Search Results (236)

Background/Objectives: Malignant adrenal tumors comprise both primary adrenal neoplasms and metastatic lesions, with the latter being significantly more common. Squamous cell carcinoma (SCC) of the larynx is a prevalent head and neck cancer that typically spreads to the cervical lymph nodes, with distant metastases being rare. Among such metastases, adrenal gland involvement is particularly uncommon, presenting unique diagnostic and therapeutic challenges. The study aimed to explore the progression, diagnostic process, and therapeutic management of a rare case of SCC of the larynx metastasizing to the adrenal gland, highlighting the role of advanced diagnostic imaging and a multidisciplinary approach in patient care. Methodology: A 66-year-old male with grade 3 SCC of the larynx underwent total laryngectomy, selective cervical lymphadenectomy, and radiotherapy with a dose of 70 Gy. Chemotherapy was discontinued due to hematological complications. Post-treatment monitoring included CT and PET-CT imaging, leading to the detection of a large adrenal mass. Surgical biopsy confirmed metastatic SCC in the adrenal gland, as resection was not feasible due to extensive invasion. Diagnostic imaging and histopathological examination were complemented by biochemical evaluations to assess hormonal activity. Results: The adrenal mass was identified as a metastasis from the laryngeal SCC. Imaging studies provided detailed insights into the lesion’s size, metabolic activity, and non-functional status. Despite comprehensive efforts, the tumor was deemed unresectable, highlighting the aggressive nature of the disease and the limitations of current therapeutic modalities. Conclusions: This rare case emphasizes the importance of early detection, advanced imaging techniques, and interdisciplinary collaboration in managing complex metastatic presentations. It underscores the critical need for further research into systemic treatments, such as immunotherapy, and the development of standardized protocols for rare metastatic patterns. The study contributes to the growing body of literature on the management of uncommon cancer metastases, advocating for individualized patient care and innovation in treatment strategies. Full article

(1) Background: Oral tongue squamous cell carcinoma (OTSCC) is a prevalent malignancy with high loco-regional recurrence. Advanced imaging biomarkers are critical for stratifying patients at a high risk of recurrence. This study aimed to develop MRI-based radiomic models to predict loco-regional recurrence in OTSCC patients undergoing surgery. (2) Methods: We retrospectively selected 92 patients with OTSCC who underwent MRI, followed by surgery and cervical lymphadenectomy. A total of 31 patients suffered from a loco-regional recurrence. Radiomic features were extracted from preoperative post-contrast high-resolution MRI and integrated with clinical and pathological data to develop predictive models, including radiomic-only and combined radiomic–clinical approaches, trained and validated with stratified data splitting. (3) Results: Textural features, such as those derived from the Gray-Level Size-Zone Matrix, Gray-Level Dependence Matrix, and Gray-Level Run-Length Matrix, showed significant associations with recurrence. The radiomic-only model achieved an accuracy of 0.79 (95% confidence interval: 0.69, 0.87) and 0.74 (95% CI: 0.54, 0.89) in the training and validation set, respectively. Combined radiomic and clinical models, incorporating features like the pathological depth of invasion and lymph node status, provided comparable diagnostic performances. (4) Conclusions: MRI-based radiomic models demonstrated the potential for predicting loco-regional recurrence, highlighting their increasingly important role in advancing precision oncology for OTSCC. Full article

