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8 pages, 5489 KB  
Case Report
Successful Endourological Management of Encrusted Metallic Ureteral Stents: A Case-Series of Three Patients
by Georgios-Eleftherios Anagnostopoulos, Theodoros Spinos, Vasileios Tatanis, Angelis Peteinaris, Evangelos Liatsikos and Panagiotis Kallidonis
Reports 2026, 9(3), 206; https://doi.org/10.3390/reports9030206 (registering DOI) - 29 Jun 2026
Abstract
Background and Clinical Significance: Metallic stents represent a breakthrough in the treatment of ureteric obstruction, improving patient quality of life. Despite their advantages, management of encrustation remains a difficult complication to address. This case series highlights the rare occurrence of permanent ureteral [...] Read more.
Background and Clinical Significance: Metallic stents represent a breakthrough in the treatment of ureteric obstruction, improving patient quality of life. Despite their advantages, management of encrustation remains a difficult complication to address. This case series highlights the rare occurrence of permanent ureteral Wallstents remaining indwelling for over 20 years. It emphasizes that the function of these older devices can be successfully preserved using minimally invasive techniques. Case Presentation: This case series details three patients, two males, aged 75 and 69 years, diagnosed with colon cancer, and one female, aged 67 years, with cervical cancer, who presented with obstructive uropathy due to extrinsic malignant compression. As a therapeutic strategy, permanent ureteral Wallstents were placed in all three patients. Over time, the stents developed significant encrustation, leading to secondary obstruction. Clinical manifestations of this complication varied, ranging from asymptomatic hydronephrosis to acute symptomatic uropathy characterized by fever and localized pain. All cases were treated endoscopically with Ho:YAG laser lithotripsy, and urine flow was successfully restored. During the follow-up period, one patient experienced two recurrences that were managed with the same technique, another remained completely symptom-free, and the third was lost to long-term follow-up. Remarkably, the stents have remained functional for over 20 years post-implantation. Conclusions: This is a rare report documenting permanent ureteral Wallstents with such prolonged indwelling time. Furthermore, our findings suggest that through minimally invasive techniques, the function of these devices can be successfully preserved. Full article
(This article belongs to the Special Issue When Urology Surprises: Educational and Rare Clinical Cases)
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9 pages, 1127 KB  
Systematic Review
Characterizing Gynecological Cancers with the Uncommon dMMR/MSS Phenotype in Lynch Syndrome Patients
by Georgios Koktsidis, Davide Mauri, Stylianos Elemes, Emmanouil Saloustros, Genovefa Polychronidou, Georgios Lazaridis, Dimitrios Dionysopoulos, Anna Papaioannou and Eleni T. Timotheadou
J. Clin. Med. 2026, 15(13), 4979; https://doi.org/10.3390/jcm15134979 - 26 Jun 2026
Viewed by 128
Abstract
Background/Objectives: Lynch syndrome is an inherited autosomal dominant disease that predisposes to a broad spectrum of malignancies. This condition is driven by a germline pathogenic variant in one or more of the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2, EPCAM) that results [...] Read more.
Background/Objectives: Lynch syndrome is an inherited autosomal dominant disease that predisposes to a broad spectrum of malignancies. This condition is driven by a germline pathogenic variant in one or more of the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2, EPCAM) that results in genomic microsatellite instability (MSI-high). However, microsatellite-stable (MSS) tumors in Lynch syndrome patients may occur, but the relevant literature is scant. Our aim is to systematically identify, organize, and characterize the comprehensive available literature for Lynch syndrome-associated gynecological cancers (vulvar, vaginal, cervical, ovarian, endometrial) exhibiting a dMMR/MSS phenotype. Methods: Systematic review of the literature. Three medical databases, major related conferences and relevant oncology journals were scrutinized for relative evidence. Results: Eleven reports were identified comprising 2351 patients, 774 had confirmed Lynch syndrome (LS), of whom MSI results were available for 299 patients. In total, 130 patients developed LS-associated gynecological cancers, for whom MSI results were available. Among them, 36 tumors (27.7%) exhibited a dMMR/MSS molecular phenotype (23 endometrial, 12 ovarian, one synchronous endometrial–ovarian). No data for vulvar, vaginal, or cervical cancers were found. For dMMR/MSS endometrial cancers, the mean age at diagnosis was 50.5 years (range 36–62). dMMR/MSS tumors arose predominantly in MSH6 and, to a lesser extent, PMS2 carriers. No data on selective response to immune checkpoint inhibitors treatment were available. Conclusions: Lynch syndrome-associated gynecological cancers with dMMR/MSS phenotype are strongly underrepresented in the literature. Endometrial and ovarian cancers with dMMR/MSS phenotype are early onset and arise in a small proportion of patients. Better characterization is demanding to unearth whether response to immunotherapy treatment vary across Lynch dMMR/MSS and dMMR/MSI-High phenotypes. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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14 pages, 484 KB  
Article
Evaluation of Human and Viral Methylation, in Addition to Partial Genotyping, for a Molecular Triage Strategy in Women Under Active Surveillance for CIN2
by Silvia Gori, Helena Frayle, Alessio Pagan, Marika Soldà, Cesare Romagnolo, Egle Insacco, Licia Laurino, Mario Matteucci, Giuseppe Sordi, Enrico Busato, Manuel Zorzi, Tiziano Maggino and Annarosa Del Mistro
Cancers 2026, 18(13), 2067; https://doi.org/10.3390/cancers18132067 - 25 Jun 2026
Viewed by 158
Abstract
Background/Objective: Cervical intraepithelial neoplasia grade 2 (CIN2) shows heterogeneous clinical behavior, with substantial rates of spontaneous regression under active surveillance. Reliable molecular biomarkers are needed to distinguish regressive from transforming lesions and reduce overtreatment. We evaluated the prognostic role of host and [...] Read more.
