Cancer Biology & Medicine最新文献

Objective: Cervical cancer remains a global health challenge with substantial disparities between countries. High-quality colposcopy is essential for cervical cancer prevention, yet training opportunities remain inadequate worldwide. We developed the Intelligent Digital Education Tool for Colposcopy (iDECO) to address training gaps and evaluated the effect across diverse international settings.

Methods: Six pre-post interventional training programmes were conducted in China, Mexico, and Mongolia from December 2024 to May 2025. A total of 369 trainees from 87 centers participated in a 3-week online training programme using iDECO, a bilingual web-based platform featuring authentic colposcopy cases, gamified learning pathways, and personalized analytics. The primary outcomes included colposcopy competence in general assessment, colposcopic findings, diagnostic accuracy, and management decisions. The secondary outcomes focused on participant feedback and satisfaction.

Results: Of 369 participants who completed pretests, 333 (90.24%) completed post-training assessments. Significant improvements were observed across all competency domains. Diagnostic accuracy increased with an odds ratio (OR) of 1.72 (95% CI: 1.60-1.86) with the greatest gains in high-grade lesion identification [OR = 2.27 (95% CI: 1.94-2.64)]. Squamocolumnar junction visibility and transformation zone type assessments improved with ORs of 1.41 (95% CI: 1.31-1.51) and 1.87 (95% CI: 1.73-2.01), respectively. Biopsy decision-making accuracy also showed significant improvement [OR = 2.09 (95% CI: 1.91-2.29)]. International participants showed lower baseline performance but achieved the greatest improvements. Greater than 85% of participants rated the training highly satisfactory and 83.56% preferred intelligent training over traditional methods.

Conclusions: iDECO-based training significantly improved colposcopy competence across diverse international settings with high user satisfaction. These findings support the potential for worldwide implementation of intelligent digital training tools to address colposcopy training gaps and contribute to the elimination of cervical cancer.

Objective: Cervical cancer caused by persistent high-risk human papillomavirus (hrHPV) infection remains a leading cause of cancer-related mortality in women. As prophylactic HPV vaccines cannot eliminate existing infections, developing therapeutic vaccines targeting HPV E6/E7 oncoproteins is critical for reversing precancerous lesions. This study aimed to design a novel multi-epitope vaccine against HPV16, incorporating newly identified immunodominant epitopes and evaluating the therapeutic efficacy.

Methods: The multi-epitope vaccine HSP70-12P was bioinformatically designed to include cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) epitopes from HPV16 E6/E7, which were fused to the C-terminal domain (residues 359-610) of Mycobacterium tuberculosis HSP70 as an adjuvant. Two formulations were used, as follows: (1) protein-based Pro-HSP70-12P; and (2) DNA-based DNA-HSP70-12P. Therapeutic efficacy was evaluated in TC-1 tumor-bearing mouse models. Tumor regression, survival rates, and immune correlates (T cell responses and cytokine profiles) were assessed. Immunodominant epitopes were identified using ELISpot.

Results: The Pro-HSP70-12P protein vaccine induced strong immune responses and provided lasting antitumor protection. The vaccine activated cell-mediated immunity and stimulated effector memory T cells in the HPV-16-related tumor mouse model, resulting in strong tumor clearance effects. Pro-HSP70-12P demonstrated superior performance compared to the DNA-HSP70-12P vaccine, achieving complete regression of small tumors (diameter < 2 mm) with a single dose and conferring long-lasting protection in TC-1 rechallenge experiments. Three novel immunodominant epitopes were identified (E6-38-45, E6-124-132, and E7-50-57). The E6 epitopes address a critical gap in E6-targeted vaccine design.

Conclusions: The multi-epitope protein vaccine, Pro-HSP70-12P, represents a potent therapeutic candidate against HPV-driven malignancies, which has the capacity to induce tumor regression and long-term immunity. These findings support further clinical development.

Objective: Drawbacks of human papillomavirus (HPV) primary screening, including high referral rates and low specificity, highlight the necessity for triage strategies to balance the screening benefits with potential harms.

Methods: A cross-sectional, population-based diagnostic study was conducted in rural Xinjiang, China involving 8,638 women ≥ 25 years of age who participated in organized cervical cancer screening between 2023 and 2024. The study evaluated the accuracy and efficiency of multiple HPV-based "screen-triage" strategies. Histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+ and CIN3+) served as disease outcomes.

