Factor In Squamous Cell Carcinoma Research Articles

Evaluation of changes caused by HR-HPV infection in squamous cell carcinoma of the head and neck using Raman microspectroscopy in combination with multivariate statistical analysis

Abstract Introduction: Squamous cell carcinoma of the head and neck region (HNSCC), with a positive status for high oncogenic potential human papillomavirus (HR-HPV), represents a clinically distinct disease entity compared to HPV-independent cases. Patients exhibit variations in prognosis and proposed therapy regimens. A prompt and reliable diagnosis of the presence of HPV infection could optimize the treatment for these patients. Currently employed treatment methods are long-term, expensive, and lack specificity, especially when administered separately. Material and methods: The research objective of this study is to explore significant differences in the Raman spectra of biological samples taken from patients with HNSCC, facilitating the confirmation of HPV virus presence. Study groups were delineated based on histopathological diagnosis and molecular biology tests, confirming the biological activity of the virus and the presence of the HR-HPV form with a diagnosis of a specific subtype. Results: To identify high oncogenic potential human papillomavirus (HR-HPV) infection as a crucial factor in squamous cell carcinoma of the head and neck region, an effective automatic data analysis system was established, relying on Raman microspectroscopy and multivariate analysis. Our results showed clear ranges of the Raman spectrum that differentiated between HPV-associated and non-HPV-associated cancers. Conclusions: In conclusion, our experience shows a great diagnostic potential of Raman confocal microscopy with multidimensional statistical analysis. In the future, the use of this method may allow for the creation of an effective and automated HR-HPV detection system in neoplastic tissue.

Anergy as a potential risk factor for squamous cell carcinoma in an immunocompetent patient with diffuse cutaneous leishmaniasis: A case report

Despite the rarity, leishmaniasis may occur in tandem with malignancy. This co-occurrence contributes to a postulation that anergy to parasite antigens may predispose an infected patient to the development of diffuse cutaneous leishmaniasis and also increase the risk of developing squamous cell carcinoma due to decreased host immune response. We, herein, present a 63-year-old man suffering diffuse cutaneous leishmaniasis that was poorly responsive to treatment. Furthermore, the patient had several nodule-like, infiltrative, and coalescent lesions on his right face. The Montenegro skin test revealed signs of anergy and the biopsy test revealed squamous cell carcinoma (SCC) coexisting with Leishmania sp. Bodies. The patient was given a treatment with amphotericin B and later with radiation therapy, but the tumors showed a poor response to the treatment, and the patient was lost on follow-up. Our observations of the current case highlight the role of a weakening host immune response as a result of diffuse cutaneous leishmaniasis in the development of SCC. Such postulation points to and corroborates the involvement of anergy, a condition probably caused by parasite-induced suppression of the immune response, linking leishmaniasis, and skin malignancy development.

Hydrochlorothiazide and increased risk of atypical fibroxanthoma and pleomorphic dermal sarcoma.

Previous work has demonstrated that hydrochlorothiazide (HCTZ) is a risk factor for squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) due to pro-photocarcinogenic effects. Atypical fibroxanthoma (AFX) and pleomorphic sarcoma (PDS), both ultraviolet-induced cancers, display a rare but rising cutaneous tumor entity. This study aimed to evaluate if the use of HCTZ is higher in patients with AFX/PDS than in patients with SCC/BCC and subsequently may be a risk factor for AFX/PDS-development. In a retrospective study of four German skin cancer centers, AFX/PDS cases and SCC/BCC controls were sex and age matched (1:3) over a time-period of 7years (2013-2019) to evaluate the use of HCTZ, immunosuppressive medication, second malignancies, and presence of diabetes mellitus. Overall, 146 AFX/PDS and 438 controls (SCC/BCC) were included in the study. The use of HCTZ was significantly higher in patients with AFX/PDS (44.5%) compared to patients with SCC/BCC (25.3%). Additionally, the presence of diabetes mellitus was significantly higher in AFX/PDS patients. This study demonstrates a significantly higher use of HCTZ in patients with AFX/PDS compared to SCC/BCC. This result suggests that HCTZ may be a risk factor for AFX/PDS. Additionally, diabetes mellitus or its comorbidities may be associated with an increased risk for AFX/PDS.

