Search Results (394)

Cervical cancer represents a significant global health challenge. Photodynamic therapy (PDT) appears to be a promising, minimally invasive alternative to standard treatments. However, the clinical efficacy of PDT is sometimes limited by the low solubility and aggregation of photosensitizers, their non-selective distribution in the body, hypoxia in the tumor microenvironment, and limited light penetration. Recent advances in nanoparticle and nanocomposite platforms have addressed these challenges by integrating multiple functional components into a single delivery system. By encapsulating or conjugating photosensitizers in biodegradable matrices, such as mesoporous silica, organometallic structures and core–shell construct nanocarriers increase stability in water and extend circulation time, enabling both passive and active targeting through ligand decoration. Up-conversion and dual-wavelength responsive cores facilitate deep light conversion in tissues, while simultaneous delivery of hypoxia-modulating agents alleviates oxygen deprivation to sustain reactive oxygen species generation. Controllable “motor-cargo” constructs and surface modifications improve intratumoral diffusion, while aggregation-induced emission dyes and plasmonic elements support real-time imaging and quantitative monitoring of therapeutic response. Together, these multifunctional nanosystems have demonstrated potent cytotoxicity in vitro and significant tumor suppression in vivo in mouse models of cervical cancer. Combining targeted delivery, controlled release, hypoxia mitigation, and image guidance, engineered nanoparticles provide a versatile and powerful platform to overcome the current limitations of PDT and pave the way toward more effective, patient-specific treatments for cervical malignancies. Our review of the literature summarizes studies on nanoparticles and nanocomposites used in PDT monotherapy for cervical cancer, published between 2023 and July 2025. Full article

Cervical cancer affects 661,000 women worldwide; as a result, new treatment alternatives are still being sought, with steroid oximes being the most prominent. However, the molecular targets where steroid oximes exert their anticancer activity remain unknown. In this study, reports of the activity in cell lines were obtained, and the targets associated with cervical cancer were identified using bioinformatics tools, based on two- and three-dimensional structural similarity analysis. Subsequently, molecular targets were analyzed via molecular docking using Schrödinger software v.2022-4 to determine their effects compared with reference drugs. Interrelated proteins and isolated proteins were observed, suggesting both the multi-target and single-target activity of steroid oximes. The analysis revealed that 60% of the 42 identified proteins had previously been reported in the literature and were associated with cervical cancer in processes related to cell proliferation, invasion, migration, and apoptosis. Among them, SRC, IGF1R, and MDM2 showed feasibility for multi-target interaction, which is consistent with the lower IC₅₀ values reported for oximes in cervical cancer cell lines (HeLa and CaSki). This finding suggests that steroid oximes are multi-target molecules that can inhibit the proteins associated with cervical cancer, particularly through the IGF1R, MDM2, and SRC pathways related to cell proliferation and apoptosis, serving as a guideline for the future design of new steroidal oximes. Full article

Background: The prevalence of BARD1 mutations in breast and ovarian cancers varies across different ethnic groups. Evaluating the cancer risk and clinical significance of BARD1 mutations in the local Chinese patients with breast cancer, ovarian cancer, or both is clinically important for designing an appropriate surveillance scheme. Methods: This study used a 30 gene panel to identify BARD1 germline mutations in 2658 breast and ovarian cancer patients. Results: Among this cohort, the BARD1 mutation prevalence was 0.45% for breast cancer and 0.29% for ovarian cancer. In our 12 mutation carriers, we identified eight types of mutation variants, including three novel mutations. BARD1 mutation carriers were more likely to have a family history of liver, prostate, and cervical cancers (p-values = 0.004, 0.018, and 0.037, respectively) than patients who tested negative for mutations. Among the BARD1 mutants, the majority of the breast tumors were invasive ductal carcinoma (NOS type) (10/11, 90.9%) of high-grade disease (9/9, 100%) and half of them were triple-negative breast cancer (5/10, 50%). Conclusions: Although the prevalence of BARD1 mutations is low and the penetrance is incomplete, we recommend including BARD1 in the test panel for breast cancer patients. Our data suggest that more comprehensive surveillance management may be considered in mutation carriers due to the familial aggregation of a relatively wide spectrum of cancers. Full article