Background: Sparc/osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1) is an oncogene that promotes tumor formation and progression in certain types of cancer and is associated with poor survival rates. However, there is limited information on the importance of SPOCK1 in gynecological cancers in the literature. The aim of this study was to explore the role of SPOCK1 in ovarian serous cystadenocarcinoma (OV), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), and uterine corpus endometrial carcinomas (UCEC). Methods: The data used in this study were obtained from the GEPIA2, TCGA, Kaplan–Meier Plotter, GeneMANIA, UALCAN, cBioPortal, and TIMER databases. Overall survival (OS) and relapse-free survival (RFS) rates were evaluated by Kaplan–Meier survival analysis. Spearman’s rho and statistical significance values were obtained for the correlation between SPOCK1 expression and tumor infiltration by different immune cells. Results: Lower SPOCK1 gene expression was observed in CESC and UCEC compared to normal tissue (p < 0.05), but the OV did not differ significantly (p > 0.05). In OV, SPOCK1 gene expression was solely linked to age; in CESC, it was linked to age, stage, weight, and histology; and in UCEC, it was linked to age, stage, weight, and menopausal status. Conclusions:SPOCK1 gene expression in UCEC showed weak positive correlations with CD8+ T cells and weak negative correlations with CD4+ T cells. SPOCK1 may be a potential prognostic and therapeutic target for gynecological cancers. Full article

Hypoxia, a common feature in many malignancies, is particularly prominent in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). Investigating the mechanisms underlying hypoxia is essential for understanding the heterogeneity of CESC and developing personalized therapeutic regimens. Firstly, the CESC-specific hypoxia gene sets shared between single-cell RNA sequencing (scRNA-seq) and bulk data were identified through Weighted Gene Correlation Network Analysis (WGCNA)and FindMarkers analyses. A CESC-specific hypoxia-related score (CSHRS) risk model was constructed using the least absolute shrinkage and selection operator (LASSO)and Cox regression analyses based on these genes. The prognostic differences were analyzed in terms of immune infiltration, mutations, and drug resistance. Finally, a nomogram model was constructed by integrating clinicopathological features to facilitate precision treatment for CESC. This study constructed a CSHRS risk model that divides patients into two groups, and this model can comprehensively evaluate the tumor microenvironment characteristics of CESC, provide accurate prognostic predictions, and offer rational treatment options for patients. Full article

Background: Cervical cancer is the most important cancer type found in women throughout the world. Numerous research studies are being performed to investigate the effectiveness of different strategies for the imaging and treatment of locally advanced cervical cancer, which are showing favorable outcomes. Brachytherapy is characterized by the application of very high radiation doses to target tumor cells with the least exposure to normal tissues. Methods: In the present case study, we report a 43-year-old female patient suffering from cervical cancer belonging to urban origin, with no personal pathological history, who presented herself to the gynecology department of the Bihor County Emergency Clinical hospital with vaginal bleeding. The histopathological examination of the cervix showed squamous cell carcinoma. The treatment was performed with neoadjuvant chemotherapy and concurrent chemoradiotherapy. Results: According to the clinical and histopathological examination, a diagnosis of non-keratinizing squamous carcinoma of the uterine cervix at FIGO stage III C1 was established. Radio-chemotherapy was performed, as well as periodic imaging assessments with a CT of the chest, pelvis, and abdomen, without local and distant relapse. FDG PET imaging was performed for the management and follow-up of cervical cancer by retrieving the SUVmax value. Conclusions: The post-therapeutic complications are represented by the vaginal stenosis installed 6 months after the end of the radiotherapeutic treatment. Full article