Association of Lower Extremity Lymphedema and Nonmelanoma Skin Cancers

ObjectiveTo determine whether patients with lymphedema of a lower extremity (LE) had a greater risk of skin cancer than those without lymphedema. Patients and MethodsThis retrospective cohort study included patients with LE lymphedema examined at Mayo Clinic in Rochester, MN, USA, from January 1, 2000, through December 31, 2020. All patients with the phrase “lower extremity lymphedema” and a diagnostic code for lymphedema present in their electronic health record, as well as their age-, race-, and sex-matched controls without lymphedema, were included in the study. A Kaplan-Meier curve was constructed to examine the time to development of the first skin cancer for the lymphedema cohort and the controls. A Cox proportional hazards regression model was used to calculate hazard ratios. ResultsIn total, 4437 patients had lymphedema within the study period. Compared with the matched control group, the lymphedema group had a significantly increased risk of skin cancer. For the subset of patients with unilateral lymphedema, the lymphedematous extremity was 2.65 times as likely as the nonlymphedematous LE to have skin cancer, particularly basal cell carcinoma. ConclusionLower extremity lymphedema appears to be a risk factor for squamous cell carcinoma, basal call carcinoma, and as expected, angiosarcoma. Clinicians caring for patients with LE lymphedema should be aware of this increased risk and monitor at-risk patients accordingly.

Possibilities of skin coat color-dependent risks and risk factors of squamous cell carcinoma and deafness of domestic cats inferred via RNA-seq data.

The transcriptome data of skin cells from domestic cats with brown, orange, and white coats were analyzed using a public database to investigate the possible relationship between coat color-related gene expression and squamous cell carcinoma risk, as well as the mechanism of deafness in white cats. We found that the ratio of the expression level of genes suppressing squamous cell carcinoma to that of genes promoting squamous cell carcinoma might be considerably lower than the theoretical estimation in skin cells with orange and white coats in white-spotted cat. We also found the possibility of the frequent production of KIT lacking the first exon (d1KIT) in skin cells with white coats, and d1KIT production exhibited a substantial negative correlation with the expression of SOX10, which is essential for melanocyte formation and adjustment of hearing function. Additionally, the production of d1KIT was expected to be due to the insulating activity of the feline endogenous retrovirus 1 (FERV1) LTR in the first intron of KIT byits CTCF binding sequence repeat. These results contribute to basic veterinary research to understand the relationship between cat skin coat and disease risk, as well as the underlying mechanism.

Management of Synchronous Locally Advanced Carcinoma Oropharynx and Early Stage Carcinoma Esophagus in a Tertiary Cancer Center: A Case Report

Risk factors for squamous cell carcinomas (SCCs) of the head and neck (HN) and oesophagus are similar. As such, synchronous primary tumors in these areas are not entirely uncommon. Definitive chemoradiation (CRT) is standard care for locally advanced HNSCC and is a preferred option for inoperable oesophageal SCC. Simultaneous treatment of both primaries with CRT can present technical challenges. We report a case of synchronous oropharyngeal and oesophageal SCC primary tumors treated simultaneously with definitive chemoradiotherapy.

A prediction of late cervical lymph node metastasis by ultrasound images of tongue cancer using deep learning method