Background/Objectives: CD318 (also known as CDCP1) is a transmembrane protein that is overexpressed in many cancers and contributes to tumor progression, invasion, and metastasis by activating SRC family kinases through phosphorylation. Emerging evidence also suggests that CD318 plays a role in modulating the tumor immune microenvironment, although its precise mechanism in tumor progression is still not well understood. Methods: To investigate this, we analyzed the expression and immune-related functions of CD318 using the publicly available data from The Cancer Genome Atlas (TCGA) across colorectal adenocarcinoma (COAD), cervical squamous cell carcinoma (CESC), lung adenocarcinoma (LUAD), and pancreatic adenocarcinoma (PAAD). Results: All four cancers exhibited a high level of CD318 expression. Notably, in CESC, LUAD, and PAAD, plasmin-mediated cleavage of CD318 leads to phosphorylation of SRC and protein kinase C delta (PKCδ), which activates HIF1α and/or p38 MAPK. These downstream effectors translocate to the nucleus and promote the transcriptional upregulation of TGFβ1, fostering an immunosuppressive tumor microenvironment through Treg cell recruitment. In contrast, this signaling cascade appears to be absent in COAD. Instead, our analysis indicate that intact CD318 in COAD interacts with the surface receptors CD96 and CD160, which are found on CD8⁺ T cells and NK cells. Conclusions: This interaction enhances cytotoxic immune responses in COAD by promoting CD8⁺ T cell and NK cell activity, offering a possible explanation for the favorable prognosis associated with high CD318 expression in COAD, compared to the poorer outcomes observed in CESC, LUAD, and PAAD. Full article

The recommended treatment for early-stage cervical cancer (FIGO 2018 stages IA–IB2 and selected IIA1) is surgery, followed by either observation or adjuvant therapy, based on individual risk factors. Surgical management has evolved from extensive radical procedures to more conservative strategies, allowing for fertility-preserving options in appropriately selected patients. In 2018, a landmark study (LACC trial) evaluated the surgical approach to radical hysterectomy, comparing open vs. minimally invasive surgery. The results demonstrated that minimally invasive surgery was associated with worse disease-free and overall survival, leading to guidelines changes that recommend the open radical hysterectomy as the new standard of care. More recently, results from the prospective randomized SHAPE trial demonstrated that in well-selected patients with low-risk early-stage cervical cancer, recurrence rates are comparable between simple hysterectomy and radical hysterectomy. An ongoing study, the CONTESSA trial, is evaluating the role of neoadjuvant chemotherapy in the setting of fertility preservation for lesions measuring 2–4 cm. In addition, ongoing studies are evaluating different surgical approaches for both simple hysterectomy (LASH trial) and radical hysterectomy (ROCC/GOG-3043 and RACC trials), with a focus on comparing oncologic outcomes. Attention has also turned to refining lymph node assessment. Sentinel lymph node biopsy has become a standard staging strategy with reduced morbidity. The SENTICOL I-II and SENTIX/ENGOT-Cx2 trials support its safety and diagnostic accuracy in early-stage disease. This article offers a comprehensive overview of recently published prospective trials that have shaped clinical practice in the management of early-stage cervical cancer. It focuses on surgical approaches and radicality, the role of sentinel lymph node mapping, and fertility-sparing treatments. The review further draws attention to ongoing investigations and novel studies that may influence future directions in the field. Full article

Objectives: This study aims to investigate the impact of Gossypol on human cervical cancer cells and elucidate its mechanism of action to establish a foundation for further clinical investigations. Methods: Cell proliferation, migration, and invasion were evaluated through CCK−8, wound healing, and Transwell assays. Fe₃O₄-BP-Gossypol (Fe₃O₄@Gossypol) conjugates were synthesized by linking Fe₃O₄ with Gossypol using benzophenone crosslinking. Successful conjugation was confirmed through scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and ultraviolet–visible spectrophotometry (UV-Vis). Subsequent to co-incubation with HeLa cell lysates, Fe₃O₄@Gossypol complexes facilitated the magnetic enrichment and purification of target proteins, which were identified using high-resolution mass spectrometry (HR-MS). The identified targets underwent KEGG pathway and GO analyses, followed by molecular docking with Gossypol. HeLa cells were exposed to Gossypol at concentrations of 7.48, 14.96, and 29.92 μmol·L⁻¹ for 48 h, and protein expression levels were quantified via Western blotting. Results: Gossypol notably suppressed cervical cancer cell proliferation, migration, and invasion. The integration of target fishing, network pharmacology, and molecular docking highlighted PIK3R2, MAPK1, and GRB2 as potential therapeutic targets. Western blot analysis revealed a dose-dependent reduction in PIK3R2, GRB2, and MAPK1 expression in Gossypol-treated groups compared to controls (p < 0.05). Conclusions: Gossypol may exhibit anti-cervical cancer effects by modulating the PI3K/AKT signaling pathway. Full article