Background/Objectives: Cervical mesonephric adenocarcinomas (MNACs) are among the rarest neoplasms of the female genital tract. Unlike the majority of cervical cancers, which are predominantly squamous in origin and strongly associated with HPV seropositivity, MNACs are distinct in both histology and pathophysiology. Despite their unique characteristics, MNACs have historically been managed in parallel with squamous cell carcinomas, resulting in a lack of optimised, evidence-based treatment protocols. In this systematic review, we aim to evaluate the current management strategies for MNACs and their associated clinical outcomes. Additionally, we critically appraise existing surgical and adjuvant therapies and propose embryologically oriented surgical techniques to achieve optimal tumour resection. Methods: We performed a systematic search across the MEDLINE, CENTRAL, EMBASE, and ClinicalTrials.gov databases from 1960 to June 2024. The search strategy employed a combination of keywords and MeSH terms, including “Uterine Cervical Neoplasms” [MeSH], “mesonephric tumour”, “mesonephric neoplasm”, and “mesonephric cancer”. All relevant publications, including case reports and case series, were considered. Results: A total of 49 publications were finally included in the analysis, involving a thorough description of 91 MNAC cases. Most patients had stage I disease (70.8%) (n = 51). Hysterectomy was performed in 77 patients. The median follow-up was 29 months (range 1–199 months). Disease recurrence was observed in 35.2% (n = 25) of the cases, with the median disease-free survival (DFS) being 24 months (range 1–199). At the follow-up, 64.8% (n = 46) of patients remained in remission irrespective of the treatment modality, while 27.4% (n = 20) died due to disease progression. Conclusions: Mesonephric neoplasms of the uterine cervix are rare and clinically aggressive cancers that signify poor prognosis. Accurate identification and effective management can be challenging due to their particular anatomic and immunohistochemical characteristics. Therefore, a more tailored embryological-based approach should be considered for an optimal oncologic outcome. Full article

Background: Traditional imaging techniques have limited efficacy in detecting occult cervical lymph node (LN) metastases in head and neck squamous cell carcinoma (HNSCC). Positron emission tomography/computed tomography (PET-CT) has demonstrated potential for assessing HNSCC, but the literature on its efficacy for detecting cervical LN metastases is scarce and exhibits varied outcomes, hindering comparisons. Aim: To compare the efficacy of CT, MRI, PET-CT, and US for detecting LN metastasis in HNSCC with clinically negative neck lymph nodes. Methods: A systematic search was performed using Web of Science, PubMed, Scopus, Embase, and Cochrane databases. Studies comparing CT, MRI, PET-CT, or US to detect cervical metastases in HNSCC were identified. The quality of the studies was assessed using the QUADAS-2 instrument. The positive likelihood ratios (+LR) and negative likelihood ratios (−LR), sensitivity (SEN), specificity (SPE), and diagnostic odds ratio (DOR), with 95% confidence intervals (C.I.), were calculated. Analysis was stratified according to lymph node and patient basis. Results: Fifty-seven studies yielded 3791 patients. At the patient level, PET-CT exhibited the highest diagnostic performance, with a SEN of 74.5% (95% C.I.: 65.4–81.8%) and SPE of 83.6% (95% C.I.: 77.2–88.5%). PET-CT also demonstrated the highest +LR of 4.303 (95% C.I.: 3.082–6.008) and the lowest −LR of 0.249 (95% C.I.: 0.168–0.370), resulting in the highest DOR of 15.487 (95% C.I.: 8.973–26.730). In the evaluation of diagnostic parameters for various imaging modalities on node-based analysis results, MRI exhibited the highest SEN at 77.4%, and PET demonstrated the highest SPE at 96.6% (95% C.I.: 94.4–98%). PET-CT achieved the highest DOR at 24.353 (95% C.I.: 10.949–54.166). Conclusions: PET-CT outperformed other imaging modalities across the majority of studied metrics concerning LN metastasis detection in HNSCC. Full article