Background/Objective: Cervical intraepithelial neoplasia grade 2 (CIN2) shows heterogeneous clinical behavior, with substantial rates of spontaneous regression under active surveillance. Reliable molecular biomarkers are needed to distinguish regressive from transforming lesions and reduce overtreatment. We evaluated the prognostic role of host and viral DNA methylation, alone and combined with HPV genotyping, in predicting CIN2 regression. Methods: This subanalysis derives from a prospective, multicenter Italian cohort of women with histologically confirmed CIN2 managed conservatively. Among 319 enrolled women, 134 with single HPV infections and valid host (FAM19A4/miR124-2) and viral (HPV L1 region) methylation results were included. HPV genotyping was performed with partial stratification (HPV16/18 vs. non-16/18). Clinical outcomes at 24 months were classified as regression versus persistence/progression. Logistic regression models assessed associations between biomarkers and regression. Results: At 24 months, 50% of women showed regression. Host and viral methylation positivity rates were more frequent in non-regressive lesions (40.3% vs. 19.4%, p = 0.01, and 52.2% vs. 32.8%, p = 0.02, respectively). Negative host methylation was significantly associated with regression (Odds Ratio OR = 0.37, 95% CI 0.17–0.81, p = 0.02), as was negative viral methylation (OR = 0.47, 95% CI 0.23–0.96, p = 0.04). Conclusions: Both host and viral methylation are inversely associated with CIN2 regression. Combining methylation markers did not substantially improve predictive accuracy; however, methylation negativity emerged as a potential molecular reassurance marker. When integrated with HPV genotyping, the highest probability of regression was observed among women with non-HPV16/18 infections and negative methylation results. These results endorse DNA methylation testing as a molecular tool for the conservative management of CIN2. Full article
(This article belongs to the Special Issue Molecular Markers and Targets in Modern Gynecologic Oncology)
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27 pages, 6152 KB  
Article
Phytochemical Profiling and Multitargeted Biological Activities of Crinum asiaticum L. var. anomalum Baker Leaf: In Vitro and In Silico Insights
by Tue Minh Duong, Son Hoang Nguyen, Kiep Minh Do, Tran Thanh Men, Kenji Kanaori and Kaeko Kamei
Plants 2026, 15(13), 1957; https://doi.org/10.3390/plants15131957 - 25 Jun 2026
Viewed by 195
Abstract
This study investigates the phytochemical and pharmacological profiles of Crinum asiaticum L. var. anomalum Baker from Vietnam. Phytochemical screening identified diverse secondary metabolites, including polyphenols, flavonoids, and alkaloids. Gas chromatography–mass spectrometry analysis of the n-hexane fractions revealed 19 major compounds. While all [...] Read more.
This study investigates the phytochemical and pharmacological profiles of Crinum asiaticum L. var. anomalum Baker from Vietnam. Phytochemical screening identified diverse secondary metabolites, including polyphenols, flavonoids, and alkaloids. Gas chromatography–mass spectrometry analysis of the n-hexane fractions revealed 19 major compounds. While all extracts showed moderate antioxidant activity, the chloroform fraction exhibited superior antidiabetic potential via α-amylase inhibition (IC50 = 83.13 ± 6.67 µg/mL). Furthermore, at non-cytotoxic concentrations (3.13 to 50 µg/mL), this fraction effectively rescued mouse β-TC6 insulinoma cells from thapsigargin. In anti-inflammatory assays, the n-hexane fraction significantly suppressed nitric oxide production in RAW 264.7 macrophages (IC50 = 53.12 ± 1.63 µg/mL). Notably, the extracts displayed remarkable selective anticancer activity, particularly the chloroform fraction against HeLa cervical and HepG2/Huh-7 hepatoma cell lines. In silico ADMET and Lipinski’s Rule of Five analyses confirmed that the key bioactive constituents possess favorable pharmacokinetic profiles and drug-likeness. These findings demonstrate C. asiaticum L. var. anomalum Baker as a promising natural source for developing multitarget therapeutic agents against inflammation, diabetes, and cancer. Full article
(This article belongs to the Section Phytochemistry)
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20 pages, 335 KB  
Review
Para-Aortic Lymph Node Staging and Oncologic Outcomes in Locally Advanced Cervical Cancer: A Narrative Review
by Juan Sebastián Obando-Rodríguez, Santiago Vieira-Serna, Jonathan Peralta, Juliana Rodríguez, Erick Estrada, Luisa López-Saldarriaga, Gabriel Levin and Rene Pareja
Cancers 2026, 18(13), 2058; https://doi.org/10.3390/cancers18132058 - 25 Jun 2026
Viewed by 353
Abstract
Background: Para-aortic lymph node involvement is present in approximately 17–24% of women with locally advanced cervical cancer (LACC) and is one of the strongest adverse prognostic factors in this population. Current international guidelines recommend two alternative staging techniques: the International Federation of [...] Read more.