ObjectiveOccult cervical lymph node metastasis is an important prognostic factor in squamous cell carcinoma of the tongue and is related to factors such as depth of invasion and angiogenesis. The objective of this study was to evaluate the performance of deep learning for predicting occult cervical metastasis from brightness mode (B-mode) ultrasound images of early-stage tongue cancer. Methods50 patients with early-stage tongue cancer who underwent ultrasound guided partial glossectomy at the Department of Oral Surgery at Saitama Cancer Center between 2015 and 2019 were divided into two groups: those with metastasis (n = 22) and those without metastasis (n = 28). B-mode ultrasound images of each patient's tongue cancer were cropped to a 128 × 128-pixel square, and images were assigned to training or testing data in an 8:2 ratio. The training iteration generation (number of epochs) was set to 120 using Neural Network Console software (Sony Corporation), and the resulting learning model was produced. Testing data were input into the learning model to evaluate its performance in predicting metastasis. ResultsPrediction of occult cervical lymph node metastasis by deep learning using B-mode ultrasound images had 79.8 % accuracy, 78.4 % sensitivity, 80.8 % specificity, 74.4 % positive predictive value, and 84.0 % negative predictive value. ConclusionThese findings suggest that deep learning using ultrasound images is useful for predicting postoperative cervical lymph node metastasis from tongue cancer.

Decreasing Incidence of Conjunctival Squamous Cell Carcinoma in People with HIV in South Africa.

The main risk factors for squamous cell carcinoma of the conjunctiva (SCCC) are immunodeficiency and exposure to ultraviolet radiation. Little is known about the SCCC epidemiology among people with HIV (PWH) in South Africa. We used data from the South African HIV Cancer Match study, a nation-wide cohort of PWH in South Africa, created through a privacy-preserving probabilistic record linkage of HIV-related laboratory records from the National Health Laboratory Service and cancer records from the National Cancer Registry from 2004-2014. We calculated crude incidence rates, analyzed trends using Joinpoint models and estimated hazard ratios (HR) for different risk factors using Royston-Parmar flexible parametric survival models. Among 5,247,968 PWH, 1,059 incident SCCC were diagnosed for a crude overall SCCC incidence rate of 6.8/100,000 person-years. The SCCC incidence rate decreased between 2004 and 2014 with an annual percentage change of -10.9% (95% CI -13.3 to -8.3). PWH residing within latitudes 30°S-34°S had a 49% lower SCCC risk than those residing at < 25°S (adjusted HR 0.67; 95% CI 0.55-0.82). Other risk factors for SCCC were lower CD4 counts and middle-age. There was no evidence for an association of sex or settlement type with SCCC risk. An increased risk of developing SCCC was associated with lower CD4 counts and residence closer to the equator, indicative of higher ultraviolet exposure. Clinicians and PWH should be educated on known SCCC preventive measures such as maintaining high CD4 counts and protection from ultraviolet radiation through sunglasses and sunhats when outdoors.

The Prognostic Value of TTF-1/NKX2-1 in Lung Squamous Cell Carcinoma.

TTF-1/NKX2-1 is a lineage-specific transcription factor that is expressed in the thyroid gland, lung, and forehead. It functions as a key component in regulating lung morphogenesis and differentiation. It is mainly expressed in lung adenocarcinoma, while its prognostic value in non-small-cell lung cancer remains controversial. This study evaluates the prognostic value of TTF-1 in different cellular locations in lung squamous cell carcinoma (SCC) and adenocarcinoma (ADC). The expression of TTF-1 was analyzed by immunohistochemistry in 492 patients (ADC 340 and SCC 152) who had undergone surgery between June 2004 and June 2012. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Positive TTF-1 expression was 68.2% in ADC (located in the nucleus) and 29.6% in SCC (cytoplasm staining). The presence of TTF-1 was associated with better OS in SCC and ADC (P=0.000 and P=0.003, respectively). In SCC, an increased level of TTF-1 was associated with a longer disease-free survival (DFS). Positive TTF-1 expression was an independent favorable prognostic factor in SCC (P=0.020, HR: 2.789, 95%CI: 1.172-6.637) and ADC (P=0.025, HR: 1.680, 95%CI: 1.069-2.641). TTF-1 was largely located in the nucleus of ADC, while it always accumulated in the cytoplasm of SCC. The higher level of TTF-1 in the different subcellular locations of ADC and SCC was an independent, favorable prognostic factor, respectively. Increased TTF-1 in the cytoplasm of SCC was associated with a longer OS and DFS.