Background: A number of factors might affect survival in oral squamous cell carcinoma. Nodal status is one of the most important prognosticators affecting survival. Studies have shown that pattern of invasion is an important aspect related to survival. Study design: retrospective single-center study (original article). Objectives: Our study aimed at evaluating the factors affecting mandibular invasion, lymph node metastasis, and extracapsular spread in oral squamous cell carcinoma and the survival factors associated with it. Methods: Patient records were evaluated to identify factors influencing primary outcome and survival. Cox regression analysis and Kaplan Meir were applied to evaluate the outcomes. Youden’s index was used to determine a cut-off value for depth of invasion and lymph node size affecting outcome. A p value of <0.05 was considered statistically significant. Results: The study evaluated 162 patients with oral cancer. The cut-off value for DOI was 6.5 mm, significantly affecting mandibular invasion and cervical metastasis. The cut-off value for lymph node size was 2.95 cm, significantly affecting extracapsular spread and overall survival. An aggressive pattern of invasion significantly affects mandibular invasion, cervical metastasis, and survival. Conclusion: An aggressive pattern of invasion and depth of invasion are independent risk factors for cervical lymph node metastasis and mandibular invasion. The independent risk factor for extracapsular spread is lymph node size. Lymph node metastasis and nodal size, pattern of invasion, mandibular invasion, and extracapsular spread are independent risk factors affecting overall survival. Full article

Precision prevention strategies for cervical cancer that integrate genetic biomarkers provide opportunities for personalized risk assessment and optimized preventive measures. An HPV infection–Precancerous–Cancer risk assessment model incorporating genetic polymorphisms and DNA methylation was developed to better understand the regression and progression of cervical lesions by HPV infection status. Utilizing a virtual cohort of 300,000 Taiwanese women aged 30 years and older, our model simulated the natural history of cervical cancer, capturing transitions from a healthy state through precancerous lesions (LSILs and HSILs) to invasive carcinoma and incorporating the possibility of regression between states. Genetic and epigenetic markers significantly influenced disease transitions, demonstrating heterogeneous risks among women with distinct molecular biomarker profiles. Guided by these individual risk profiles, tailored preventive strategies including varying intervals for Pap smear screening, HPV DNA testing, and HPV vaccination showed improved efficiency and effectiveness in reducing cervical cancer incidence compared to uniform approaches. The proposed dynamic transition model of cervical neoplasms incorporating genetic biomarkers can facilitate the development of an individualized risk-based approach for guiding precision prevention towards the goal of cervical cancer elimination. Full article

Background/Objectives: Cervical Intraepithelial Neoplasia (CIN) is a significant risk factor for the development of invasive cancer, and the histological detection of High-Grade CIN (CIN2+) during screening generally indicates the need for surgical removal of the lesion; cervical conization is the current gold standard of treatment. The recurrence risk for disease is reported to be up to 30%, based on data in the literature. Follow-up protocols mainly rely on High-Risk Human Papillomavirus (hrHPV) detection at six months post-treatment; if negative, this is considered the test of cure. This approach assumes that all patients have an equal risk of disease recurrence, regardless of individual characteristics. The objective of this study was to evaluate the individual recurrence risk using a mathematical model, analyzing the weight of various parameters and their associations in terms of recurrence development. Methods: We retrospectively examined 428 patients treated for CIN2+ at San Raffaele Hospital in Milan between January 2010 and April 2019. Clinical and pathological data were recorded and correlated with disease recurrence; three different variables, known to behave as significant prognostic factors, were analyzed: hrHPV persistence, the surgical margin status, Neutrophil–Lymphocyte Ratio (NLR), along with their relative associations. Data were used to engineer a mathematical model for the identification of different risk classes, allowing for the risk stratification of cases. Results: Surgical margins status, hrHPV persistence, and a high NLR index were demonstrated to act as independent and significant risk factors for disease recurrence, and their different associations significantly correlated with different recurrence rates. The mathematical model identified eight classes of recurrence probability, with Odds Ratios (ORs) ranging from 7.48% to 69.4%. Conclusions: The developed mathematical model may allow risk stratification for recurrence in a hierarchical fashion, potentially supporting the tailored management of follow-up, and improving the current protocols. This study represents the first attempt to integrate these factors into a mathematical model for post-treatment risk stratification. Full article