Background: Para-aortic lymph node involvement is present in approximately 17–24% of women with locally advanced cervical cancer (LACC) and is one of the strongest adverse prognostic factors in this population. Current international guidelines recommend two alternative staging techniques: the International Federation of Gynecology and Obstetrics (FIGO) and European Society of Gynecologic Oncology (ESGO) endorse imaging-based staging as the primary method to define radiation fields, whereas the National Comprehensive Cancer Network (NCCN) lists pre-treatment minimally invasive para-aortic lymphadenectomy as a Category 2B recommendation. Objective: We aimed to review and critically appraise the available evidence on the oncologic impact (progression-free and overall survival) of pre-treatment surgical para-aortic staging compared with clinical imaging-based staging in women with LACC. Methods: We searched MEDLINE (Ovid), Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and Scopus from inception to January 2026, complemented by manually searching the reference lists for relevant articles and prior reviews. The review focused on comparative studies of women with LACC of squamous, adenocarcinoma, or adenosquamous histology—operationally defined as FIGO 2009 stages IB2–IVA with pelvic nodal involvement or FIGO 2018 stages IB3–IVA who received definitive-intent radiotherapy with or without concurrent chemotherapy and brachytherapy, and for whom comparative survival outcomes between a surgical-staging arm and an imaging-staging arm were reported. For this manuscript, a narrative review style was planned and reported in line with SANRA (Scale for the Assessment of Narrative Review Articles) quality criteria. Results: Twelve studies were included: two randomized controlled trials and ten observational studies (nine retrospective cohorts and one population-based analysis). Surgical staging consistently increased detection of occult para-aortic disease and led to more frequent use of extended-field radiotherapy (18–44%), but it did not yield a reproducible advantage in terms of progression-free or overall survival over imaging-guided chemoradiation. Conclusions: In LACC, pre-treatment surgical para-aortic staging improves anatomic and prognostic information but has not shown a consistent survival advantage over imaging-based staging combined with contemporary chemoradiation. Current comparative evidence does not support routine surgical staging, and its use still warrants further prospective evaluation in large clinical trials. Until results from ongoing phase III trials are available, surgical staging should be considered an individualized option in highly selected cases within multidisciplinary decision-making at experienced clinical centers. Full article
(This article belongs to the Special Issue Novel Approaches in the Management of Gynecological Cancers)
29 pages, 308 KB  
Article
Facilitators and Barriers to Implementing Evidence-Based Clean Intermittent Catheterization After Radical Hysterectomy: A Mixed-Methods Study
by Lu Xing, Biru Luo, Yuqing Song, Huaping Fu, Wen Zhao and Xue Deng
J. Clin. Med. 2026, 15(13), 4925; https://doi.org/10.3390/jcm15134925 - 24 Jun 2026
Viewed by 119
Abstract
Objective: To analyze the perceived facilitators and barriers promoting and hindering the clinical application of the best evidence of clean intermittent catheterization (CIC) in patients after radical hysterectomy (RH). Methods: This study employed a convergent parallel mixed-methods design. Participants included patients undergoing CIC [...] Read more.
