVES: To establish a predictive clinical index of malignancy risk in palatal salivary gland tumors (PSGT). MATERIALS AND METHODS: One hundred cases of PSGT were evaluated. Clinical data were retrieved from the patient's files. Representative clinical photographs of each tumor were evaluated to identify clinical features suggestive of a malignant tumor. Features significantly associated with malignancy were included in a binary logistic regression model. RESULTS: Malignant tumors were more common in the hard palate, in women and in older patients. Features associated with a malignant diagnosis included pain (p = .017), irregular surface (p = .004), bluish/purple coloration (p < .001), ulceration (p = .005), and telangiectasia (p = .015). After multivariate logistic regression, pain (OR: 4.017; 95% CI: 1.198-13.471; p = .024) and color alteration (OR: 7.243; 95% CI: 2.068-25.363; p = .002) were independently associated with malignancy. Including these factors in a predictive index, the proportion of malignant tumors in patients presenting none, one and two factors were 25% (95% CI: 0.13-0.40), 67% (95% CI: 0.48-0.83), and 85% (95% CI: 0.42-0.99), respectively. CONCLUSION: Pain and color alteration might be independent predictors of malignancy in PSGT, which could support the decision to perform an incisional or excisional biopsy.