Search Results (6,032)

Non-human primates (NHPs) are considered important models for the study of reproductive diseases, due to their anatomical and physiological similarities to humans. However, studies on spontaneous lesions of the reproductive system in NHPs housed in zoos remain limited compared to those in laboratory animals. In this study, we report a retrospective analysis of female reproductive pathologies in 103 necropsied non-human primates from Italian zoos between 2007 and 2024. Only adult, intact, non-pregnant females with macroscopically visible reproductive lesions were included. Histopathological examination revealed reproductive tract lesions in 15 individuals (14.6%), including both non-neoplastic (cystic endometrial hyperplasia, adenomyosis, endometriosis) and neoplastic (leiomyomas, cervical and ovarian adenocarcinomas, and metastatic tumors) conditions. Leiomyoma was the most common tumor, particularly in the genus Macaca, while rare malignant neoplasms and metastatic lesions were identified in the great apes and in the New World species. The results suggest an age-related degenerative component and highlight interspecific differences in the distribution of lesions, probably related to the reproductive physiology of the various species. These results underline the importance of systematic post-mortem surveillance to improve the management of reproductive health of these captive populations and provide comparative insights with humans. Full article

Antigenicity and immunogenicity define a potent immunogen in vaccinology. Nowadays, there are simplified platforms to produce nanocarriers for small-peptide antigen delivery, derived from various infectious agents for the treatment of a variety of diseases, based on virus-like particles (VLPs). They have good cell-penetrating properties and protective action for target molecules from degradation. Human papillomavirus (HPV) causes anogenital warts and six types of cancer in infected women, men, or children, posing a challenge to global public health. The HPV capsid is composed of viral type-specific L1 and evolutionarily conserved L2 proteins. Produced in heterologous systems, the L1 protein can self-assemble into VLPs, nanoparticles sized around 50–60 nm, used as prophylactic vaccines. Devoid of the viral genome, they are safe for users, offering no risk of infection because VLPs do not replicate. The immune response induced by HPV VLPs is promoted by conformational viral epitopes, generating effective T- and B-cell responses. Produced in different cell systems, HPV16 L1 VLPs can be obtained on a large scale for use in mass immunization programs, which are well established nowadays. The expression of heterologous proteins was evaluated at various transfection times by transfecting cells with vectors encoding codon-optimized HPV16L1 and HPV16L2 genes. Immunological response induced by chimeric HPV16 L1/L2 VLP was evaluated through preclinical assays by antibody production, suggesting the potential of broad-spectrum protection against HPV as a prophylactic nanovaccine. These platforms can also offer promising therapeutic strategies, covering the various possibilities for complementary studies to develop potential preventive and therapeutic vaccines with broad-spectrum protection, using in silico new epitope selection and innovative nanotechnologies to obtain more effective immunobiologicals in combating HPV-associated cancers, influenza, hepatitis B and C, tuberculosis, human immunodeficiency virus (HIV), and many other illnesses. Full article

Cervical cancer (CC), which continues to be a major public health concern that causes cancer deaths among women worldwide, is mostly caused by persistent human papillomavirus (HPV) infection. This study suggests a dual-delay model of HPV-C infection dynamics that takes into account both cancerous delay and the immune response delay. We identify disease-free and diseased equilibria, investigate their local asymptotic stability, and show that the system is non-negative and bounded. We prove the global asymptotic stability of the equilibria by building Lyapunov functions and using the basic reproduction number $R_0$, and look into the existence of Hopf bifurcations. Additionally, we use forward sensitivity analysis to determine important control parameters. Lastly, the theoretical results were confirmed by numerical simulations. The study demonstrates that time delays play a crucial role in viral transmission and carcinogenesis. The process from HPV infection to the formation of cervical cancer is more correctly simulated by this model, which offers a theoretical mathematical basis for researching the pathophysiology of cervical cancer and developing clinical prevention and control measures. Full article