Objective: To analyze the perceived facilitators and barriers promoting and hindering the clinical application of the best evidence of clean intermittent catheterization (CIC) in patients after radical hysterectomy (RH). Methods: This study employed a convergent parallel mixed-methods design. Participants included patients undergoing CIC after RH, medical and nursing practitioners and managers in the gynecological department and outpatient clinics at a tertiary-level women’s and children’s hospital in Chengdu. They were included in both components separately. Interview data were managed using Nvivo 11.0 software and analyzed through directed content analysis. Quantitative data were analyzed using SPSS 29.0 statistical software. Results: A questionnaire survey was conducted among 156 healthcare providers and 300 patients. Qualitative interviews were conducted with 11 healthcare workers and 12 patients. At the evidence itself level, evidence meeting clinical needs and evidence lacking practical applicability, respectively, promoted and hindered clinical implementation of the best evidence. At the potential adopters’ level, healthcare professionals’ insufficient professional competence, low willingness to promote implementation, numerous concerns, and lack of autonomy and awareness regarding the importance of the task were significant barriers, but they maintained an overall positive attitude toward the application. At the practical environment level, patient-related perceived barriers predominantly hindered evidence implementation. Additionally, a supportive practice atmosphere, economic feasibility, and talent development opportunities served as key facilitators. However, existing nursing practice content and workflows directly impacted evidence adoption. Conclusions: The promotion and barriers to the clinical application of the best evidence for CIC in RH postoperative patients are multifaceted. Targeted intervention strategies must be developed to facilitate the effective translation of evidence into clinical practice. Full article
(This article belongs to the Section Nephrology & Urology)
22 pages, 1994 KB  
Article
Naphthoquinone-Amino Acids Regulate Cellular Cancer Associated Processes, p53 and miR-34a-5p Expression in Immortal and Tumorigenic Cervical Cell Lines
by Jessica Lizbeth Sifuentes-Padilla, Angelica Judith Granados-López, Antonia Monserrat Campos-Lujan, Abel Suárez-Castro, Mayra Denise Herrera, Yamilé López-Hernández, Hiram Hernández-López, José Antonio Varela-Silva, Rosalinda Gutiérrez-Hernández, Claudia Araceli Reyes-Estrada, Sergio Hugo Sánchez-Rodríguez, Ernesto Rivera-Ávalos, Denisse de Loera and Jesús Adrián López
Int. J. Mol. Sci. 2026, 27(13), 5703; https://doi.org/10.3390/ijms27135703 - 24 Jun 2026
Viewed by 98
Abstract
Cervical cancer is a malignant disease that affects women worldwide and is associated with both high incidence and a high mortality rate. miR-34 is a direct transcriptional-target of p53 and is downregulated in several types of cancers. 1,4-Naphthoquinones (NQs) have anticancer properties and [...] Read more.
Cervical cancer is a malignant disease that affects women worldwide and is associated with both high incidence and a high mortality rate. miR-34 is a direct transcriptional-target of p53 and is downregulated in several types of cancers. 1,4-Naphthoquinones (NQs) have anticancer properties and have been used to modulate miR-34 expression. We tested (3-chloro-NQ-2-yl)-alanine (ANQCl), -methionine (MNQCl), -glycine (GNQCl), -phenylalanine (FNQCl), -asparagine (NNQCl), and (1,4-napthoquinon-2-yl)-asparagine (NNQ) in immortal and tumorigenic cells, both HPV-positive and -negative, simulating precancerous and cancerous status to observe the response of the p53-miR-34 system, migration and invasion. A dose–response was achieved to determine the IC50 of the compounds in SiHa, CaLo, C33-A and HaCaT cells. HaCaT cell migration inhibition was more potent than in SiHa, CaLo, and C33-A cells, while invasion hindrance was more evident in the tumorigenic SiHa, CaLo and C33-A. NNQCl, GNQCl, ANQCl and FNQCl compounds induced p53 overexpression in SiHa and CaLo cells. Compound ANQCl in SiHa and FNQCl in CaLo induced miR-34a overexpression, probably via p53. Migration and invasion of most compounds decreased independently of p53-miR-34. NQ-amino acids exert effect on cell proliferation, migration and invasion in cervical cancer cells, suggesting their potential use in the field of cancer treatment. Full article
(This article belongs to the Special Issue Recent Advances in Non-Coding RNAs in Human Research)
17 pages, 5721 KB  
Article
Genetic Variation of HPV53 and the Identification of T-Cell Epitopes
by Li Wang, Sudan Jiao, Sihan Lan, Yuxiao Zhang, Jing Yu, Jie He, Hongping Zhang and Min Feng
Microorganisms 2026, 14(7), 1395; https://doi.org/10.3390/microorganisms14071395 - 24 Jun 2026
Viewed by 107
Abstract
Human papillomavirus type 53 (HPV53) is one of the most prevalent HPV genotypes in China, frequently detected in cervical intraepithelial neoplasia and cervical cancer, yet remains outside the coverage of all currently available prophylactic vaccines and is relatively understudied. This study performed a [...] Read more.
