Oral Verrucous Carcinoma Research Articles

Clinicopathologic Features of Oral Verrucous Carcinoma: A Systematic Review and Meta-Analysis.

To further characterize the clinicopathologic features of oral verrucous carcinoma. In accordance with PRISMA guidelines, a systematic review of the Medline, Web of Science, Embase, and Cochrane databases was performed in search of articles evaluating clinicopathologic features of oral verrucous carcinoma. Primary outcomes of interest included tumor subsites, T-staging, rates of cervical lymph node metastases, rates of distant metastases, 5-year survival (overall, disease-free, or disease-specific), and recurrence rates. Meta-analysis was performed using a random effects model. Nineteen articles with a total of 1458 subjects were ultimately included in the analysis. There were 17 studies with a total of 1353 patients reporting verrucous carcinoma subsites and the buccal mucosa (59.2%, 55.1%-63.3%) (I2 = 98.1%) had the highest incidence of involvement. There were 10 papers with 277 patients reporting on rates of cervical lymph node metastases from surgical pathology yielding a pooled rate of 0% (0%-2.3%) (I2 = 1%). There were 14 studies with a collective 712 patients commenting on rates of distant metastases and collectively, none were reported, yielding a pooled rate of 0% (0%-0%) (I2 = 0%). Five year survival data was generally favorable relative to oral squamous cell carcinoma but was insufficient for meta-analysis. An international collection of evidence supports that pure oral verrucous carcinoma is a relatively indolent, non-metastasizing malignancy associated with areca nut consumption. A reliance on traditional squamous cell carcinoma staging and treatment algorithms for verrucous carcinoma patients can predispose to overtreatment.

Evaluation of Tumor-Associated Macrophages and Micro-Vessel Density in Verrucous Carcinoma and Squamous Cell Carcinoma of the Oral Cavity.

Tumor-associated macrophages (TAMs) are a crucial cellular component of human tumors, but their exact roles in tumor growth and angiogenesis during cancer progression are still subject to debate. The present study aimed to explore the impact of TAMs on tumor progression and angiogenesis in oral squamous cell carcinoma (OSCC) and oral verrucous carcinoma (OVC). For this cross-sectional study, 60 samples consisting of 40 OSCC and 20 OVC samples were chosen. Immunohistochemical staining was performed on the samples using anti-CD68 and anti-CD31 monoclonal antibodies to evaluate the frequency of TAMs and micro-vessel density (MVD), respectively. The data were analyzed using statistical software SPSS (v. 23) and through the independent samples Student t-test, one-way analysis of variance, and Pearson's correlation coefficient. The results of our study revealed that the mean number of TAMs and MVD were significantly greater in OSCC samples compared to OVC samples (P = 0.001) (P = 0.004). Also, the average number of TAMs and MVD increased in the high grade of OSCC; however, the correlation between both parameters and histopathological grades of OSCC was significant only for MVD. Our study found no significant correlation between TAMs and MVD (P = 0.005). Based on the results of our study, both TAMs and MVD were found to be significantly higher in OSCC samples compared to OVC samples. These findings suggest that the progression of oral cancer is associated with an increase in TAMs and vascular density. Additionally, the use of CD68 and CD31 markers may help in differentiating between these two types of tumors.

Traversing the Terrain: Potential Pitfalls within the AJCC 8th Edition Staging System for Lip and Oral Cavity Cancers.