Background: Human papillomavirus (HPV) is responsible for a substantial fraction of anogenital and head and neck cancers (HNC). HPV-related cancers cause a heavy burden globally, with disparities across different cancers. We aimed to present an up-to-date global view of the patterns and incidence trends among HPV-related cancers. Methods: We collected data on HPV-related cancers from the GLOBOCAN 2022 database and the Cancer Incidence in Five Continents plus Compendium. Age-standardized incidence and mortality rate (ASIR and ASMR) were calculated to estimate the cancer burden. Spearman’s correlation tests were used to evaluate the associations with the Human Development Index (HDI). Joinpoint regression was conducted to evaluate the incidence trends in ASIR. Results: In 2022, 1,505,394 HPV-related cancer cases and 755,303 deaths were newly estimated worldwide, corresponding to an overall ASIR and ASMR of 20.9 and 10.2 per 100,000 people, respectively. Africa had the highest ASIR and ASMR compared with Asia, accounting for the most new cases and deaths. The primary cause was cervical cancer (ASIR 14.1 per 100,000 people); however, HNC exhibited the largest number of cases (685,204 cases). The total rates of HPV-related cancers were 1.3 times higher for ASIR and nearly three times higher for ASMR in low-HDI countries than in very high-HDI countries. A decreasing trend was observed for the ASIR of cervical cancer in most studied countries, compared to the increasing trends in HNC in females and anal cancer in both sexes. Conclusions: The global burden and trends of HPV-related cancers vary significantly among different cancer types according to region and sex. Particularly, cervical, HNC, and anal cancers should attract global attention. However, specific cancer types contributing to the heaviest burden should be identified at the country level to adjust resource allocation and improve access to quality health services. Full article

Objectives: Papillary thyroid carcinoma (PTC) frequently presents with cervical lymph node metastasis, even in small tumors, and lateral lymph node involvement serves as an important prognostic factor. Therapeutic lateral neck dissection is typically recommended when nodal metastasis is clinically evident, usually including levels II–V. However, the necessity of routine level II dissection in patients without clinical or radiologic evidence of level II involvement remains controversial, given its association with increased surgical morbidity, particularly injury to the spinal accessory nerve. Identifying reliable clinicopathological predictors of occult level II metastasis may enable more selective surgical approaches that minimize unnecessary dissection while preserving oncologic safety. Therefore, this study aimed to identify clinicopathological risk factors associated with occult level II lymph node metastasis in patients with PTC who have clinically positive lateral nodes but no clinical evidence of level II involvement. Methods: We retrospectively analyzed 1247 patients who underwent thyroidectomy for PTC between 2015 and 2022. Of these, 67 patients with clinically positive lateral lymph node metastasis and clinically negative Level II nodes who underwent therapeutic lateral neck dissection were included. Clinicopathological features were compared between patients with and without occult Level II metastasis. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors. Results: Among the 67 patients analyzed, 24 (35.8%) had occult Level II metastasis. Compared to those without, patients with occult Level II metastasis had significantly larger primary tumors (2.18 ± 1.31 cm vs. 1.51 ± 1.02 cm, p = 0.024), a greater number of central lymph node metastases (5.88 ± 4.41 vs. 3.37 ± 2.66, p = 0.005), larger maximum size of metastatic central lymph node (1.44 ± 1.07 cm vs. 0.87 ± 0.48 cm, p = 0.004), and a higher number of metastatic lateral lymph nodes (7.63 ± 3.75 vs. 3.19 ± 2.21, p < 0.001). Multivariate analysis identified the number of metastatic lateral lymph node as the only independent predictor of occult Level II involvement (OR = 1.57, 95% CI: 1.213–2.044, p = 0.001). The final multivariate model demonstrated a Nagelkerke R² of 0.46. ROC curve analysis confirmed good predictive performance (AUC = 0.85), and the optimal cut-off value was ≥ 5 metastatic lateral lymph nodes. Conclusions: A substantial proportion of patients with clinically negative Level II nodes harbor occult metastasis. The number of metastatic lateral lymph nodes is an independent predictor of occult Level II involvement and may assist in tailoring the extent of lateral neck dissection in patients with PTC. Full article

