Search Results (22)

Despite advancements in multidisciplinary treatment, esophagectomy remains the primary curative treatment for esophageal cancer. Given that lymph node metastases can spread from the cervical to abdominal regions, three-field lymph node dissection has been established as a standard approach. However, this highly invasive procedure involves multiple anatomical regions—thoracic, abdominal, and cervical—leading to significant surgical burden. To reduce surgical invasiveness, minimally invasive esophagectomy (MIE) has become increasingly common worldwide. With its adoption and advancements in multidisciplinary therapy, discussions have emerged regarding the potential omission of lymph node dissection in selected cases. Since the introduction of robot-assisted minimally invasive esophagectomy (RAMIE) in 2004, this technique has progressively replaced conventional MIE. Robotic systems—equipped with a magnified 3D camera, articulated instruments, and tremor filtering—allow surgeons to perform complex procedures with greater precision than manual techniques. One randomized controlled trial (RCT) has demonstrated fewer postoperative complications with RAMIE compared to open esophagectomy. Additionally, RAMIE has been shown to enable more extensive lymph node dissection around the left recurrent laryngeal nerve than conventional MIE. However, the long-term oncological benefits of RAMIE remain unproven, as no RCTs have definitely confirmed its impact on long-term survival in esophageal cancer patients. Ongoing randomized trials are expected to provide further insights into its prognostic benefits. Full article

Stereotactic body radiation therapy has emerged as a promising alternative to brachytherapy, delivering high doses to tumors with precision while sparing surrounding organs. This systematic review evaluates the role of SBRT as a boost for patients who are ineligible for brachytherapy. A total of 17 studies, involving 288 patients, were analyzed, focusing on dosimetric parameters and toxicity. The radiation regimens varied in dose and fractionation schedules, with external beam doses ranging from 44 to 61.6 Gy, and SBRT boost doses ranging from 5 to 30 Gy. The total EQD₂ doses were between 50.5 and 92.4 Gy. The results indicate adequate tumor control with SBRT, with local control rates ranging from 57% to 95.5%. The acute genitourinary and gastrointestinal toxicities were mostly grade 1 or 2, while late toxicities were less common. The overall survival rates varied between 34% and 96%. These results suggest that SBRT boost offers a viable option for cervical cancer patients ineligible for brachytherapy, with acceptable toxicity and promising survival outcomes. Nevertheless, the scarcity of data, which mainly originate from small studies with patients having varied stages of disease, as well as the lack of long-term follow up with SBRT, should encourage clinicians to utilize brachytherapy whenever suitable as a boost in these patient cohorts. Full article

NF-κB, a multifunctional transcription factor, is linked to cancer initiation and progression. As a key immune mediator, it may play a crucial role in HPV-induced cervical carcinogenesis. However, consensus is lacking on the activation timing of NF-κB during the transition from cervical intraepithelial neoplasia (CIN) to cervical squamous cell carcinoma (CSCC). In this study, immunohistochemical analysis was performed to examine RELA, one of the important members of the NF-κB family, and phospho-RELA expression in different cervical lesions. Then, we analyzed NF-κB regulation of differentially expressed genes (DEGs) in cervical lesions vs. normal tissues. Gene enrichment identified oncogenic DEGs, followed by expression and survival analyses. The impact of NF-κB activation on cervical cell proliferation, migration, and oncogenic regulation, as well as the effects of inhibiting NF-κB, were examined. Our study showed that NF-κB activation starts in cervical simple hyperplasia and intensifies as CIN evolves to CSCC. NF-κB-regulated DEGs show stage-specific functions: immune regulation in CIN and cancer promotion in CSCC. Short-term NF-κB activation boosts cervical cell proliferation and migration, which is reversible by an NF-κB inhibitor. Long-term NF-κB activation promotes the expression of cancer-promoting genes in normal cells and also maintains them in cancer tissues, which is linked to poorer prognosis. Inhibiting NF-κB downregulates these genes in cancer cells and suppresses the oncogenic abilities of cervical cancer cells. Collectively, NF-κB activation initiates during the simple hyperplasia stage of cervical cells, stimulating proliferation, migration, and oncogene expression. Throughout the transition from CIN to CSCC, NF-κB activation progressively intensifies, and its long-term activation promotes carcinogenesis. Thus, NF-κB is crucial in mediating cervical oncogenic transformation. Full article