Background: Human papillomavirus (HPV) is a key cause of cervical and oropharyngeal cancers. Despite available vaccines, uptake remains low in Romania due to limited awareness and hesitancy. This study assessed HPV knowledge, vaccination status, and the presence of high-risk strains (16 and 18) in the saliva of dental students from Victor Babeș University in Timișoara. Methods: A cross-sectional study was conducted between February and March 2024, enrolling 199 dental students. Participants completed a 15-item questionnaire addressing HPV-related knowledge, vaccination status, lifestyle factors, and health history. Saliva samples were collected and analyzed using real-time PCR for the detection of HPV types 16 and 18. Logistic regression analysis was employed to identify predictors of vaccination uptake. Results: Only 10.6% of participants had received the HPV vaccine, although 96.9% acknowledged its safety and efficacy. Awareness was higher among females (88.1%) than males (84.3%), and vaccination rates were significantly greater among students under 25 years old (p = 0.0312). A total of 16.6% reported the presence of papillomas or warts. HPV DNA was detected in 10% of saliva samples. Conclusions: Although awareness of HPV was high, vaccination rates remained low, revealing a gap between knowledge and preventive action. Saliva-based screening shows promise as a non-invasive diagnostic tool, and integrating targeted education and advocacy into dental curricula may enhance public health outcomes in Romania. Full article

Objective: This study aims to explore the benefit of adjuvant chemoradiotherapy compared with radiotherapy alone following a radical hysterectomy with pelvic lymphadenectomy. The study focuses on patients with clinically early-stage squamous cervical cancer who have a single high-risk factor postoperatively. Methods: This retrospective study included women diagnosed between 2001 and 2018, with: (1) clinical tumour (cT) stage 1A2–2A2, (2) cervical squamous carcinoma, (3) treated with radical hysterectomy and pelvic lymphadenectomy (4) followed by adjuvant (chemo)radiotherapy, and with (5) one high-risk factor (i.e., positive resection margins, parametrial involvement, or pelvic lymph node metastases). Recurrence-free and overall survival were estimated using Kaplan−Meier and Cox proportional hazards analyses. Inverse probability treatment weighting was used to adjust for confounding. Results: Of the 122 patients with squamous cell carcinoma and one high-risk factor, 76 (62%) received adjuvant chemoradiotherapy and 46 (38%) received adjuvant radiotherapy alone. Larger tumour size, tumour grade 3, and pathological parametrial invasion were more common in the radiotherapy group, while patients who received chemoradiotherapy were more likely to have multiple lymph node metastases. The unadjusted and for confounding adjusted 5-year survival rates were comparable between the adjuvant chemoradiotherapy and radiotherapy groups for both recurrence-free survival (85% versus 87%; p = 0.58, and 84% versus 91%; p = 0.49) and overall survival (84% versus 87%; p = 0.51, and 84% versus 91%; p = 0.49). Conclusions: Adding chemotherapy to radiotherapy may not improve survival of patients with early squamous cervical cancer treated with radical hysterectomy and pelvic lymphadenectomy, and with a single postoperative high-risk factor. Full article

Background: Cervical cancer continues to pose a significant global health challenge, particularly in low-resource regions with limited access to advanced diagnostics. Cervical conization can occasionally uncover invasive carcinoma in patients initially suspected of having only pre-invasive lesions. This study assessed the platelet-to-lymphocyte ratio (PLR) as a potential predictive biomarker for identifying invasive disease in patients undergoing a loop electrosurgical excision procedure (LEEP). Methods: A retrospective study was conducted on 371 patients who underwent LEEP conization for cervical dysplasia. Preoperative PLR values were collected and compared across final histopathological categories (negative, low-grade, high-grade, invasive carcinoma) using the Kruskal–Wallis test, followed by Mann–Whitney U tests for pairwise comparisons. Receiver operating characteristic (ROC) analysis was used to evaluate diagnostic accuracy. Results: PLR values above 7.7 were significantly associated with HPV positivity, increasing with histopathological severity. There were significant PLR differences across the outcome groups (p = 0.005), with notably higher values in cases of invasive carcinoma (p < 0.01). ROC analysis showed moderate diagnostic utility (AUC ≈ 0.72); at a PLR cutoff of ~11.9, sensitivity was 65% and specificity 81%. Conclusions: The PLR cutoff of 7.7 was associated with HPV positivity, while a higher cutoff of 11.93 was identified for predicting invasive cervical cancer. These findings support that preoperative PLR is a non-invasive, clinically relevant marker correlated with lesion severity, offering potential for preoperative risk stratification, particularly where advanced diagnostics are limited. Full article