Chronic viral infections and virus-induced cancers have been actively studied for decades, with many significant advancements in basic science, disease cure, treatment, and prevention. Yet, today, these infections and pathologies remain major contributors to morbidity and mortality worldwide. The international online conference “VIRCAN2024: Chronic viral infections and cancer, openings for Vaccines and Cure” aimed to address the remaining issues, present the research carried out in this broad field, and prognose directions for its development. The conference covered oncogenicity mechanisms and new approaches in the development of treatments and vaccines. VIRCAN2024 was held on the platform of Riga Stradins University, Riga, Latvia. The conference was supported by the Latvian Science Council grant “Human papillomavirus genome associated correlates of disease progression and treatment response for cervical neoplasms and cancer”, and the scientific journal Vaccines (MDPI). This report summarizes the lectures and presentations given at the conference. Full article

Two series of tricyclic thieno[3,2-d]pyrimidines were synthesized, achieving yields of up to 97%. The tricyclic thieno[3,2-d]pyrimidines examined in this study are synthetic analogs of the deoxyvasicinone alkaloids, where the thiophene ring substitutes for the benzene ring. A systematic investigation was conducted on the scaffold-hopping strategy of these alkaloids, emphasizing the selective synthesis and anticancer properties of thieno[3,2-d]pyrimidines. The anticancer evaluation was performed on human cancer cell lines, specifically cervical HeLa and colon HT-29 carcinoma cells. Additional bioassays included cell migration analyses, cell cycle progression, apoptosis, and molecular docking analyses. Furthermore, molecular docking studies showed that the most active small molecule 6e is likely to disrupt the cell cycle process through targeting CDKs (Cyclin-dependent kinases), leading to the inhibition of tumor cell proliferation. Full article

Background/Objectives: The purpose of this review was to determine the impact of osteoporosis on outcomes after surgery for cervical deformity. Cervical deformity involves abnormal curvature or misalignment of the cervical spine, often resulting in a significant loss of quality of life and requiring surgical correction. While osteoporosis has been associated with hardware failure including screw loosening and cage migration in spine surgery, its role in cervical deformity remains unclear. Existing studies report mixed findings with regard to postoperative sequelae in patients with osteoporosis undergoing surgical correction of cervical deformity. Methods: A systematic review using PRISMA guidelines and MeSH terms involving spine surgery for cervical deformity and osteoporosis was performed. The Medline (PubMed) database was searched from 1990 to August 2022 using the following terms: “osteoporosis” AND “cervical” AND (“outcomes” OR “revision” OR “reoperation” OR “complication”). This review focused on radiographic outcomes, as well as post-operative complications. Results: Eight studies were included in the final analysis. Three papers assessed risk factors for the development of post-operative distal junctional kyphosis (DJK), but only one found osteoporosis as a predictor for DJK. Although three studies found that osteoporosis was not significantly associated with the incidence of surgical complications, one highlights osteoporosis as a predictor of complications at 90 days postoperatively (p < 0.001) and another associates osteoporosis with overall poor outcomes (p = 0.021). Furthermore, one study assessing the relationship between osteoporosis and reoperation found no association. Conclusions: Overall, our systematic review suggests that in patients undergoing surgery for cervical deformity, osteoporosis is not predictive of the need for reoperation or the development of postoperative complications, such as DJK, dysphagia, superficial infection, and others. These findings highlight the need for further study regarding the role of osteoporosis in surgical correction of cervical deformity. Full article