Radioresistance remains a major obstacle in cervical cancer treatment, frequently engendering tumor relapse and metastasis. However, the details of its mechanism of action remain largely enigmatic. This study delineates the prospective impacts of short-form human T-cell lymphoma invasion and metastasis 2 (TIAM2S) involving the radiation resistance of cervical cancer. In this study, we established three pairs of radioresistant (RR) cervical cancer cells (HeLa, C33A and CaSki) and their parental wild-type (WT) cells. We revealed a consistent augmentation of TIAM2S, but not long-form human T-cell lymphoma invasion and metastasis 2 (TIAM2L) were displayed in RR cells that underwent a 6 Gy radiation administration. Remarkably, RR cells exhibited decreased radiosensitivity and abridged apoptosis, as estimated through a clonogenic survival curve assay and Annexin V/Propidium Iodide apoptosis assay, respectively. TIAM2S suppression increased radiosensitivity and enhanced cell apoptosis in RR cells, whereas its forced introduction modestly abolished radiosensitivity and diminished WT cell apoptosis. Furthermore, TIAM2S overexpression notably aggravated RR cell migration, whereas its blockage reduced WT cell mobilities, as confirmed by an in vitro time-lapse recording assay. Notably, augmented lung localization was revealed after a tail-vein injection of CaSki-RR cells using the in vivo short-term lung locomotion BALB/c nude mouse model. TIAM2S impediment notably reduced radioresistance-increased lung locomotion. This study provides evidence that TIAM2S may operate as an innovative signature in cervical cancer that is resistant to radiotherapy. It displays multi-faceted roles including radioprotection, restricting apoptosis, promoting cell proliferation, and escalating cell migration/metastasis. Targeting TIAM2S, together with conventional radiotherapy, may be an innovative strategy for intensifying radiosensitivity and protecting against subsequent uncontrolled tumor growth and metastasis in cervical cancer treatment. Full article

Therapeutic vaccination can harness the body’s cellular immune system to target and destroy cancerous cells. Several treatment options are available to eliminate pre-cancerous and cancerous lesions caused by human papillomaviruses (HPV), but may not result in a long-term cure. Therapeutic vaccination may offer an effective, durable, and minimally intrusive alternative. We developed mucosally delivered, recombinant, non-replicating human adenovirus type 5 (rAd5)-vectored vaccines that encode HPV16′s oncogenic proteins E6 and E7 alongside a molecular dsRNA adjuvant. The induction of antigen-specific T cells and the therapeutic efficacy of rAd5 were evaluated in a mouse model of HPV tumorigenesis where E6E7-transformed cells, TC-1, were implanted subcutaneously in C57BL/6 mice. After tumor growth, mice were treated intranasally with rAd5 vaccines expressing the wildtype form of E6E7 (rAd5-16/E6E7_Wt) in combination with an anti-PD-1 antibody or isotype control. Animals treated with rAd5-16/E6E7_Wt with and without anti-PD-1 had significant reductions in tumor volume and increased survival compared to controls. Further, animals treated with rAd5-16/E6E7_Wt had increased CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) and produced a cytotoxic tumor microenvironment. In a second study, the immunogenicity of a non-transformative form of E6E7 (rAd5-16/E6E7_Mu) and a vaccine encoding predicted T cell epitopes of E6E7 (rAd5-16/E6E7_epi) were evaluated. These vaccines elicited significant reductions in TC-1 tumor volume and increased survival of animals. Antigen-specific CD8+ T effector memory cells were observed in the animals treated with E6E7-encoding rAd5, but not in the rAd5-empty group. The work described here demonstrates that this mucosal vaccination can be used therapeutically to elicit specific cellular immunity and further identifies a clinical candidate with great potential for the treatment and prevention of human cervical cancer. Full article