Human papillomavirus type 53 (HPV53) is one of the most prevalent HPV genotypes in China, frequently detected in cervical intraepithelial neoplasia and cervical cancer, yet remains outside the coverage of all currently available prophylactic vaccines and is relatively understudied. This study performed a comprehensive analysis of HPV53 clinical infection profiles, genomic diversity, and T-cell epitopes to inform therapeutic vaccine development. Clinical analysis of 158 HPV53-positive patients showed that infections were most prevalent in women aged 40–59 years, with persistent infection identified in 13.3% participants and a subset of cases associated with cervical lesions. Genomic analysis of 134 HPV53 isolates identified four lineages (A-D, with lineage D further subdivided into four sublineages, and an overall nucleotide variability of 4.4%. E2 was the most variable protein while E7 was the most conserved. Immunoinformatic prediction identified 176 HLA class I-restricted T-cell epitopes across E6, E7, E1, and E2, from which 20 candidates were selected for experimental validation. Ten demonstrated strong HLA binding affinity in vitro, and murine immunization identified a E6 peptide VYNFAYTDL as an immunodominant epitope. Three validated epitopes exhibited sequence overlap with 12 to 13 of other 13 high-risk HPV genotypes, suggesting their potential as broadly cross-reactive targets. These findings clarify the genomic diversity and immunogenic epitope landscape of HPV53, providing a foundation for the rational design of therapeutic vaccines. Full article
(This article belongs to the Special Issue The Latest Research on Human Papillomavirus)
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12 pages, 9158 KB  
Article
National Surveillance-Based Retrospective Ecological Longitudinal Analysis of Stroke Incidence Trends and Health-Screening Indicators in Korea, 2011–2023, with Model-Based Projections to 2028 Using National Health Insurance Service Data
by Hyeran Jung and Minsun Jung
Healthcare 2026, 14(13), 1815; https://doi.org/10.3390/healthcare14131815 - 23 Jun 2026
Viewed by 136
Abstract
Background: Stroke remains a leading cause of mortality, disability, and health-system burden in Korea’s rapidly aging population. We aimed to describe national stroke incidence trends from 2011 to 2023, characterize ecological associations between stroke incidence and health-screening indicators, and generate model-based projections [...] Read more.
Background: Stroke remains a leading cause of mortality, disability, and health-system burden in Korea’s rapidly aging population. We aimed to describe national stroke incidence trends from 2011 to 2023, characterize ecological associations between stroke incidence and health-screening indicators, and generate model-based projections through 2028 to support health-system planning. Methods: This retrospective ecological longitudinal analysis used three publicly available aggregate national data sources: (1) NHIS annual aggregate statistics on crude and age-standardized stroke incidence, stroke case counts, first-onset vs. recurrent stroke, and case-fatality rates (2011–2023); (2) regional standardized health-awareness survey rates for stroke symptoms, myocardial infarction symptoms, blood pressure, and blood glucose (2017–2025); and (3) national cancer-screening outcome tallies for breast and cervical cancer (2010–2024). All analyses used pre-aggregated annual summary data; individual-level NHIS records were not used. Annual trends were modeled with ordinary least-squares linear regression (n = 13 annual observations). Pearson correlations were computed only for overlapping observation windows. Model-based projections are presented with 95% prediction intervals and are explicitly distinguished from observed NHIS values. This study is purely descriptive and ecological; no causal inference is made. Results: Crude stroke incidence increased from 199.2 to 221.1 per 100,000 (2011–2023; slope +2.32/year, R2 = 0.83), whereas age-standardized incidence declined from 158.3 to 113.2 per 100,000 (slope −3.41/year, R2 = 0.96), a pattern consistent with demographic aging as a contributing factor to growing absolute burden, though formal age-decomposition analysis would be required to confirm this inference. Total cases increased from 99,837 to 113,098; the 30-day case-fatality rate declined from 8.5% to 7.5%. Ecological correlations showed that blood glucose awareness was strongly negatively correlated with age-standardized incidence (r = −0.944, p = 0.001, n = 7), though these are ecological associations and must not be interpreted as individual-level causal relationships. Model-based projections estimate crude incidence near 230.7 (95%PI 219.2–242.2) and age-standardized incidence near 103.2 (95%PI 95.7–110.8) per 100,000 by 2026. Conclusions: Concurrent increase in crude burden and decline in age-standardized incidence reflects demographic aging as the primary driver of Korea’s stroke burden. Projections support integrated cardiovascular prevention, public health education, and age-sensitive service planning. All projections are short-horizon statistical extrapolations intended for policy scenario planning only and must not be interpreted as observed future NHIS outcomes. Full article
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14 pages, 365 KB  
Article
Family Voices in Digital Patient Navigation for Cervical Cancer Care in Indonesia
by Hana Rizmadewi Agustina, Hartiah Haroen, Tuti Pahria, Gatot Nyarumenteng Adhipurnawan Winarno, Citra Windani Mambang Sari, Windy Natasya, Heni Nur Anina, Inggriane Puspita Dewi, Yovita Dwi Setiyowati, Diwa Agus Sudrajat, Sita Sharma, Chyntya Putri Alita and Finny Fauziah Hidayat
Healthcare 2026, 14(13), 1809; https://doi.org/10.3390/healthcare14131809 - 23 Jun 2026
Viewed by 182
Abstract
Background: Cervical cancer remains a significant health issue in Indonesia, where structural barriers, fragmented information, and sociocultural norms continue to hinder timely diagnosis and treatment. Families play a central role throughout the illness journey, yet their perspectives are often overlooked in the [...] Read more.