Oncological outcomes and prognostic factors of squamous cell carcinoma of the upper gingiva and hard palate: a retrospective study.

Despite sharing the same staging system as oral cavity cancers, upper gingiva and hard palate (UGHP) squamous cell carcinoma (SCC) have several features that make them a different entity. We aimed to analyze oncological outcomes and adverse prognostic factors of UGHP SCC, and assess an alternate T classification specific to UGHP SCC. Retrospective bicentric study including all patients treated by surgery for a UGHP SCC between 2006 and 2021. We included 123 patients with a median age of 75years. After a median follow-up of 45months, the 5-year overall survival (OS), disease-free survival (DFS) and local control (LC) were 57.3%, 52.7% and 74.7%, respectively. Perineural invasion, tumor size, bone invasion, pT classification and pN classification were statistically associated with poorer OS, DFS and LC on univariate analysis. On multivariable analysis, the following variable were statistically associated with a poorer OS: past history of HN radiotherapy (p = 0.018), age > 70years (p = 0.005), perineural invasions (p = 0.019) and bone invasion (p = 0.030). Median survivals after isolated local recurrence were 17.7 and 3months in case of surgical and non-surgical treatment, respectively (p = 0.066). The alternate classification allowed better patient distribution among T-categories, however without improving prognostication. There is a broad variety of clinical and pathological factors influencing prognosis of SCC of the UGHP. A comprehensive knowledge of their prognostic factors may pave the way towards a specific and more appropriate classification for these tumors.

The Influence of the Oral Microbiome on Oral Cancer: A Literature Review and a New Approach.

In our recent article (Smędra et al.: Oral form of auto-brewery syndrome. J Forensic Leg Med. 2022; 87: 102333), we showed that alcohol production can occur in the oral cavity (oral auto-brewery syndrome) due to a disruption in the microbiota (dysbiosis). An intermediate step on the path leading to the formation of alcohol is acetaldehyde. Typically, acetic aldehyde is transformed into acetate particles inside the human body via acetaldehyde dehydrogenase. Unfortunately, acetaldehyde dehydrogenase activity is low in the oral cavity, and acetaldehyde remains there for a long time. Since acetaldehyde is a recognised risk factor for squamous cell carcinoma arising from the oral cavity, we decided to analyse the relationship linking the oral microbiome, alcohol, and oral cancer using the narrative review method, based on browsing articles in the PubMed database. In conclusion, enough evidence supports the speculation that oral alcohol metabolism must be assessed as an independent carcinogenic risk. We also hypothesise that dysbiosis and the production of acetaldehyde from non-alcoholic food and drinks should be treated as a new factor for the development of cancer.

Cancer of tongue-our fixed entity

Background: Oral cancer ranks the top three of all cancers in India. This study aimed to determine etiologic factors for squamous cell carcinoma (SCC) of the tongue and its management. Methods: This longitudinal retrospective study was conducted with 30 patients of biopsy- proven SCC of tongue diagnosed in our hospital between the years of 2010-2022. Medical records, including history of abuse of alcohol, betel nuts, tobacco products and human papillomavirus (HPV) infection were recorded. The patients details including tumour size, location, node metastasis, grade, disease recurrence, other primary cancers, delay time until diagnosis, therapy course were noted. Patients were analyzed based on etiology and management undertaken. Results: Among 30 patients with SCC tongue, 25 (83.33%) were males, 5 (16.66%) were females. Smoking was significantly higher in males (20 patients), in those 5 alcoholics. Chronic mechanical trauma was observed in 5 patients. HPV infection was observed in 2 males, 3 females had betel nut chewing habit and use of smokeless tobacco. Among 30 cases alcohol abuse, smoking, chronic mechanical traumas, HPV infection and betel nut chewing appeared as significant etiologic factors of which smoking was the most common etiology (50%). Surgical excision with neck dissection followed by radiotherapy was treatment undertaken in our study patients based on SCC tongue stage. Conclusions: our study concluded that smoking is the most common etiology of SCC tongue, the definitive treatment is surgery combined with radiotherapy based on TNM staging.