As cancer remains a significant global health challenge, there is an increasing need for novel therapeutic approaches. We investigated the antitumor potential of Juniperus communis berry essential oil on cervical cancer HeLa and colorectal HCT 116 cells. Cytotoxicity was evaluated through the MTT assay, revealing concentration-dependent reductions in cell viability. A clonogenic assay demonstrated long-term cytotoxic effects. Apoptosis markers were assessed via flow cytometric analysis and showed an induction of the intrinsic pathway in both cell lines, demonstrated by the elevated levels of cleaved caspase-3, Bax/Bcl-2 ratio, JC-10 monomer formation, and cytochrome C migration to the cytosol. The treatment inhibited cell-survival pathways in HCT 116 cells and arrested HeLa cells in the S phase. An extensive molecular docking screening provided insight into the binding affinity and interaction patterns of the essential oil components with NADH ubiquinone oxidoreductase and superoxide dismutase enzymes, further confirming the induction of the intrinsic pathway of apoptosis. The obtained in silico and in vitro results indicated the anticancer potential of J. communis berry essential oil as it interferes with cancer cell molecular mechanisms. Our findings highlight J. communis berry essential oil as a promising natural agent with anticancer potential. Full article

This systematic review evaluates the clinical outcomes and molecular predictors of response to pembrolizumab in patients with advanced and metastatic cervical cancer. We adhered to the PRISMA guidelines for systematic reviews, conducting a database search in PubMed, Scopus, and Embase. The eligibility criteria centered on clinical outcomes, including the overall survival (OS), progression-free survival (PFS), and immune-related biomarkers post-pembrolizumab therapy. We included both prospective and retrospective studies that detailed clinical outcomes and molecular characteristics predictive of therapeutic response. Our search yielded six studies involving 846 patients treated with pembrolizumab from 2017 to 2022. The meta-analysis of these studies showed that pembrolizumab, used as monotherapy or in combination with chemotherapy, extended the OS by a weighted median of 10.35 months and the PFS by 8.50 months. The treatment demonstrated a pooled objective response rate (ORR) of 22.39%, although the I² test result of 67.49% showed a high heterogeneity among the studies. Notably, patients with high PD-L1 expression (CPS ≥ 10) experienced improved outcomes in terms of the PFS and OS. The most common complications were fatigue, diarrhea, and immune-related adverse events. Pembrolizumab significantly enhances clinical outcomes in metastatic cervical cancer, particularly among patients with high PD-L1 expression. The drug maintains a good safety profile, reinforcing its treatment potential for patients with advanced and metastatic cervical cancer. Future studies should explore long-term effects and strategies to integrate pembrolizumab optimally into current treatment regimens, aiming to maximize patient benefits and effectively manage side effects. Full article

Prostate cancer (PCa) remains a common cancer with high mortality in men due to its heterogeneity and the emergence of drug resistance. A critical factor contributing to its lethality is the presence of prostate cancer stem cells (PCSCs), which can self-renew, long-term propagate tumors, and mediate treatment resistance. MicroRNA-34a (miR-34a) has shown promise as an anti-PCSC therapeutic by targeting critical molecules involved in cancer stem cell (CSC) survival and functions. Despite extensive efforts, the development of miR-34a therapeutics still faces challenges, including non-specific delivery and delivery-associated toxicity. One emerging delivery approach is ligand-mediated conjugation, aiming to achieve specific delivery of miR-34a to cancer cells, thereby enhancing efficacy while minimizing toxicity. Folate-conjugated miR-34a (folate–miR-34a) has demonstrated promising anti-tumor efficacy in breast and lung cancers by targeting folate receptor α (FOLR1). Here, we first show that miR-34a, a TP53 transcriptional target, is reduced in PCa that harbors TP53 loss or mutations and that miR-34a mimic, when transfected into PCa cells, downregulated multiple miR-34a targets and inhibited cell growth. When exploring the therapeutic potential of folate–miR-34a, we found that folate–miR-34a exhibited impressive inhibitory effects on breast, ovarian, and cervical cancer cells but showed minimal effects on and targeted delivery to PCa cells due to a lack of appreciable expression of FOLR1 in PCa cells. Folate–miR-34a also did not display any apparent effect on PCa cells expressing prostate-specific membrane antigen (PMSA) despite the reported folate’s binding capability to PSMA. These results highlight challenges in the specific delivery of folate–miR-34a to PCa due to a lack of target (receptor) expression. Our study offers novel insights into the challenges and promises within the field and casts light on the development of ligand-conjugated miR-34a therapeutics for PCa. Full article