In 1977, the American Joint Committee on Cancer (AJCC) introduced the inaugural Cancer Staging Manual, which implemented the T (tumor extent), N (regional lymph node status), and M (presence or absence of distant metastasis) staging system. This systematic approach aimed to convey the extent of disease across various cancer types, providing clinicians with a practical framework to plan treatment strategies, predict prognosis, and assess outcomes. The AJCC 8th edition, effective from January 1, 2018, continues this tradition. However, certain shortcomings persist in the AJCC 8th edition, as identified through clinical experience. Specifically, challenges arise in accurately assessing depth of invasion in unique histological variants of oral squamous cell carcinoma (e.g., Oral verrucous carcinoma, Carcinoma cuniculatum, and Papillary squamous cell carcinoma) and minor salivary gland tumors. Additionally, discrepancies exist in the perception of bone invasion patterns and in reporting practices. There is also a need for staging guidelines for malignant odontogenic tumors and multifocal tumors of the oral cavity, supplemented by diagrammatic representations. Lastly, there is a call for comprehensive staging criteria for carcinomas of the ear, external auditory canal, and temporal bone. We advocate for the inclusion of these considerations in future editions of the AJCC Cancer Staging Manual.

Verrucous carcinoma on lateral tongue in association with oral submucous fibrosis: A rare case report

Oral verrucous carcinoma (VC) is a rare tumor, which a clinical variant of well differentiated oral squamous cell carcinoma characterized by exophytic growth or cauliflower like growth in appearance. It establishes in older individuals, who has habit of chronic tobacco chewing and predominance in males. Oral submucous fibrosis (OSMF) is a chronic, insidious, potentially malignant disorder associated with betel nut chewing habit. The development of oral squamous cell carcinoma (OSCC) is seen in one-third of the OSMF patients, but the development of VC is rarely seen in such patients. In the literature a very few cases of OSMF with VC are reported. Here, we present such a rare case in a 25 years old female patient with VC in conjunction with OSMF.

Recurrent Oral Verrucous Carcinoma on Left Jaw Following Post-Resection of Oral Squamous Cell Carcinoma on the Right Jaw: A Case Report and the Possible Links Which Needs Further Studies

A 72 year old patient refer to our hospital with a complain of growth on the lower left jaw since 9 months back.Patient had undergone surgical resection on the right lower jaw 10 years back with a histopathological report of squamous cell carcinoma.A biopsy was taken on the left jaw and was diagnosed as Verrucous carcinoma.

Evaluation of VEGF, BDNF, TRKB expression in oral epithelial dysplasia, oral verrucous carcinoma and oral squamous cell carcinoma and their role as prognostic indicator.

Oral squamous cell carcinoma (OSCC) is a serious health disease that can lead to a reduced quality of life or even death. It ranks sixth in terms of cancer expansion. It is one of India's primary causes of natural death. In OSCC such potentially malignant Disorders (PMDs) are precancerous lesions with such a high risk of progression. Tumor angiogenesis is a one of the basic biomarkers that may influence the proliferation of a precancerous lesion into the cancerous lesion. Tropomyosin receptor kinase B (TrkB), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF) also play important roles in carcinogenesis by promoting angiogenesis. The construction of new vessels of blood from existing vasculature is referred as angiogenesis. To get deep insights of immunohistochemistry expression of VEGF, BDNF, and TRKB in oral epithelial dysplasia (OED), verrucous carcinoma (VC), and OSCC. The study included 100 formalin-fixed paraffin-embedded tissue blocks from 20 cases of OED, 20 cases of VC, and 60 cases of OSCC [20 cases of well-differentiated oral squamous cell carcinoma (WD-OSCC), 20 cases of moderately differentiated oral squamous cell carcinoma (MD-OSCC), and 20 cases of poorly differentiated oral squamous cell carcinoma (PD-OSCC). The staining intensity and distribution of VEGF, BNDF, and TrkB were examined and statistically analyzed using analysis of variance (ANOVA), post hoc Bonferroni test, independent t-test, Pearson's Chi-square test, and Pearson's correlation coefficient test. The immunoexpression of VEGF, BDNF, and TrkB was found to be elevated in the order of OEDs, VC, and OSCC. The percentage of positive was highest in PD-OSCC, followed by MD-OSCC and WD-OSCC. Based on our findings, angiogenesis plays a significant role in tumor growth and metastasis. A substantial relationship was discovered between VEGF, BDNF, TrkB expression, and increases in vascularity throughout the transition from OEDs to VCs and OSCCs.