Prognostic impact of lymphovascular and perineural invasion in squamous cell carcinoma of the tongue

This study aimed to investigate the prognostic impact of lymphovascular and perineural invasions in patients with squamous cell carcinoma of the tongue who received surgery-based treatment at our institution between January 2013 and December 2020. Patients were divided into four groups based on the presence of perineural (P−/P +) and lymphovascular invasions (V−/V +): P–V−, P–V + , P + V−, and P + V + . Log-rank and Cox proportional hazard models were used to evaluate the association between perineural /lymphovascular invasion and overall survival (OS). Altogether, 127 patients were included, and 95 (74.8%), 8 (6.3%), 18 (14.2%), and 6 (4.7%) cases were classified as P–V−, P–V + , P + V−, and P + V + , respectively. Pathologic N stage (pN stage), tumor stage, histological grade, lymphovascular invasion, perineural invasion, and postoperative radiotherapy were significantly associated with OS (p < 0.05). OS was significantly different among the four groups (p < 0.05). Significant between-group differences in OS were detected for node-positive (p < 0.05) and stage III–IV (p < 0.05) cases. OS was the worst in the P + V + group. Lymphovascular and perineural invasions are independent negative prognostic factors for squamous cell carcinoma of the tongue. Patients with lymphovascular and/or perineural invasion may have significantly poorer overall survival than those without neurovascular involvement.

Micrometastasis detection using modified papanicolaou stain in nodal tissues of oral squamous cell carcinoma - A histological study.

Cervical lymph node metastasis is the most important prognostic factor in Squamous Cell Carcinoma of Head and Neck (SCCHN). Detection and evaluation of micro-metastasis forms the basis for diagnosis, staging, treatment options and prognosis. Lymph node prognostic factors are extremely important for the survival and recurrence in the patient. Assessing lymph node metastasis in the absence of clinical enlargement is challenging. To evaluate micrometastasis and individual tumor cells (ITC) in regional lymph nodes of oral squamous cell carcinoma (OSCC) by modified papanicolaou (PAP) stain and re-evaluate the tumor staging. The retrospective study was executed at MS Ramaiah University of Applied Sciences. The current study constituted a total of 40 lymph nodes from OSCC patients, metastatic (n=20) and non-metastatic lymph nodes (n=20). All sections were stained with H & E followed by modified PAP stain. Modified PAP was used for identification of micrometastasis deposits. The Chi square test was employed to analyze significance. Modified PAP stain proved to be more accurate (p = 0.006) than H and E stain in detecting micrometastasis which accounted for 15% of non-metastatic lymph node sections used in our study. Special stain like modified PAP stain is valuable and sensitive in detecting micro-metastasis over H and E stain. Detection of micrometastasis in OSCC patients is advantageous for the patient as it influences staging, it modifies the treatment plan in terms of both radiotherapy and chemotherapy.

PREDICTORS OF LYMPHNODE METASTASIS IN SQAUMOUS CELL CARCINOMA TONGUE

Back Ground:The most important prognostic factor for squamous cell carcinoma (SCC) of oral is the status of cervical lymph nodes. Cure rates drop by 50% with involvement of regional lymph nodes. Cure rates drop by 50% with involvement of regional lymph nodes.The rate of occult metastasis in clinically negative neck for oral tongue cancers ranges from &lt;20% to &gt;30% depending on many predictors. Methods:The relationship clinical and histologic features of the primary tumor of tongue and metastasis to neck nodes was investigated in 90 patients. Results:Histopathologic features of primary tumor showed significant differences in relation to metastasis to neck nodes Conclusion:Tumor stage ,grade. vascular and perineural invasion,morphology ,tumor thickness are important predictors in predicting metastasis to neck nodes.

Evaluation of the Cellular Dissociation Grading, Based on Tumor Budding and Cell Nest Size, in Squamous Cell Carcinoma of the Penis.