Background: Cervical cancer remains a significant health issue in Indonesia, where structural barriers, fragmented information, and sociocultural norms continue to hinder timely diagnosis and treatment. Families play a central role throughout the illness journey, yet their perspectives are often overlooked in the development of digital patient navigation systems. This study explored family experiences, caregiving challenges, and expectations for a family-centered digital navigation model, DIVA.ID, by integrating Digital Health frameworks and Family Systems Theory. Methods: A qualitative descriptive approach was employed through semi-structured, in-depth interviews with 18 purposively selected family caregivers of women with cervical cancer at a major referral hospital in West Java. Participants were selected because they were directly involved in daily care, treatment decisions, logistical support, or emotional assistance. Interviews were conducted between August and October 2025 and continued until thematic saturation was reached, as indicated by repetition of categories and the absence of new major codes in the final interviews. Data were analyzed using inductive–deductive content analysis guided by Elo and Kyngäs, with five researchers conducting independent coding, iterative code comparison, consensus meetings, and theoretical mapping. Results: Four main themes emerged: (1) family involvement in decision-making, including collective discussion, shifting authority roles, and patient autonomy; (2) caregiver burden, involving physical exhaustion, psychological distress, social restriction, stigma, financial pressure, and employment disruption; (3) psycho-spiritual coping mechanisms, including emotional sharing, prayer, crying, patience, and surrender to God; and (4) digital healthcare needs, covering BPJS guidance, treatment information, scheduling, communication pathways, shelter support, and mental–spiritual support. Mapping these themes to Digital Health frameworks and Family Systems Theory clarified how DIVA.ID could translate family experiences into practical navigation functions. Conclusions: This study provides empirical foundations for a culturally sensitive, family-centered digital navigation model in Indonesia. Rather than demonstrating effectiveness, the findings identify design requirements for DIVA.ID that should be tested in subsequent feasibility, usability, and intervention studies. Full article
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18 pages, 447 KB  
Article
Five-Year Risk of CIN3+ After CIN1 Biopsy in a Norwegian Screening Setting: Comparison of CIN1 Diagnosed in a Single Calendar Year and in Two Consecutive Calendar Years
by Sveinung Wergeland Sørbye, Mona Antonsen and Elin Richardsen
Pathogens 2026, 15(6), 657; https://doi.org/10.3390/pathogens15060657 - 22 Jun 2026
Viewed by 119
Abstract
Cervical intraepithelial neoplasia grade 1 (CIN1) is usually managed conservatively, but uncertainty remains about the subsequent risk of clinically significant high-grade disease, particularly after repeated CIN1. We conducted a retrospective population-based cohort study using anonymized cervical cytology, HPV, and histopathology records from Northern [...] Read more.
Cervical intraepithelial neoplasia grade 1 (CIN1) is usually managed conservatively, but uncertainty remains about the subsequent risk of clinically significant high-grade disease, particularly after repeated CIN1. We conducted a retrospective population-based cohort study using anonymized cervical cytology, HPV, and histopathology records from Northern Norway from 2011 to 2025. We described temporal trends in screening-related outcomes and estimated the 5-year risk of CIN3+ after histologically confirmed CIN1 diagnosed in a single calendar year or in two consecutive calendar years. Across 2011–2025, the annual datasets comprised 334,471 screening records; 35,796 had ASC-US+ cytology (10.7%), 29,723 had a positive HPV test (8.9%), 35,416 underwent biopsy (10.6%), and 7870 were diagnosed with CIN2+ (2.4%). HPV positivity increased from 0.9% in 2011 to 15.7% in 2025, whereas CIN2+ detection peaked at 3.1% in 2018 and declined to 1.8% in 2025. In person-based analyses, the 5-year risks after CIN1 diagnosed in a single calendar year versus two consecutive calendar years were 4.3% versus 3.4% for CIN3+, 0.2% versus 0.1% for cervical cancer, and 15.4% versus 14.3% for CIN2+. Repeated CIN1 was not associated with higher subsequent CIN3+ risk, supporting conservative, risk-based follow-up after CIN1 biopsy. Full article
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33 pages, 4245 KB  
Review
Phytochemistry, Bioavailability, and Molecular Mechanisms Underlying Multitarget Anticancer Activity of Aloe vera
by Nimra Haroon, Adnan Amjad, Muhammad Maaz, Ahmad Mujtaba Noman, Nimra Anees, Zafarullah Muhammad, Mohibullah Shah and Waleed Al Abdulmonem
Nutrients 2026, 18(12), 2034; https://doi.org/10.3390/nu18122034 - 22 Jun 2026
Viewed by 373
Abstract
Background/Objectives: Cancer, a multifactorial disease with uncontrolled cell growth, oxidative stress, inflammation, genomic instability, and molecular signaling pathways, is a global health concern, leading to the ~20 million newly diagnosed cases annually. Although conventional therapy has been shown to enhance the survival [...] Read more.