Background and Objectives: This study primarily aims to evaluate the preoperative staging effectiveness of PET-CT in early-stage cervical cancer, particularly, its ability to detect primary tumors and micrometastases. Materials and Methods: In this retrospective study, cervical cancer patients who had undergone preoperative 18F FDG PET-CT scans and were treated at the Department of Gynecology, Institute of Oncology, Vojvodina, in Sremska Kamenica, during the period from 2016 to 2020 were analyzed. Results: The study included 62 patients (mean age, 49.3 ± 9.6 years). Squamous cell carcinoma was the predominant histological type (95.2%), with G2 differentiation (82.3%) and FIGO stage Ib1 (80.6%) being the most common. Assessed by 18F FDG PET-CT, the mean tumor size was 26.4 ± 10.8 mm, which is slightly lower than the 26.9 mm measured during clinical examination (p = 0.784), with a significant (r = 0.678, p < 0.001) correlation between these methods. 18F FDG PET-CT demonstrated an overall accuracy of 88.7% for identifying primary tumors, with a sensitivity of 86.8%, specificity of 100.0%, PPV of 100.0%, and NPV of 56.2%. An intraoperative examination showed identical overall accuracy but higher sensitivity (98.1%) and lower specificity (33.3%). For 18F FDG PET-CT, the level of agreement with the histopathological examination was good (Kappa 0.656), while for the intraoperative examination, it was moderate (Kappa 0.409). Regarding the lymph node assessment, 18F FDG PET-CT’s accuracy was 82.2%, with a sensitivity of 53.8% and a specificity of 89.8%. The intraoperative examination showed lower accuracy (66.1%) but higher sensitivity (76.9%). The 18F FDG PET-CT Kappa value indicated moderate agreement (0.449), while the intraoperative examination showed poor agreement (0.282). Conclusions: In conclusion, significant effectiveness is shown by 18F FDG PET-CT for preoperative staging of early-stage cervical cancer, offering superior accuracy in detecting primary tumors and micrometastases, particularly in predicting lymph node metastases, thereby enhancing diagnostic accuracy and informing treatment decisions. Full article

Background and Objectives: Despite the distinct entity of both p16-positive and p16-negative squamous cell carcinoma unknown primary in the head and neck (HNSCCUP), the diagnostic workup did not differ. The aim of the study was to determine the effectiveness of palatine tonsillectomy in the identification of primary tumours in two groups of p16-positive and p16-negative HNSCCUP. Materials and Methods: Patients with HNSCCUP managed in two tertiary care referral centres from 1 January 2014 to 31 December 2020 were analysed retrospectively. Results: Sixty-six patients with HNSCCUP diagnosis were included consecutively. HPV status of metastatic cervical lymph nodes using immunohistochemistry with p16 protein was available for all patients. The proportion of both p16-positive and p16-negative groups was not significantly different (p = 0.242). Of the 39 patients who underwent palatine tonsillectomy, tonsillar cancers were revealed histologically in 6 (15.4%) patients, and all these patients were p16-positive. No primary tonsillar tumour was found in the p16-negative group (0 of 17). The primary tumour identification rate in p16-positive HNSCCUP patients using palatine tonsillectomy was 27% (6 of 22). Conclusions: The diagnostic workup of HNSCCUP should be guided according to HPV/p16 status. Palatine tonsillectomy is a useful procedure in identifying primary cancer in p16-positive SCCUP patients, however, its effectiveness in p16-negative patients is debatable. Full article

Anal Squamous Cell Carcinoma (SCCA) is a rare Human Papillomavirus type 16 (HPV16)-associated carcinoma whose pathogenesis is still poorly understood. Recent studies based on biopsy and Next Generation Sequencing (NGS) approaches have linked the viral episomal status to aggressive SCCA phenotypes, suggesting a potential role of the 16E5 oncoprotein in tumor development. Our previous findings indicated that 16E5 induces Fibroblast Growth Factor Receptor 2 (FGFR2) isoform switching, aberrant mesenchymal FGFR2c expression, Epithelial Mesenchymal Transition (EMT), and cell invasion in various in vitro human keratinocyte models, as well as in the in vivo context of cervical Low-grade Squamous Intraepithelial Lesions (LSILs). To further explore the role of 16E5 in epithelial carcinogenesis, this study aims to investigate the molecular profile in HPV-related anal lesions. The results showed a significant positive correlation between 16E5 and FGFR2c, as well as 16E5 or FGFR2c and key EMT-related transcription factors, particularly in the group of HPV16 positive anal samples not containing without high grade lesions. Additionally, by coupling the molecular analysis with an interactome investigation, we hypothesized a potential functional interplay between the Ca²⁺ channel Transient Receptor Potential Ankyrin 1 (TRPA1) and FGFR2c, mediated by 16E5 during the establishment of the oncogenic signaling. These findings will help to elucidate the actual relevance of 16E5 in the early progression of anal lesions and contribute to determine its potential as target for future preventive approaches for HPV16-positive SCCA. Full article