Oral verrucous carcinoma: a diagnostic and therapeutic challenge.

Verrucous carcinoma is a low-grade variant of squamous cell carcinoma with specific morphologic, cytokinetic and clinical features. Despite low mitotic activity and slow growth, it can infiltrate adjacent tissues in advanced stages but does not metastasize. The most frequently affected site is the oral cavity. The following article provides latest updates in the etiology, clinical presentation, diagnostics and treatment options in oral verrucous carcinoma and discusses the existing dilemmas linked to this unique malignancy. Oral verrucous carcinoma must be differentiated from conventional squamous cell carcinoma due to its less aggressive behaviour with a more favourable prognosis. Close communication between clinician and pathologist is mandatory for making a correct diagnosis. Primary surgery with negative surgical margins seems to be the most successful treatment. However, management recommendations are not uniform since they are mostly based on case reports and small retrospective case series. Prospective and pooled multi-institutional studies are therefore needed.

The stromal immunoexpression of CLIC4 may be related to the difference in the biological behavior between oral squamous cell carcinoma and oral verrucous carcinoma.

Oral squamous cell carcinoma (OSCC) has high morbidity and mortality rates while oral verrucous carcinoma (OVC), an uncommon variant of OSCC, exhibits a distinct biological behavior. CLIC4 protein plays a role in the cell cycle and apoptosis regulation and participates in the myofibroblasts transdifferentiation process, which are the main cells of the tumor stroma. This study analyzed the immunoexpression of CLIC4 and α-SMA in 20 OSCC cases and 15 OVC cases. A semiquantitative analysis of CLIC4 and α-SMA immunoexpression was performed in the parenchyma and stroma. Nuclear and cytoplasmic reactivity was analyzed separately for the CLIC4 immunostaining. The data were submitted to Pearson's chi-square and Spearman's correlation tests (p ≤ 0.05). In the CLIC4 analysis, there was a significant difference in the immunoexpression of this protein between OSCC and OVC stroma (p < 0.001). It was observed a higher expression of α-SMA in the OSCC stroma. There was a positive and significant correlation between CLIC4 and α-SMA immunoexpression in the OVC stroma (r = 0,612; p = 0,015). The decrease or absence of nuclear CLIC4 immunoexpression in the neoplastic epithelial cells and the increase of its expression in the stroma may influence the difference in biological behavior between OSCC and OVC.

Oral Verrucous Carcinoma: an Overview

Background: Verrucous carcinoma (VC) is a low-grade squamous cell carcinoma. It presents different morphologic, cytokinetic, and clinical characteristics. In advanced stages, it can infiltrate neighboring tissues despite slow growth and low mitotic activity, but it does not metastasis. The oral cavity is one of the mostly affected sites. Objective: This article reviews oral verrucous carcinoma (OVC) and offers information on its etiology, clinical appearance, diagnosis, and available treatments. Methods: Symptoms, pathogenesis, epidemiology, oral manifestations and management are reviewed. Discussion: OVC appears as a painless, white-grey, warty, exophytic mass that resembles cauliflower. It presents a strong predisposition for local invasion and a low predisposition for diffusion in neighboring structures and metastasizing. Histologically, OVC exhibits a well-differentiated squamous proliferation with a papillary or verrucous epithelial surface and clear hyperkeratosis, invading the subjacent stroma with well-defined, pushing margins. Minor atypical cells are usually seen. Conclusion: OVC is an uncommon tumor. To establish an accurate diagnosis, a comprehensive evaluation is necessary, particularly one that focuses on histology.