Background/Objectives: Cancer, a multifactorial disease with uncontrolled cell growth, oxidative stress, inflammation, genomic instability, and molecular signaling pathways, is a global health concern, leading to the ~20 million newly diagnosed cases annually. Although conventional therapy has been shown to enhance the survival rates of cancer patients, its clinical efficacy is limited by certain side effects that occur as a result of treatment, thus necessitating the exploration of plant-derived bioactive compounds for their potential as safer and alternative supportive therapeutic agents. Aloe vera, known as the plant of immortality, comprises phytochemicals, such as anthraquinones (aloe-emodin, emodin, and aloin), polysaccharides (acemannan), flavonoids, and phenolic acids, which contribute to the pharmacological effect of the compound. Methods: This review summarizes the anticancer potential of Aloe vera, and the data were retrieved from databases, such as PubMed, Google Scholar, ScienceDirect, Web of Science, and Wiley Online Library, during the time period of 2015 to 2025. Results: The literature revealed that Aloe vera and its bioactive compounds have dose-dependent cytotoxic and anti-proliferative properties against hepatocellular, cervical, colorectal, lung, breast, prostate, and hematological cancers, which are significantly mediated by apoptosis and pyroptosis induction, reactive oxygen species (ROS) production, mitochondrial dysfunction, inhibition of angiogenesis and metastasis, and the modulation of key signaling pathways, particularly PI3K/Akt, MAPK, NF-кB, p53, and Wnt/β-catenin. Furthermore, anthraquinones, including Aloe-emodin, demonstrate potent anticancer effects at micro-molar doses, and polysaccharides increase immune reactions and provide tumor immunity. Conclusions: Conclusively, Aloe vera is a promising multi-target natural compound, particularly efficient in the treatment of cancer. However, despite significant therapeutic potential, more research on pharmacokinetics, standard dose, and controlled clinical trials of Aloe vera is required to validate clinical applicability. Full article
(This article belongs to the Section Phytochemicals and Human Health)
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17 pages, 838 KB  
Systematic Review
Beyond HPV in Eastern Europe: Genotype Distribution, Molecular Biomarkers, Vaginal Microbiome, and Implications for Cervical Cancer Prevention
by Eugenia-Alina Radu, Corina-Ioana Anton, Cristian-Sorin Sima and Adrian Streinu-Cercel
Life 2026, 16(6), 1039; https://doi.org/10.3390/life16061039 - 22 Jun 2026
Viewed by 173
Abstract
Human papillomavirus (HPV) infection remains the principal etiological factor in cervical cancer development worldwide, with Eastern Europe continuing to demonstrate disproportionately high cervical cancer incidence and mortality rates. Regional disparities in screening implementation, vaccination coverage, and HPV genotype distribution contribute substantially to the [...] Read more.
Human papillomavirus (HPV) infection remains the principal etiological factor in cervical cancer development worldwide, with Eastern Europe continuing to demonstrate disproportionately high cervical cancer incidence and mortality rates. Regional disparities in screening implementation, vaccination coverage, and HPV genotype distribution contribute substantially to the persistent burden of HPV-related disease. In recent years, increasing attention has focused on molecular biomarkers and the vaginal microbiome as complementary approaches for improving cervical cancer prevention strategies. This systematic review aimed to evaluate recent evidence regarding HPV genotype distribution, molecular biomarkers, vaginal microbiome composition, and their implications for cervical cancer prevention in Eastern Europe. A systematic literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, Embase, and the Cochrane Library for studies published between January 2020 and May 2026. This systematic review was conducted in accordance with the PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420261391136). Studies from Eastern European populations reporting data on HPV genotype distribution, screening strategies, vaccination, molecular biomarkers, or vaginal microbiome composition were included. HPV prevalence in screening populations ranged from approximately 12% to over 20%, with HPV16 consistently identified as the predominant genotype across all included studies. However, non-16/18 high-risk genotypes, particularly HPV31, HPV51, HPV52, HPV66, and HPV68, represented a substantial proportion of infections in several Eastern European cohorts. Studies evaluating CINtec PLUS cytology and HPV E6/E7 mRNA testing demonstrated improved specificity for identifying clinically significant cervical lesions compared with HPV DNA testing alone. Emerging evidence also suggested associations between vaginal dysbiosis, increased microbial diversity, persistent high-risk HPV infection, and progression to cervical intraepithelial neoplasia. Although the 9-valent HPV vaccine provides coverage for most circulating high-risk genotypes identified in the region, vaccination uptake remains inconsistent throughout Eastern Europe. The findings of this systematic review support the growing importance of extended HPV genotyping, molecular biomarkers, and microbiome-related approaches in cervical cancer prevention strategies in Eastern Europe. Strengthening organized screening programs, expanding vaccination coverage, and improving access to molecular diagnostic technologies remain essential priorities for reducing the regional burden of HPV-related disease. Full article
(This article belongs to the Section Physiology and Pathology)
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27 pages, 3712 KB  
Review
When Breast Cancer Meets the Uterus: A Quantitative Review of 105 Cases Spanning Four Decades
by Tiberiu Augustin Georgescu, Antonia Carmen Georgescu and Maria Victoria Olinca
Medicina 2026, 62(6), 1205; https://doi.org/10.3390/medicina62061205 - 22 Jun 2026
Viewed by 229
Abstract
Background and Objectives: Uterine metastasis from breast carcinoma is rare but poses substantial diagnostic and therapeutic challenges. Invasive lobular carcinoma (ILC) demonstrates a documented predilection for unusual metastatic patterns including the female genital tract, while tamoxifen-associated endometrial pathology may complicate diagnosis in breast [...] Read more.