Background: CD59, a GPI-anchored membrane protein, protects cancer cells from complement-dependent cytotoxicity (CDC) by inhibiting the formation of the membrane attack complex (MAC). It has been demonstrated to be overexpressed in most solid tumors, where it facilitates tumor cell escape from complement surveillance. The role of CD59 in cancer growth and interactions between CD59 and immune cells that modulate immune evasion has not been well explored. Methods: Using cancer patient database from The Cancer Genome Atlas (TCGA) and other public databases, we analyzed CD59 expression, its prognostic significance, and its association with immune cell infiltration in the tumor microenvironment, identifying associated genomic and functional networks and validating findings with invitro cell-line experimental data. Results: This article describes the abundant expression of CD59 in multiple tumors such as cervical squamous cell carcinoma (CESC), kidney renal cell carcinoma (KIRC), glioblastoma multiforme (GBM), head and neck squamous cell carcinoma (HNSC), and stomach adenocarcinoma (STAD), as well as in pan-cancer, using The Cancer Genome Atlas (TCGA) database and confirmed using multiple cancer cell lines. The expression of CD59 significantly alters the overall survival (OS) of patients with multiple malignancies such as CESC, GBM, HNSC, and STAD. Further, the correlation between CD59 and Treg and/or MDSC in the tumor microenvironment (TME) has shown to be strongly associated with poor outcomes in CESC, GBM, HNSC, and STAD as these tumors express high FOXP3 compared to KIRC. Moreover, unfavorable outcomes were strongly associated with the expression of CD59 and M2 tumor-associated macrophage infiltration in the TME via the IL10/pSTAT3 pathway in CESC and GBM but not in KIRC. In addition, TGFβ1-dominant cancers such as CESC, GBM, and HNSC showed a high correlation between CD59 and TGFβ1, leading to suppression of cytotoxic T cell activity. Conclusion: Overall, the correlation between CD59 and immune cells predicts its prognosis as unfavorable in CESC, GBM, HNSC, and STAD while being favorable in KIRC. Full article

Background/objectives: Pathological ultrastaging, an essential part of sentinel lymph node (SLN) mapping, involves serial sectioning and immunohistochemical (IHC) staining in order to reliably detect clinically relevant metastases. However, ultrastaging is labor-intensive, time-consuming, and costly. Deep learning algorithms offer a potential solution by assisting pathologists in efficiently assessing serial sections for metastases, reducing workload and costs while enhancing accuracy. This proof-of-principle study evaluated the effectiveness of a deep learning algorithm for SLN metastasis detection in early-stage cervical cancer. Methods: We retrospectively analyzed whole slide images (WSIs) of hematoxylin and eosin (H&E)-stained SLNs from early-stage cervical cancer patients diagnosed with an SLN metastasis with either H&E or IHC. A CE-IVD certified commercially available deep learning algorithm, initially developed for detection of breast and colon cancer lymph node metastases, was employed off-label to assess its sensitivity in cervical cancer. Results: This study included 21 patients with early-stage cervical cancer, comprising 15 with squamous cell carcinoma, five with adenocarcinoma, and one with clear cell carcinoma. Among these patients, 10 had macrometastases and 11 had micrometastases in at least one SLN. The algorithm was applied to evaluate H&E WSIs of 47 SLN specimens, including 22 that were negative for metastasis, 13 with macrometastases, and 12 with micrometastases in the H&E slides. The algorithm detected all H&E macro- and micrometastases with 100% sensitivity. Conclusions: This proof-of-principle study demonstrated high sensitivity of a deep learning algorithm for detection of clinically relevant SLN metastasis in early-stage cervical cancer, despite being originally developed for adenocarcinomas of the breast and colon. Our findings highlight the potential of leveraging an existing algorithm for use in cervical cancer, warranting further prospective validation in a larger population. Full article