The goal of this study was to identify factors associated with pain sensitivity, procedural discomfort, and referral for surgical hysteroscopy, aiming to improve office hysteroscopy success rates. This was an observational prospective cross-sectional study that analyzed data from women who underwent outpatient hysteroscopy between October 2022 and October 2023. Epidemiological, clinical, and procedural data were collected from medical records. Pain levels were assessed using a visual analog scale (VAS), categorized as acceptable (0–6) or severe (7–10). Statistical analyses were performed to explore associations between patient characteristics and pain levels, with p-values < 0.05 considered significant. This study evaluated 1662 women. The mean age was 54.0 (±12.4) years, and 59.1% were postmenopausal. Nulliparity, menopause, lower body mass index (BMI), and fewer vaginal deliveries were associated with higher pain levels (p < 0.05). Cervical stenosis significantly increased procedural pain: 20.8% and 27.6% of patients with stenosis resolved during the procedure, respectively, reported severe pain. In the multivariate logistic regression analysis, protective factors against severe pain included having ≥2 vaginal deliveries (OR 0.53, 95% CI 0.39–0.72), patent internal (OR 0.53, 95% CI 0.38–0.75) and external cervical orifices (OR 0.47, 95% CI 0.30–0.72), presence of myomas (OR 0.53, 95% CI 0.34–0.83), and biopsy performance (OR 0.55, 95% CI 0.41–0.74). Severe pain, uterine lesions, and stenosis were the main reasons for surgical referral. Lower BMI, nulliparity, menopause, and cervical stenosis were significant predictors of increased pain during outpatient hysteroscopy. These findings may help identify patients at higher risk for procedural discomfort and support strategies to improve success of office hysteroscopy. Full article

Background/Objectives: Cervical cancer (CC), a highly prevalent female neoplasia, has been prevented through repeated cervicovaginal cytology, the so-called Pap test, across women’s lifespans. The now undebatable role of Human Papillomaviruses in the etiology of CC and the development of high-throughput automated molecular amplification diagnostic platforms is allowing for the replacement of the Pap test with HPV testing. The objective of this review is to contextualize the current strategies for cervical cancer screening using molecular assays. Methods: The many existing screening tools relying on molecular markers and their advantages and drawbacks are discussed. Results: Testing for oncogenic Human Papillomavirus DNA is presently the mainstay strategy for molecular screening, replacing cervicovaginal cytology. Conclusions: The presence of HPV-DNA is the most sensitive marker for cervical cancer and its precursor lesions. However, its adoption has led to an increase in the number of screening-positive subjects, generating extra demand for triage resources. New algorithms and technologies are fast being developed to address this need, moving toward risk-based management. Full article

DICER1 syndrome is a hereditary cancer predisposition syndrome, characterized by a large range of benign and malignant neoplasms. Patients with DICER1 syndrome have a broad phenotype, with pleuropulmonary blastoma, Sertoli–Leydig cell tumor, cystic nephroma, cervical embryonal rhabdomyosarcoma, cystic lung lesions, and thyroid follicular nodular disease being the most prevalent manifestations. The syndrome is caused by loss-of-function germline variants in the DICER1 gene, and DICER1-related tumors are characterized by second somatic hotspot variants in the RNase IIIb domain of DICER1. DICER1 encodes an endoribonuclease, which is important for RNA interference. This review describes the molecular mechanism of DICER1 function and the pathogenetic mechanisms of tumorigenesis. The purpose of this review is to describe the pathogenesis, genotype–phenotype correlation and tissue specificity of DICER1 syndrome. We conclude that there is a lack of knowledge about the exact molecular mechanisms of DICER1 function and more research is needed to determine the exact role of this altered protein in relation to pathogenesis. Full article

Background: Since liquid-based cytology (LBC) has replaced the conventional Papanicolaou test in cervical cancer screening programs, pre-analytical procedures—particularly the choice of LBC collection media—have become crucial to ensure the accuracy of high-risk (HR) HPV DNA testing. This study aims to evaluate whether the newly developed CytoPath^® LBC medium can serve as a reliable alternative to standard solutions. Methods: This study exploited cell lines to evaluate the stability, integrity, and recovery rate of genomic DNA at different fixation time points (1, 7, 14 and 40 days) and serial dilutions (1:5, 1:10 and 1:20) extracted from cell lines. These samples have also undergone quantitative Real-Time PCR (qPCR) based HR-HPV test to assess the relative performance of the new preservative solution in detecting viral DNA with respect to the standard reference. Results: Cervical cell lines preserved in both media demonstrated consistent DNA stability over time. DNA yields were comparable between the two media. Notably, the DNA Integrity Number (DIN) was higher in samples fixed with the CytoPath^® solution. HR-HPV detection by qPCR showed equivalent performance, regardless of the fixative used. Conclusions: The CytoPath^® fixative solution represents a valid alternative to standard preservation media, offering improved DNA integrity while maintaining equivalent performance in HR-HPV qPCR testing. Full article