Results: Among single-step triage strategies, only extended genotyping for the seven most carcinogenic HPV types (HPV16/18/31/33/45/52/58) maintained sensitivity for CIN2+ comparable to HPV screening without triage (90.0% vs. 92.5%, P = 0.50) but significantly improved specificity (94.7% vs. 90.8%, P < 0.001). This approach led to a 38% reduction in colposcopy referrals (relative rate, 0.62; 95% CI: 0.59-0.65). Two-step triage algorithms (HPV16/18 with reflex ASC-US+ or methylation) showed slightly lower but non-significant sensitivity (87.5%, P = 0.13/89.6%, P =0.50) than HPV primary screening without triage, yet achieved significantly increased specificity (> 95%, P < 0.001) and reduced colposcopy referral by ~50% (relative rate, 0.5; P < 0.001). If negative for cytology or methylation, women positive for 12 high-risk HPV types (excluding HPV16/18) had a < 2% risk of CIN2+ (CIN3+ risk < 1%), indicating delayed follow-up.

Conclusions: Focusing on the seven high-risk HPV types within a one-step "screen-triage" framework effectively balances minimal sensitivity loss with significant gains in specificity, reducing unnecessary referrals and treatments, especially valuable in resource-limited settings. Integrating HPV genotyping with methylation results improves the accurate identification of women requiring immediate referral, which is advisable when resources allow.

Objective: Cervical cancer is a growing concern in China, especially among women who reside in rural areas and older women. Understanding age- and region-specific trends in cervical cancer is vital for informing policy and assessing progress toward WHO elimination targets.

Methods: The 2000-2020 data from 22 long-standing registries contributing to the China national cancer registry was analyzed to estimate age-standardized incidence and mortality rates (ASIR and ASMR, respectively). Joinpoint regression yielded an average annual percentage change (AAPC) stratified by age group (<35, 35-64, 65-74, and ≥75 y) and by urban-rural area. The comparative analysis included GLOBOCAN Overtime data from selected Asia-Pacific countries.

Results: The ASIR tripled in China between 2000 and 2020 before stabilizing (AAPC = 6.5%), while the ASMR rose steadily (AAPC = 3.9%). The urban incidence declined after 2009 among women <35 y, while rural trends were broadly stable. The ASIR and ASMR increased in urban areas among women 35-64 y of age, while rural areas had a rising ASIR and a stable ASMR, suggesting potential screening effects. In contrast, women ≥65 y of age had a steadily increasing incidence and mortality in rural and urban areas. Australia and Republic of Korea had consistent declines in the ASIRs and ASMRs compared to other Asia-Pacific countries, whereas Japan exhibited rising trends. The Philippines experienced a surge in mortality rates, despite incidence rates remaining stable or declining.

Conclusions: The cervical cancer burden in China has begun to plateau but large disparities persist by age and geography. To achieve elimination of cervical cancer, it is imperative to implement tailored strategies that prioritize the urgent expansion of HPV vaccination programs, the deployment of high-efficacy screening methods, and the universal access to treatment throughout the nation.

Malignant tumors are a major threat to human health with the immune responses critically influenced by major histocompatibility complex (MHC) class I and II molecules. While MHC-I has been extensively studied for its role in tumor immunity, research on MHC-II, particularly MHC-II function within the tumor microenvironment, has lagged behind research on MHC-I. The expression and regulation of tumor-specific MHC-II (tsMHC-II) in tumor cells not only reflect the immunogenic landscape of the tumor microenvironment but also actively shape antitumor immune responses by modulating CD4⁺ T cell recognition and activation. Expression of tsMHC-II is tightly controlled by intrinsic oncogenic signaling and extrinsic cytokine stimulation, positioning tsMHC-II as a key determinant of response to immunotherapy, including immune checkpoint blockade. Accordingly, tsMHC-II may serve as a predictive biomarker and a potential therapeutic target in tumor immunotherapy. This review highlights recent advances in the structure and function of MHC-II, the MHC-II regulatory mechanisms in tumors, and the emerging significance of MHC-II in guiding future immunotherapeutic strategies.

Objective: CLT-003 is a novel phenylphthalimide derivative encapsulated in poly (lactate-glycolic acid) copolymer nanoparticles using nanotechnology techniques. CLT-003 possesses anti-angiogenetic and antitumor activities. Nevertheless, the role and molecular mechanism underlying CLT-003 in pancreatic cancer remain to be elucidated.