Background: Human papilloma virus (HPV) infection is responsible for 4.5% of cancers worldwide, i.e., for around 630,000 new cases per year. Around 38,000 cases per year of HPV-related cancers arise in the head and neck region, of which 21,000 cases are oropharyngeal squamous cell carcinomas (OPSCCs), with an increasing frequency in high-income countries. In our work, we aimed to collect the available evidence about the awareness of the relation between HPV infection and head and neck cancer among patients and practitioners. Methods: This review was based on all available prospective and retrospective studies, case reports, and review articles published up to May 2024 in PubMed. The search keywords used included “human papilloma virus” plus “head and neck cancer”, “awareness”, “infection”, “vaccination”, “awareness in patients and practitioners”, “oropharyngeal squamous cell carcinoma”, “HPV16-18”, “HPV awareness”, “cervical cancer”. Results: In the U.S.A., with more than 150.00 participants interviewed through different studies, the identification of HPV infection as a risk factor for head and neck cancer (HNC) was made by only 12–39% of the participants. Similar conclusions were drawn from European studies in which only 10–52% of the participants recognized HPV as a risk factor for HNC. HPV-related HNC awareness in health care providers and medical/dental students showed a high variability among studies, being otolaryngology and dental sciences specialists the most conscious in comparison to general practitioners, who demonstrated a low level of awareness. Conclusions: There is a dangerous lack of awareness about HPV infection and its potential role in HNC among both general populations and health care practitioners. A great effort should be made to increase awareness in both practitioners and the general population on this topic, also aiming to increase the HPV vaccination coverage. Full article

This review article aims to summarize broadly recent developments in the treatment of HPV-associated cancers, including cervical cancer and head and neck squamous cell carcinoma. Relatively new treatments targeting the key HPV E6 and E7 oncoproteins, including gene editing with TALENs and CRISPR/Cas9, are discussed. Given the increased immunogenicity of HPV-related diseases, other therapies such as PRR agonists, adoptive cell transfer, and tumor vaccines are reaching the clinical trial phase. Due to the mechanism, immunogenicity, and reversibility of HPV carcinogenesis, HPV-related cancers present unique targets for current and future therapies. Full article

Growing scientific evidence suggests a link between the expression of toll-like receptor 4 (TLR4) and cervical cancer carcinogenesis. Specifically, a close relation between TLR4 expression and FIGO stage, lymph node metastases, and tumor size has been reported in cervical cancer. In the present study, we aimed to evaluate the relationship between TLR4 expression levels and human papillomavirus (HPV) infection and/or high-risk (hr) HPV integration status in patients with a histological diagnosis of high-grade squamous intraepithelial lesion (H-SIL), and squamous cell carcinoma (SCC) of the uterine cervix. Sixty biopsies of cervical neoplasia, comprising H-SIL (n = 20) and SCC (n = 40), were evaluated for TLR4 expression by immunohistochemistry. All samples were positive for high-risk HPV as confirmed by in situ hybridization (ISH) and broad-spectrum PCR followed by Sanger sequencing analysis. The intensity of TLR4 staining was higher in tissues negative for intraepithelial lesion or malignancy (NILM) than in H-SIL, and further reduced in SCC. Moreover, statistically significant differences have been observed in the percentage of TLR4 expression between NILM and H-SIL and between H-SIL and SCC, with higher percentages of expression in H-SIL than in SCC. Our results showed a significant downregulation of TLR4 in HPV-related H-SIL and SCC, compared to NILM. These data support the hypothesis that TLR4 expression is suppressed in HPV-driven oncogenesis. Full article