Purpose: No randomized study with a long-term follow-up has investigated the effect of pretreatment 18-fluorodeoxyglucose positron emission tomography–computed tomography (¹⁸FDG-PET–CT) on the survival of patients with stage IB-IIA cervical cancer receiving curative surgery. Therefore, in this propensity score–matched, population-based cohort study, we investigated the effect of preoperative ¹⁸FDG-PET–CT on the survival outcomes of patients with potentially resectable cervical cancer. Patients and Methods: We included 2550 patients with stage IB-IIA cervical cancer receiving curative surgery with complete data on clinical stages. The patients were categorized into two 1:4 propensity, score–matched groups depending on whether they underwent pretreatment ¹⁸FDG-PET–CT, and their outcomes were compared. Results: We included 2030 and 520 patients with cervical cancer in the non-pretreatment and pretreatment PET–CT groups, respectively. Multivariable analyses revealed that the most prominent correlation between preoperative PET–CT and all-cause death was observed in the patients with stage IB–IIA cervical cancer receiving surgery (aHR [95% CI]: 1.16 [0.83–1.63]; p = 0.3752). Conclusions: Preoperative ¹⁸FDG-PET–CT was not associated with longer survival in the patients with clinical stage IB–IIA cervical cancer receiving curative surgery. Full article

(1) Background: To report the long-term clinical outcomes of computer-tomography (CT)-guided brachytherapy (BT) for locally advanced cervical cancer. (2) Methods: A total of 135 patients with FIGO stage IB-IVA cervical cancer treated with definitive radiotherapy +/− chemotherapy with an IGABT boost at Queen Mary Hospital, Hong Kong, between November 2013 and December 2019 were included. Treatment included pelvic radiotherapy 40 Gy/20 Fr/4 weeks +/− chemotherapy then CT-guided BT (7 Gy × 4 Fr) and a sequential parametrial boost. The primary outcome was local control. Secondary outcomes were pelvic control, distant metastasis-free survival, overall survival (OS) and late toxicities. (3) Results: The median follow-up was 53.6 months (3.0–99.6 months). The five-year local control, pelvic control, distant metastasis-free survival and OS rates were 90.7%, 84.3%, 80.0% and 87.2%, respectively. The incidence of G3/4 long-term toxicities was 6.7%, including proctitis (2.2%), radiation cystitis (1.5%), bowel perforation (0.7%), ureteric stricture (0.7%) and vaginal stenosis and fistula (0.7%). Patients with adenocarcinomas had worse local control (HR 5.82, 95% CI 1.84–18.34, p = 0.003), pelvic control (HR 4.41, 95% CI 1.83–10.60, p = 0.001), distant metastasis-free survival (HR 2.83, 95% CI 1.17–6.84, p = 0.021) and OS (HR 4.38, 95% CI: 1.52–12.67, p = 0.003) rates. Distant metastasis-free survival was associated with HR-CTV volume ≥ 30 cm³ (HR 3.44, 95% CI 1.18–9.42, p = 0.025) and the presence of pelvic lymph node (HR 3.44, 95% CI 1.18–9.42, p = 0.025). OS was better in patients with concurrent chemotherapy (HR 4.33, 95% CI: 1.40–13.33, p = 0.011). (4) Conclusions: CT-guided BT for cervical cancer achieved excellent long-term local control and OS. Adenocarcinoma was associated with worse clinical outcomes. (4) Conclusion: CT-guided BT for cervical cancer achieved excellent long-term local control and OS. Adenocarcinoma was associated with worse clinical outcomes. Full article