Simple SummaryThe pathological status of regional lymph nodes (pN) is the most important predictor of survival in patients with invasive squamous cell carcinoma of the penis. However, staging strategies have limited prediction, which results in false-negative findings or unnecessary lymphadenectomies. Therefore, additional criteria should be identified to improve the prediction of lymph node involvement. The “Cellular Dissociation Grade” (CDG) is based on tumor cell budding and cell nest size. Many studies have examined the CDG in squamous cell carcinomas of other organs such as the lungs, oral cavity, pharynx, larynx, cervix and esophagus. In this study, the CDG was examined in 109 cases of invasive penile squamous cell carcinoma that were treated at the University Medicine Rostock between 2014 and 2022. Furthermore, its correlation with the pathologic status of regional lymph nodes (pN) as the main prognostic factor was verified. Finally, cellular dissociation grading was compared with classic WHO grading. The results showed that pN in penile squamous cell carcinoma showed a highly significant association with the CDG and no statistically significant association with WHO grading. These results support the notion that cellular dissociation grading is an important prognostic factor for squamous cell carcinoma.

Sarcopenia Is an Independent Prognostic Factor for Squamous Cell Carcinoma of the Cervix Treated With Concurrent Chemoradiotherapy.

To investigate sarcopenia as a predictor of prognosis before concurrent chemoradiotherapy (CCRT) in patients with squamous cell carcinoma (SCC) of the cervix using the new psoas muscle index (PMI) cutoff value for sarcopenia in Japanese women. We included 134 patients with SCC of the cervix treated with CCRT. CT images were taken within one month before treatment. Measurements of PM and skeletal muscle (SM) area were taken at the L3 level using a CT image analysis system (Synapse Vincent). Whole-pelvic external beam radiotherapy (EBRT) with 50 Gy was performed. High-dose-rate intracavitary brachytherapy and boost EBRT doses were administered. The patients received 40 mg/m2 of cisplatin weekly during CCRT. Kaplan-Meier analysis and the log-rank test were used to compare survival rates. The five-year overall survival (OS) and five-year progression-free survival of all 134 patients were 86.1% and 77.3%, respectively. Univariate analysis revealed that only PMI had a significant association with OS (PMI <3.92 cm2/m2 in the sarcopenia group vs. PMI ≥3.92 cm2/m2 in the non-sarcopenia group, p=0.0112), with no significant differences in age, advanced stage of disease, tumor size, lymph node enlargement, serum SCC, or SMI. Multivariate analysis revealed that PMI is the only independent prognostic factor for OS, but none of the factors were found to have a significant association with PFS. PMI as an indicator of sarcopenia was found to be an independent prognostic factor for patients with SCC of the cervix who underwent CCRT.

The Immunohistochemical Assessment of Neoangiogenesis Factors in Squamous Cell Carcinomas and Their Precursors in the Skin.

Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer. Well-limited forms can be easily treated with excision, but locally advanced cancers can, unfortunately, progress to metastasis. However, it is difficult to establish the prognosis for cutaneous squamous cell carcinoma and its potential to metastasize. Therefore, this study aimed to evaluate neoangiogenesis in cSCC, as it plays a major role in the dissemination of neoplasia. A literature review was performed on selected neoangiogenic factors (VEGF, ANG1/2, Notch1, CD31/34/105, EGF, etc.). Most of them, including VEGF, EGFR, and CD105, had more elevated levels in the advanced stages of the lesion. The same is true for Notch1, p53, and TGFβ, which are the most frequently mutated tumor suppressors in this type of skin cancer. In addition, the inhibition of some of these markers, using Ang1 analogs, inhibitors of EGFR, TRAF6, or combined inhibitors of EGFR and IGF-IR, may lead to a decrease in tumor size. In conclusion, this literature review identified diagnostic and prognostic markers, as well as possible factors that can be used for the targeted therapy of spinaliomas.