Proliferative Verrucous Leukoplakia with Dysplastic Changes

Proliferative verrucous leukoplakia is one of the rare premalignant white lesions with highest conversion rate to malignancy. It grows gradually and irreversibly with multifocal presentation, exophytic and verrucous appearance. This lesion has been reported resistant to all therapeutic approaches including both non-surgical and surgical. Predisposing factors include female gender in the 6th decade of life. Proliferative verrucous leukoplakia has the highest tendency to neoplastic transformation and progression to oral squamous cell carcinoma and oral verrucous carcinoma in majority of the cases. The case of proliferative verrucous lesion clinically appearing benign presented here but on histopathology proven dysplasia in a patient with the history of smoking which he stopped six years back

Postoperative Radiation Therapy in Oral Cavity Verrucous Carcinoma.

We investigate the clinicopathologic and treatment factors associated with the use of postoperative radiation therapy (PORT) and its effect on overall survival (OS) for patients with oral cavity verrucous carcinoma (VC). Retrospective cohort study. A retrospective cohort study of the National Cancer Database (NCDB) from 2006 to 2015 was performed. Multivariable logistic regression was used to identify independent predictive factors associated with the use of PORT. Cox Regression survival and propensity score analyses were used to evaluate the effect of PORT on mortality. A total of 356 adult patients with primary oral cavity VC who underwent definitive surgical resection were identified. A total of 10.7% of patients underwent definitive surgical resection followed by PORT. Variables associated with PORT included distance to the hospital per 10 miles (adjusted odds ratio [aOR], 0.81 [95% confidence interval (CI), 0.70-0.95]) and stage III-IV disease (aOR, 12.13 and 23.92, respectively). Multivariable Cox regression survival analysis indicated no evidence of survival benefit in patients undergoing PORT compared to surgery alone (adjusted hazard ratio 1.50 [0.74-3.05], P=.23). Propensity score analysis also showed no OS benefit with the use of PORT (P=.41). Variables associated with the use of PORT on multivariable analysis included closer distance to hospital and stage III-IV disease. No clear survival benefit with PORT was identified on either multivariable survival analysis or propensity score analysis. These results suggest that surgery alone with negative margins may be the optimal treatment for patients with oral cavity VC. 4 Laryngoscope, 132:1953-1961, 2022.

Association of HPV and EBV in Oral Verrucous Squamous Cell Carcinoma and Oral Verrucous Hyperplasia

Objective Oral verrucous squamous cell carcinoma or oral verrucous carcinoma (OVC) is a rare verrucous variant of oral squamous cell carcinoma (OSCC), which accounts for 2 to 12% of all oral carcinomas. Oral verrucous hyperplasia (OVH) is clinically similar to OVC and has been proposed to be a precursor lesion of OVC. Etiopathogenesis of both lesions is still inconspicuous. Oncogenic viruses such as human papillomavirus (HPV) and Epstein–Barr virus (EBV) have been reported to be associated with some cases of OSCC, and we hypothesized that it may act as a causative agent of these verrucous lesions. This study aimed to investigate frequency of HPV and EBV infections in OVC and OVH. Material and Methods Using polymerase chain reaction (PCR), a total of 35 formalin-fixed paraffin-embedded (FFPE) tissue samples, including 27 OVC samples and 8 OVH samples, were investigated for HPV and EBV infection. HeLa and B95-8 cell lines were used as positive controls of HPV and EBV PCR, respectively. Results All OVC and OVH samples show a positivity to GAPDH , whereas neither HPV nor EBV PCR products was detected in both OVC and OVH samples. Conclusions In summary, our study demonstrated that HPV and EBV are not involved in pathogenesis of OVC and OVH. Other etiologic factors contributing to OVC and OVH need to be further clarified.

Specificities of Oral Verrucous Carcinoma: Case Report and Literature Review

Introduction: Verrucous carcinoma of the oral mucosa recurs locally but does not metastasize in the absence of an invasive squamous cell carcinoma component. Clinical Observation: We report a case of an oral verrucous carcinoma in 67-year-old male patient causing bone invasion and bilateral lymph node metastasis despite the absence of a clear squamous cell carcinoma component. Discussion: Some verrucous carcinomas show dysplasia with very minor component of conventional squamous cell carcinoma. Currently, there is great challenge in diagnosing those “in between” tumor type because of the lack of standard nomenclature and studies assessing their clinical behavior.