Background: Considerable efforts have been carried out over the past 30 years to support patients with advanced cervical cancer. Throughout this time, Eastern European countries have been left aside from the decision-making groups on this matter, hence the absence of similar studies in this geographical area. In these countries, the quality of life (QoL) of patients with cervical cancer might be considered a “caprice”, and the discomforts they encounter following pelvic exenteration for cervical cancer are often perceived as a “normal phenomenon”. Methods: This study examined forty-seven patients submitted to pelvic exenteration followed up for nine years after the surgical intervention. The first objective of this study is to identify the prognostic factors that influence the overall survival (OS) of patients undergoing pelvic exenteration for FIGO stage IVA, recurrent or persistent cervical cancer after previous conclusive treatments. The second objective is to assess the QoL of the surviving patients using the QLQ-C30 and QLQ-CX24 standardized questionnaires. Results: The mean age of the participants was 54 years (range 36–67). At the time of the study, there were 25 living patients (53.2%), the 3-year OS was 61%, and the 5-year OS was 48.7%. Cox regression analysis recognized parameter invasion, pelvic lymph node metastases, positive resection margins, early postoperative complications, and infralevatorian pelvic exenteration as negative prognostic factors influencing the OS (p < 0.05). Of the 25 survivors, 18 patients answered the QoL questionnaires. The cost of favorable survival has been translated into poor overall QoL, unsatisfactory functional, social, and symptom scores, a high prevalence of cervical cancer-specific symptoms such as lymphedema, peripheral neuropathy, severe menopausal symptoms, distorted body image, and lack of sexual desire. The lower scores are comparable to the only three studies available in the literature that assessed the QoL of patients undergoing pelvic exenteration precisely for cervical cancer. Conclusions: Despite its retrospective nature and some limitations, this paper, similar to other studies, shows a decent OS but with a marked adverse impact on QoL, suggesting the importance of adequate psycho-emotional and financial support for these patients following pelvic exenteration. This study also contributes to the current knowledge regarding advanced cervical cancer treatment, depicting survival, prognostic factors, and QoL of patients undergoing pelvic exenteration for cervical cancer in a reference center in Eastern Europe. Our study can provide a comparison for future prospective randomized trials needed to confirm these results. Full article

(1) Background: Cervical cancer patients have been found to have worse quality of life (QoL) scores due to cancer treatment, not only when compared to the general population, but also when compared to other gynecological cancer survivors. In Eastern European developing countries, the health care system often cannot afford the uppermost standardized treatment for these patients. In the absence of a comparable study in our country, the authors’ aim for this retrospective cross-sectional observational study was to evaluate the overall survival (OS) and the QoL o cervical cancer survivors; (2) Methods: 430 patients were analyzed. The first objective is to evaluate the OS rates of patients with cervical cancer stages IA2 to IIB undergoing radical hysterectomy (RH) +/− neoadjuvant or adjuvant radiotherapy +/− chemoradiotherapy treatment combinations. The second objective is to assess their QoL, using two standardized questionnaires issued by the European Organisation for Research and Treatment of Cancer (EORTC), namely QLQ-C30 and QLQ-CX24. (3) Results: The mean age of the participants was 51 years (22–76) and the average follow-up time was 65 months (2–128). At the time of the analysis, 308 out of 430 patients were alive, with a mean five-year OS of 72.4%. The multivariate Cox regression analysis identified stage IIB, parametrial invasion, and the lymph node metastases as independent prognostic risk factors negatively impacting the OS. Of the 308 patients still alive at the time of the analysis, 208 (68%) answered the QoL questionnaires. The QLQ-C30 shows a good long-term Global QoL of 64.6 (median), good functioning scores, and a decent symptom scale value. However, the EORTC QLQ-CX24 showed high values of cervical cancer-specific symptoms, namely: lymphedema, peripheral neuropathy, severe menopausal symptoms, and distorted body-image perception. The results also indicate a significant decline in the quality of sexual life with a low sexual enjoyment and decreased level of sexual activities. (4) Conclusion: Despite a good OS, in this setting of patients, cervical cancer survivors have a modest QoL and sexual function. Our study may provide a comparison for future randomized, controlled trials in Eastern European countries needing to confirm these results. Full article