Methods: Cell proliferation and apoptosis were detected using CCK-8, real-time cell analysis (RTCA), EdU, and flow cytometric assays. Cellular mobility and invasive capacity were detected using wound-healing, Transwell, and cell motility assays. Tumor growth and metastasis were determined using the mouse subcutaneous and pancreatic cancer orthotopic liver metastasis models. The antitumor effects of CLT-003 were evaluated using patient-derived organoid (PDO) and patient-derived xenograft (PDX) models.

Results: CLT-003 significantly inhibited cellular proliferation, enhanced cellular apoptosis, and attenuated cellular invasion and migration of pancreatic cancer cells. Mechanistically, CLT-003 suppressed the translation of HIF-1α by inhibiting the PI3K/AKT/mTOR signaling pathway. In the mouse tumor models, CLT-003 significantly inhibited the growth and metastasis of pancreatic tumors. Moreover, the PDO and PDX models showed increased sensitivity to CLT-003 in pancreatic cancer with high HIF-1α expression compared to pancreatic cancer with low HIF-1α expression.

Conclusions: This study delineated the role and molecular mechanism of CLT-003 action in impeding the progression of pancreatic cancer and indicated its robust potential for the treatment of pancreatic cancer.

Objective: To describe temporal changes associated with deployment of an optical character recognition (OCR)-enabled One-Identity (One-ID) digital platform for rural cervical cancer screening, focusing on over-screening rates, CIN2+ detection, colposcopy follow-up, and CIN2+ management.

Methods: A multi-county pre-post observational study was conducted in six rural counties in Shanxi, Yunnan, and Sichuan Provinces (2021-2024), encompassing 153,978 encounters. The digital platform integrates OCR identity capture, deterministic One-ID linkage, and real-time duplicate alerts. Over-screening proportions before and after digital deployment were compared, changes in CIN2+ detection rate were evaluated, and colposcopy follow-up and CIN2+ management were assessed. Differences were tested with χ² or Fisher's exact tests.

Results: Among 153,978 encounters, the proportion of over-screening decreased from 12.64% in 2023 to 0.17% in 2024 with an absolute reduction of 12.17% (95% CI: 11.94-12.40; P < 0.001). The share of women receiving a first screening within the preceding 3 y increased from 78.3% to 88.2% (P < 0.001). Colposcopy completion improved from 64.1% to 84.9%. The CIN2+ detection rate rose from 0.35% (2021-2023 pooled) to 0.67% in 2024 (P < 0.001) and CIN2+ management completion increased from 56.0% to 76.2% (95% CI: 13.3-27.2; P < 0.001). These improvements were consistent across age groups, counties, and screening strategies.

Conclusions: The OCR-enabled One-ID platform substantially reduced over-screening, increased CIN2+ detection rate, and strengthened case follow-up/management, particularly where baseline tracking was weak, supporting scalable digital reinforcement of rural screening programmes.

Immunotherapy, particularly immune checkpoint inhibitors (ICIs) programmed death-ligand 1/programmed death-1 (PD-L1/PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), has heralded a new era of tumor treatment. Although ICIs have clinical benefits, their complex heterogeneity and diverse resistance mechanisms critically limit their efficacy. Neoantigens, arising from tumor-specific alterations, offer novel targets for individualized immunotherapy, because of their high immunogenicity and tumor specificity. In the past decade, neoantigen-based tumor vaccines have been demonstrated to be a promising immunotherapy strategy to prime the tumor-specific immune response. These therapeutic vaccines include peptide vaccines, nucleic acid vaccines, and dendritic cell (DC) vaccines, and are categorized according to the neoantigen source and delivery method. In vivo, neoantigens are processed and presented by antigen-presenting cells (APCs) via the peptide-Major Histocompatibility Complex (pMHC) for T cell recognition, thereby triggering specific immune responses. Because DCs, the most potent APCs, play crucial roles in antitumor immunity, neoantigen-based DC vaccines provide a promising therapeutic strategy. A series of global clinical trials are exploring the safety, feasibility, and efficacy of neoantigen-based DC vaccines in tumors. This review focuses on current progress in clinical research on neoantigen-based DC vaccines in the treatment of solid tumors.