Aims:This study aimed to identify the prognostic value of tumor invasion distance (TID) based on MRI findings in cervical-cancer (CC) patients treated with radiotherapy (RT). Methods: A total of 218 CC patients diagnosed at Fujian Cancer Hospital from December 2018 to December 2019 were included in the study. Cox regression analyses were conducted to identify independent prognostic factors for overall survival (OS), including low 1/3 vaginal involvement, a longer TID, and RT without chemotherapy. These factors were subsequently used to construct a nomogram for individualized risk prediction. Kaplan–Meier survival analysis was employed to evaluate survival outcomes and establish a risk stratification system. The performance of the new stratification was assessed using the linear trend χ² test, Akaike information criterion, and Harrell’s concordance index. Results: A longer TID was associated with worse 3-year OS (p < 0.001, HR: 3.42, 95% CI: 1.67–7.00). A longer TID, lower 1/3 vaginal involvement, and concurrent chemotherapy were independent prognostic survival factors for CC patients. Compared with the 2018 FIGO staging system, the new risk stratification system provided better monotonicity with a higher linear trend χ² value (28.03 vs. 9.35), better discriminatory ability with smaller Akaike information criterion (312 vs. 331), and a greater Harrell C statistic (0.74 vs. 0.65) for predicting 3-year OS. Conclusions: This was the first study to demonstrate the prognostic value of TID in CC patients who received RT. The new risk stratification system based on TID could complement the 2018 FIGO staging system in identifying high-risk patients for more intense treatment and care. Further prospective research with larger samples is warranted to confirm the significance of TID for CC patients treated with RT. Full article

Standard of Care (SOC) for locally advanced cervical cancer is represented by external beam radiation therapy concurrent with platinum-based chemotherapy and immunotherapy (cCIRT) followed by brachytherapy boost and immunotherapy maintenance. In some instances, it is impossible to perform brachytherapy due to patient and/or cancer issues. In these circumstances, an external beam boost could be delivered. Using a robotic arm LINAC, it is mandatory to use intramucosal implanted fiducials which are needed for tumour tracking. To avoid invasive procedures, we developed an original intravaginal 3D-printed universal device containing gold fiducials embedded within it. In this paper, we describe the step-by-step procedure that allowed us to obtain the utility model patent, including the in vivo test (feasibility, reproducibility, device compliance) on seven patients within the study protocol “STereotActic Radiotherapy Boost in locally Advanced Cervical carcinoma patientS” (STARBACS). Full article

Background/Objectives: Papillary thyroid carcinoma (PTC) accounts for the majority of thyroid cancers, with lymph node metastasis, including skip metastasis (SM), playing a crucial role in guiding prognosis and therapeutic planning. SM, characterized by lateral lymph node spread in the absence of central compartment involvement, has been observed in PTC with a wide range of reported frequencies. The identification of risk factors for SM is crucial for preoperative evaluation and surgical planning. This research aims to explore the clinicopathological features and potential risk factors linked to SM in patients with PTC, while also offering valuable insights for preoperative risk evaluation. Methods: A retrospective cohort study was conducted on 81 PTC patients who underwent central and lateral cervical lymph node dissection (LND) in our center. Clinical, demographic, and pathological data, including age, sex, tumor size, location, subtype, extrathyroidal extension, lymphovascular invasion, and the number of lymph node metastases were analyzed. Clinicopathological characteristics were analyzed between SM-positive and SM-negative patient groups using suitable statistical methods. Additionally, a regression analysis was performed to identify the risk factors for SM. Results: Of the 81 patients, 17.3% (n = 14) were diagnosed with skip metastasis (SM). The SM-positive group had a significantly higher age (p = 0.006), smaller tumor size (p < 0.001), and higher rates of extrathyroidal extension (p = 0.006). The proportion of female patients was elevated in the SM-positive group, but this observation did not achieve statistical significance (p = 0.128). Tumors located in the upper pole were more common in the SM-positive group (p = 0.016). Multivariate analysis revealed that female sex, older age, and tumor location in the upper pole were significant risk factors for SM (p = 0.031, p = 0.004, and p = 0.017, respectively), while a lower number of lateral lymph node metastases was significantly associated with SM (p = 0.010). Additionally, an age over 43.5 years predicted SM with a sensitivity of 78.6% and a specificity of 72.7%. Conclusions: Skip metastasis is not uncommon in PTC and may be associated with older age, female sex, upper pole tumor location, and fewer lateral lymph node metastases. Recognizing these factors during preoperative assessment may aid in anticipating atypical lymphatic spread patterns and optimizing surgical strategies. Full article