Oral Proliferative Verrucous Leukoplakia: Progression to Malignancy and Clinical Implications. Systematic Review and Meta-Analysis

Simple SummaryProliferative verrucous leukoplakia (PVL) was recognized in 2005 by the World Health Organization as a rare subtype of true oral leukoplakia, with unknown etiology. Since its first description in 1985, several diagnostic criteria have been proposed over the years. The aim of this systematic review is to investigate the percentage of patients diagnosed with proliferative verrucous leukoplakia who progressed to oral verrucous carcinoma (OVC) or conventional oral squamous cell carcinoma (OSCC).Aim: The aim of the present systematic review was to investigate the risk of malignant transformation of proliferative verrucous leukoplakia (PVL). Materials and Methods: the search was carried out using a combination of terms (leukoplakia OR leucoplakia) AND (multifocal OR proliferative) on the following databases: PubMed, Scopus, Web of Science (WOS Core Collection), Cochrane Library, selecting only articles published since 1985 and in the English language. Demographic, disease-related, and follow-up data extracted from the studies included in the qualitative synthesis were combined. Weighted means ± standard deviations were calculated for continuous variables, while categorical variables were reported as frequencies and percentages. Dichotomous outcomes were expressed as odd ratios (ORs) with 95% confidence intervals (CIs). Odd ratios for individual studies were combined using a random-effects meta-analysis, conducted using Review Manager 5.4 Software (Cochrane Community, Oxford, England). Results: twenty-two articles were included, with a total of 699 PVL patients, undergoing a mean follow-up of 7.2 years. Sixty-six percent of patients were females, with a mean age of 70.2 years, and 33.3% were males, with a mean age of 59.6 years. Most patients were non-smokers and non-alcohol users, and the gingiva/alveolar ridge mucosa was the most involved anatomical site by both PVL appearance and malignant transformation. A total of 320 PVL patients developed oral verrucous carcinoma (OVC) or conventional oral squamous cell carcinoma (OSCC) because of malignant transformation of PVL lesions (45.8%). A statistically significant 3.8-fold higher risk of progression to conventional OSCC was found compared to OVC in PVL patients, with women being 1.7 times more likely to develop oral cancer than men, as a consequence of PVL progression. Moreover, a statistically significant higher likelihood of developing conventional OSCC in female PVL patients than in males was found. In 46.5% of patients with PVL malignant transformation, multiple carcinomas, in different oral sites, occurred during follow-up. Conclusions: PVL is an aggressive lesion, which, in a high percentage of cases (almost 50%), undergoes malignant transformation, mainly toward OSCC. The female gender is most affected, especially in the elderly, with a negative history for alcohol and tobacco consumption.

Oral verrucous carcinoma: a 24-year epidemiological study and case report

Introduction: Verrucous carcinoma is a non-metastatic variant of squamous cell carcinoma. It was first reported by Ackerman in 1948. It is a verrucous exophytic tumor and, although it is a rare lesion, it mainly affects the oral cavity, with slow growth and can be locally invasive. Objective: To report a case and present an observational and retrospective analysis of medical records containing biopsy data from patients diagnosed with oral verrucous carcinoma (OVC) in an oral diagnostic referral service for a period of 24 years. Material and methods: The following data were collected: age, sex, ethnicity, anatomical location and management. Result: Eight cases of OVC were found, all in Caucasian patients (n = 8, 100%), aged between 57 and 102 years. 62% of the injuries affected women. The most affected region was the jugal mucosa (n = 4, 50%). In addition, Smoking patients were not found. In all cases, incisional biopsy was performed and referral to the head and neck surgeon. Conclusion: Caucasian women in the sixth and seventh decades of life were the most affected by OVC. The absence of smoking patients corroborates the literature, which reports that cigarettes appear to be unrelated to this injury. The dentist's role is to recognize the disease early, diagnose it and refer it for medical treatment.