Photodynamic therapy (PDT) is a promising, minimally invasive treatment for cervical cancer, but its efficacy is significantly limited by hypoxia—oxygen deficiency in the tumour microenvironment. The aim of this study was to present strategies to counteract hypoxia in PDT using the latest nanotechnologies. Based on a review of the literature available in PubMed/MEDLINE, Scopus, and Web of Science databases, covering the period from January 2024 to March 2025, nine original in vivo studies were identified that investigated the use of nanoparticle-based strategies to overcome hypoxia and enhance the efficacy of PDT in cervical cancer. A variety of approaches to improve tumour oxygenation are described, including the catalytic decomposition of hydrogen peroxide (H₂O₂) with manganese oxide (MnO₂), the use of bimetallic nanozymes (e.g., Au₂Pt), and FeOOH structures and oxygen storage and control systems (e.g., endoperoxides). Strategies to reduce oxygen consumption by cancer cells, such as nitric oxide (NO) release or inhibition of mitochondrial oxidative phosphorylation, are also discussed. The review shows that appropriately designed nanoparticles can effectively counteract hypoxia, enhancing the efficacy of PDT by intensifying reactive oxygen species (ROS) generation and modulating HIF-1α factor expression. The strategies presented here have the potential to significantly improve the efficacy of photodynamic therapy in the treatment of cervical cancer, especially under conditions of limited oxygen availability. Full article

This paper aims to assess the antiseptic capacity of a double-distilled ozonated water solution and compare it to standard presurgical antiseptic protocols based on chlorhexidine and alcohol. Sixty-three canine patients undergoing different surgical procedures (such as thoracic, abdominal, proximal limb, or cervical) were enrolled in the study. Following extensive preoperative clipping of the selected anatomical regions, four standardized skin areas (6 × 6 cm each) were aseptically sampled according to a predefined protocol: Area 1 received soap-based chlorhexidine followed by alcoholic chlorhexidine; Area 2 was prepared using a combination of soap-based chlorhexidine and ozonated water; Areas 3 and 4 underwent presurgical skin antisepsis with a combination of ethyl alcohol and ozonated water, and ozonated water alone, respectively. Two different samples per area were collected using bacteriological buffers in order to evaluate the bacterial count at 90 s and 180 s, respectively. Those samples were sown via streak plating on Petri dishes using PCA (plate count agar) as the medium. The determination of the total mesophilic bacterial count on Petri dishes was used to assess the efficacy of the antiseptics in different areas. Results show that ozonated bidistilled water demonstrated comparable or superior efficacy compared to other antiseptics tested in this study. Its integration into surgical protocols could enhance patient safety while controlling environmental concerns associated with the massive use of chemical antiseptics. Full article

Aberrant internal carotid arteries (ICA) are congenital vascular anomalies that occur from involution of the cervical portion of the ICA, which leads to enlargement of the normally small collateral inferior tympanic and caroticotympanic arteries. The inferior tympanic artery is a branch of the external carotid artery, usually the ascending pharyngeal artery, which extends through the inferior tympanic canaliculus (ITC), a small foramen located along the cochlea promontory. Aberrant ICAs can also be associated with a persistent stapedial artery (PSA), which is an abnormal vessel that arises from the petrous ICA and passes through the obturator foramen of the stapes. An aberrant ICA is a very important anomaly to recognize on imaging. Accurately describing its presence is important to help prevent iatrogenic injury during intervention. It is also important to distinguish an aberrant ICA from a lateralized ICA. The improvement of spatial resolution with photon counting detector (PCD)-CT has been proven to provide higher performance in detection of sub-centimeter vascular lesions compared to conventional energy-integrated detector (EID)-CT. PCD-CT also provides superior visualization of small skull-based foramina such as the inferior tympanic canaliculus, which can aid in more accurately characterizing an aberrant ICA (variant course without ITC involvement). Full article