VEGF expression in cetuximab resistance development in patients with squamous cell carcinoma of the tongue and oral mucosa.

e18072 Background: Clinical course and aggressiveness of a tumor, as well as the subtle mechanisms of its pathogenesis are related to vascularization, which in turn is determined by the ability of transformed cells to synthesize a wide range of biologically active substances. Among modern approaches to cancer treatment, special attention is paid to anti-EGFR agents reducing tumor vascularization. The purpose of this study was to analyze VEGF expression in tumor vessels in patients with squamous cell carcinoma of the tongue and oral mucosa developing cetuximab resistance. Methods: The study included 45 patients with squamous cell carcinoma of the tongue and oral mucosa T3-4N0-1M0. The patients were divided into 3 groups: group 1 – all patients before treatment; group 2 – patients after standard chemotherapy with cisplatin and fluorouracil; group 3 – patients after chemotherapy in combination with targeted therapy with cetuximab. Immunohistochemical study was performed on sections from paraffin blocks of tumors using monoclonal murine anti-VEGF antibodies (clone VG1, Thermo Scientific) diluted 1:150. The Reveal Polyvalent HRP-DAB Detection System was used. The significance of differences was assessed using the Mann Whitney and Wilcoxon tests calculated using the STATISTICA 10.0 program (StatSoftInc., USA). Results: Changes in the density of vessels stained with the VEGF marker were studied in tumor cells of patients in all groups. Patients in group 1 had from 3 to 10 vessels in one field of view; in group 2 – from 2 to 6 vessels in 70% of cases (21) and up to 15 vessels in 30% of cases (9); in group 3 – only solitary vessels. The average numbers of microvessels stained with the VEGF marker per field of view were 6.5±1.52; 4.5±1.71; 1.0±0.28, respectively. Quantification of intratumoral microvascular density showed that the minimum number of microvasculature vessels in the field of view was observed in patients who received chemotherapy and targeted therapy with cetuximab. The value was 5 times lower compared to initial values, and 4 times lower than in patients who received only standard chemotherapy (the Mann Whitney test, p &lt; 0.05). The statistical analysis according to the Wilcoxon test on the effect of targeted therapy (comparison between groups 2 and 3) revealed a statistically significant effect of cetuximab for this marker (p = 0.028). Conclusions: Immunohistochemical analysis of the VEGF neoangiogenesis factor in squamous cell carcinoma of the tongue and oral mucosa confirmed the effectiveness of targeted therapy with cetuximab.

Tumor budding activity is an independent prognostic factor in squamous cell carcinoma of the vulva

Tumor budding activity (TBA) is recognized as a potential prognostic factor in carcinomas from several anatomic sites. This study evaluates the prognostic value of TBA in a cohort of squamous cell carcinoma of the vulva (VSCC). TBA, defined as clusters of <5 tumor cells that are detached from the main tumor and that infiltrate into surrounding stroma, was assessed in 82 cases of surgically excised VSCC and correlated with patient outcomes. All cases were classified into one of 3 groups: no TBA, low TBA (1-14 foci), and high TBA (≥15 foci). Twenty-three (29.1%), 37 (45.1%), and 22 (26.8%) cases showed no, low, and high TBA, respectively. High TBA was associated with reduced overall survival (OS) on multivariate analysis independent of FIGO stage, human papillomavirus (HPV) status, and p53 status. The majority of tumors with high TBA displayed a p53 mutant staining pattern (77.3%, 17 of 22). The 17 patients whose tumors displayed a p53 mutant/high TBA profile had worse outcomes when compared with 15 patients whose tumors showed a p53 mutant/no TBA or p53 mutant/low TBA profile (mean OS 37.5 versus 63.3 months, respectively, P=.002). High TBA was observed in only 5 of 47 HPV-associated cases, and this subsetalso seemed to display a worse patient outcome as compared with the rest of the HPV-associated cohort (OS 16.8 versus 142.8 months, P<.0001). In summary, these findings indicate that TBA is an independent prognostic indicator in VSCC patients, and that high TBA is associated with worse clinical outcomes.