Purpose: Cervical cancer that is invisible on magnetic resonance imaging (MRI) may suggest lower tumor burden than physical examination. Recently, 3 tesla (3T) MRI has been widely used prior to surgery because of its higher resolution than 1.5T MRI. The aim was to retrospectively evaluate the utility of 3T MRI in women with early cervical cancer in determining the necessity of less invasive surgery. Materials and methods: Between January 2010 and December 2015, a total of 342 women with FIGO stage IB1 cervical cancer underwent 3T MRI prior to radical hysterectomy, vaginectomy, and lymph node dissection. These patients were classified into cancer-invisible (n = 105) and cancer-visible (n = 237) groups based on the 3T MRI findings. These groups were compared regarding pathologic parameters and long-term survival rates. Results: The cancer sizes of the cancer-invisible versus cancer-visible groups were 11.5 ± 12.2 mm versus 30.1 ± 16.2 mm, respectively (p < 0.001). The depths of stromal invasion in these groups were 20.5 ± 23.6% versus 63.5 ± 31.2%, respectively (p < 0.001). Parametrial invasion was 0% (0/105) in the cancer-invisible group and 21.5% (51/237) in the cancer-visible group (odds ratio = 58.3, p < 0.001). Lymph node metastasis and lymphovascular space invasion were 5.9% (6/105) versus 26.6% (63/237) (5.8, p < 0.001) and 11.7% (12/105) versus 40.1% (95/237) (5.1, p < 0.001), respectively. Recurrence-free and overall 5-year survival rates were 99.0% (104/105) versus 76.8% (182/237) (p < 0.001) and 98.1% (103/105) versus 87.8% (208/237) (p = 0.003), respectively. Conclusions: 3T MRI can play a great role in determining the necessity of parametrectomy in women with IB1 cervical cancer. Therefore, invisible cervical cancer on 3T MRI will be a good indicator for less invasive surgery. Full article

Cervical cancer is recognized as a serious public health problem since it remains one of the most common cancers with a high mortality rate among women despite existing preventative, screening, and treatment approaches. Since Human Papillomavirus (HPV) was recognized as the causative agent, the preventative HPV vaccines have made great progress over the last few years. However, people already infected with the virus require an effective treatment that would ensure long-term survival and a cure. Currently, clinical trials investigating HPV therapeutic vaccines show a promising vaccine-induced T-cell mediated immune response, resulting in cervical lesion regression and viral eradication. Among existing vaccine types (live vector, protein-based, nucleic acid-based, etc.), deoxyribonucleic acid (DNA) therapeutic vaccines are the focus of the study, since they are safe, cost-efficient, thermostable, easily produced in high purity and distributed. The aim of this study is to assess and compare existing DNA therapeutic vaccines in phase I and II trials, expressing HPV E6 and E7 oncoproteins for the prospective treatment of cervical cancer based on clinical efficacy, immunogenicity, viral clearance, and side effects. Five different DNA therapeutic vaccines (GX-188E, VGX-3100, pNGVL4a-CRT/E7(detox), pNGVL4a-Sig/E7(detox)/HSP70, MEDI0457) were well-tolerated and clinically effective. Clinical implementation of DNA therapeutic vaccines into treatment regimen as a sole approach or in combination with conservative treatment holds great potential for effective cancer treatment. Full article

Background: Squamous cell carcinoma is the most frequent malignant cancer of the oral cavity. Metastasis involvement is one of the most relevant prognostic factors in terms of survival probability. Patients with oral cancers often undergo extensive en bloc resective surgery of the mandible and maxilla, with or without cervical nodal dissection, based on the presence or occult risk of regional metastases. Several factors affect the choice of flap, to recover aesthetics and function. Case Presentation: The case of a 60-year-old man who underwent maxillectomy with neck dissection as well as a reconstruction with a combination of multiple vascularized free flaps is presented. Conclusions: The excellent integration of the free flaps and the total absence of complications led to a high-quality aesthetic and functional performance of the reconstruction obtained through two different flaps. More specifically, the fibular free flap for bone reconstruction allows a two-team approach and maintains an excellent vascularization, even in case of several osteotomies for the maxillary reconstruction as reported. In addition, the use of free radial forearm flap for soft tissue reconstruction permits to obtain long caliber vessels, thus facilitating surgery without repositioning of the patient during surgery and therefore, consequently reducing surgery times. Full article