Background and Objectives: Uterine metastasis from breast carcinoma is rare but poses substantial diagnostic and therapeutic challenges. Invasive lobular carcinoma (ILC) demonstrates a documented predilection for unusual metastatic patterns including the female genital tract, while tamoxifen-associated endometrial pathology may complicate diagnosis in breast cancer survivors. Materials and Methods: We performed a structured PubMed/MEDLINE and Google Scholar search (1980–2025) for cases with histologically confirmed breast primary and uterine involvement; a pooled analysis of demographic, histological, molecular, and clinical variables was performed. Results: 105 individual cases were identified. ILC accounted for 58.0% of histologically classified cases despite representing only 10–15% of breast cancers. Endometrial involvement was present in 68.6%, myometrial in 25.7%, and cervical in 26.7%. Tamoxifen exposure was strongly associated with polyp-substrate metastasis (29.3% vs. 4.7%; Fisher’s exact p = 0.0009; OR 8.41, 95% CI 2.20–32.14). Abnormal uterine bleeding was the dominant presentation (68.1%); 19.8% were asymptomatic. Median latency was 36 months (range from 24 months before to 360 months after the breast cancer diagnosis). Conclusions: Uterine metastasis from breast carcinoma is dominated by invasive lobular histology and frequently involves tamoxifen-associated polyps. A combined immunohistochemical panel (GATA3, TRPS1, E-cadherin, hormone receptors, PAX8) is essential for distinguishing metastatic disease from primary uterine pathology. Endometrial sampling should be considered with a low threshold in breast cancer survivors with abnormal uterine bleeding, and breast imaging is warranted when discohesive cells are encountered without a known breast primary. These proportions describe the published case literature rather than population-based prevalence; because the evidence is limited to case reports and small series, they should not be read as the true frequency of uterine involvement among women with breast cancer. Full article
(This article belongs to the Section Obstetrics and Gynecology)
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31 pages, 1326 KB  
Review
Bidirectional Interactions Between Cervicovaginal Microbiota and Human Papillomavirus Drive Persistence and Disease Progression
by Daniel Osmar Suárez-Rico, Lourdes del Carmen Rizo de la Torre, Martin Zermeño-Ruiz, Luis Ricardo Balleza-Alejandri, Jesús Jonathan García-Galindo, Héctor Montoya-Fuentes and Alberto Beltrán-Ramírez
Int. J. Mol. Sci. 2026, 27(12), 5616; https://doi.org/10.3390/ijms27125616 - 22 Jun 2026
Viewed by 152
Abstract
Persistent high-risk human papillomavirus infection is a critical prerequisite for cervical intraepithelial neoplasia and cervical cancer, yet viral factors alone do not fully explain why most infections clear while a subset persists and progresses. Emerging longitudinal, multi-omics, and mechanistic evidence supports a plausible [...] Read more.
Persistent high-risk human papillomavirus infection is a critical prerequisite for cervical intraepithelial neoplasia and cervical cancer, yet viral factors alone do not fully explain why most infections clear while a subset persists and progresses. Emerging longitudinal, multi-omics, and mechanistic evidence supports a plausible model in which the cervicovaginal microbiota is not a passive bystander but a functional determinant of mucosal immunity, epithelial barrier integrity, and local metabolic tone. Lactobacillus-dominant community states, particularly those enriched in Lactobacillus crispatus, are generally associated with lower pH, regulated inflammatory signaling, stronger barrier function, and a higher likelihood of HPV clearance. In contrast, anaerobe-enriched dysbiosis is linked to elevated pro-inflammatory cytokines, altered antigen presentation, immune checkpoint signatures consistent with T-cell dysfunction, and metabolic shifts involving lactate depletion and accumulation of short-chain fatty acids and other metabolites that can influence epithelial and immune-cell programs. Importantly, the interaction is bidirectional: hrHPV can remodel the microenvironment by suppressing host defense peptides and perturbing mucosal barriers, thereby reducing Lactobacillus fitness and reinforcing dysbiosis in a feed-forward loop that favors persistence and oncogenic progression. This review integrates functional ecology, longitudinal clinical evidence, immunological and metabolic mechanisms, and translational implications, highlighting opportunities for microbiome-informed risk stratification and adjunctive interventions, as well as key gaps requiring standardized longitudinal multi-omics and rigorously designed clinical trials. Full article
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