Excisional Biopsy of Verrucous Carcinoma of Tongue using Diode Laser

Oral verrucous carcinoma (OVC) is a subtle variant of oral squamous cell carcinoma with some peculiar features. It is locally invasive growth which rarely metastasizes. Verrucous carcinoma rarely affects the tongue. Herein, we report a case of excisional biopsy of a grayish-white lesion on the left lateral surface of the tongue performed with a 940-nm diode laser, which upon histopathological examination was diagnosed as OVC.

Varied Presentation of Oral Verrucous Carcinoma in a Tertiary Hospital of Dhaka City

Introduction: Ackerman’s tumor or Verrucous carcinoma is a distinguished clinic-pathological variant of squamous cell carcinoma, presenting with multiple clinical presentations. This study provides a contemporary survey of morphological presentation of oral verrucous carcinoma (OVC) in the oral cavity with site of predilection and possible etiological factors.&#x0D; Method: An observational studywas conducted from January 2014 to June 2016.A suspected patient diagnosed clinically and histologically as OVC at the Dhaka Dental College Hospital (DDCH) was enrolled in this study. Results: In this study total 15 number of patients male were 53.3% and female were 47%. The morphological presentation of the study was proliferative and verrucous, each of which comprises 40.0% of cases. The tumor's primary site was the buccal mucosa 46.67% and history ofbetel quid chewing was 46.9%.&#x0D; Conclusion: The study concluded that it is very difficult to distinguishing clinically between verrucous carcinoma and other exophytic lesions of the oral cavity. OVC presents with different morphological presentation such as proliferative and verrucous types. Buccal mucosa is the site of predilection.&#x0D; J Bangladesh Coll Phys Surg 2021; 39(2): 80-86

Verrucous carcinoma in association with oral submucous fibrosis

ABSTRACT -Oral verrucous carcinoma is a form of well differentiated squamous cell carcinoma characterized by exophytic over growth. It is slow growing and locally invasive tumor occurring in 6 th and 7 th decade of life. Smoking and chewing tobacco is found to be the most common etiological factor of verrucous carcinoma although oral leukoplakia may act as a predisposing factor. This is a rare case of oral verrucous Carcinoma seen in association with oral submucous fibrosis in a young adult patient with history of chewing gutkha and smoking.&#x0D;

Oral hybrid verrucous carcinoma: A challenging entity to clinicians

Background: Oral Verrucous Carcinoma (OVC) is defined as a verrucous variant of Squamous Cell Carcinoma (SCC) characterized by a predominantly exophytic growth of well-differentiated keratinized epithelium, with deep margins of locally aggressive invasion. The incidence of OVC is approximately 3% of all oral cancers. Its pathogenesis include chemical carcinogenesis induced by tobacco smoke, alcohol consumption, betel nut chewing and chronic inflammation. OVC occurs predominantly in people of advanced age and in males. The most common sites of involvement of the oral mucosa include the cheek mucosa, followed by the gum and tongue.

Oral verrucous carcinoma –A rare variant of ca oral cavity

Introduction: Oral verrucous carcinoma is an uncommon variant of oral squamous cell carcinoma. Demographics, clinical presentation and surgical outcomes are believed to be different from oral squamous cell carcinoma. Methodology: A single case report of verrucous carcinoma managed wide local excision of tumour with Level 1 and 2 lymph node dissection followed by Nasolabial flap reconstruction. Discussion: Verrucous carcinoma is any exophytic growth of well differentiated squamous cell carcinoma which generally presents as white warty lesion. They are slow growing with very low metastatic potential and good prognosis. Thus neck dissection and radiotherapy and chemotherapy can be avoided or limited to supraomohyoid neck dissection with close follow up.