Cancer Biology and Medicine

Identification of novel Lynch syndrome mutations in Chinese patients with endometriod endometrial cancer

Cervical cancer burden and trends in China, 2000–2020: Asia-Pacific international comparisons and insights for elimination goals

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.

Evaluation of the multiple HPV-based “screen and triage” algorithms in real-world settings of rural China

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.

Accelerating the elimination of global cervical cancer through intelligent training for colposcopy

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.

Evaluation of an intelligent digital platform for population management in cervical cancer screening

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.

Impact of government-organized screening programs on the economic burden of cervical cancer across five disease courses: a multistage regression and mediation analysis

Objective: To evaluate the impact of government-organized screening on the economic burden among patients with cervical cancer and precancerous lesions, and explore mediating pathways across diagnosis, initial treatment, radiotherapy/chemotherapy, follow-up, and recurrence/progression/metastasis. Methods: A multicentre, nationwide survey across 5 disease courses was conducted from 26 hospitals in China. Multivariable regression and structural equation modeling were used to assess the effects of government-organized screening on economic burden by comparing government-organized screening with workplace check-up, self-paid check-up, and symptom-based detection. Results: Workplace check-up, self-paid check-up, and symptom-based detection were associated with progressively higher costs across diagnosis [β: 1.10, 95% confidence interval (CI): 0.54–1.67; β: 1.46, 95% CI: 1.00–1.92; and β: 1.68, 95% CI: 1.25–2.11, respectively], initial treatment (β: 0.36, 95% CI: 0.18–0.55; β: 0.51, 95% CI: 0.35–0.66; and β: 0.56, 95% CI: 0.42–0.70, respectively), and follow-up (β: 0.63, 95% CI: 0.38–0.88; β: 0.83, 95% CI: 0.61–1.04; and β: 0.85, 95% CI: 0.65–1.06, respectively) compared to government-organized screening (all P < 0.05). Earlier clinical staging and greater use of lower-level hospitals mediated 44.74%–54.97% of cost differences in diagnosis, 73.27%–85.04% in initial treatment, and 30.38%–54.73% in follow-up. Fifteen percent of the cost differences during initial treatment were related to lower overtreatment for precancerous lesions. Conclusions: Government-led cervical cancer screening was associated with lower economic burden with pathways involving earlier-stage diagnosis, reduced overtreatment, and decreased reliance on higher-level hospitals, suggesting potential clinical benefits, efficient resource use, and improved equity in cancer care.

Artificial intelligence strengthenes cervical cancer screening – present and future

Cervical cancer is a severe threat to women’s health. The majority of cervical cancer cases occur in developing countries. The WHO has proposed screening 70% of women with high-performance tests between 35 and 45 years of age by 2030 to accelerate the elimination of cervical cancer. Due to an inadequate health infrastructure and organized screening strategy, most low- and middle-income countries are still far from achieving this goal. As part of the efforts to increase performance of cervical cancer screening, it is necessary to investigate the most accurate, efficient, and effective methods and strategies. Artificial intelligence (AI) is rapidly expanding its application in cancer screening and diagnosis and deep learning algorithms have offered human-like interpretation capabilities on various medical images. AI will soon have a more significant role in improving the implementation of cervical cancer screening, management, and follow-up. This review aims to report the state of AI with respect to cervical cancer screening. We discuss the primary AI applications and development of AI technology for image recognition applied to detection of abnormal cytology and cervical neoplastic diseases, as well as the challenges that we anticipate in the future.

Targeting endoplasmic reticulum stress signaling in ovarian cancer therapy

The endoplasmic reticulum (ER), an organelle present in various eukaryotic cells, is responsible for intracellular protein synthesis, post-translational modification, and folding and transport, as well as the regulation of lipid and steroid metabolism and Ca2+ homeostasis. Hypoxia, nutrient deficiency, and a low pH tumor microenvironment lead to the accumulation of misfolded or unfolded proteins in the ER, thus activating ER stress (ERS) and the unfolded protein response, and resulting in either restoration of cellular homeostasis or cell death. ERS plays a crucial role in cancer oncogenesis, progression, and response to therapies. This article reviews current studies relating ERS to ovarian cancer, the most lethal gynecologic malignancy among women globally, and discusses pharmacological agents and possible targets for therapeutic intervention.

Cancer risk in relatives of BRCA1/2 pathogenic variant carriers in a large series of unselected patients with breast cancer

Objective: The spectrum and risk of cancer in relatives of BRCA1/2 pathogenic variant carriers in the Chinese population have not been established. Methods: A family history of cancer in 9903 unselected breast cancer patients was retrospectively analyzed. BRCA1/2 status was determined for all patients and relative risks (RRs) were calculated to evaluate cancer risk in relatives of the patients. Results: The incidences of breast cancer in female relatives of BRCA1 carriers, BRCA2 carriers, and non-carriers were 33.0%, 32.2%, and 7.7%, respectively. The corresponding incidences of ovarian cancer were 11.5%, 2.4%, and 0.5%, respectively. The incidences of pancreatic cancer in male relatives of BRCA1 carriers, BRCA2 carriers, and non-carriers were 1.4%, 2.7%, and 0.6%, respectively. The corresponding incidences of prostate cancer were 1.0%, 2.1%, and 0.4%, respectively. The risks of breast and ovarian cancers in female relatives of BRCA1 and BRCA2 carriers were significantly higher than female relatives of non-carriers (BRCA1: RR = 4.29, P < 0.001 and RR = 21.95, P < 0.001; BRCA2: RR = 4.19, P < 0.001 and RR = 4.65, P < 0.001, respectively). Additionally, higher risks of pancreatic and prostate cancers were noted in male relatives of BRCA2 carriers than non-carriers (RR = 4.34, P = 0.001 and RR = 4.86, P = 0.001, respectively). Conclusions: Female relatives of BRCA1 and BRCA2 carriers are at increased risk for breast and ovarian cancers, and male relatives of BRCA2 carriers are at increased risk for pancreatic and prostate cancers.

Cervical cancer prevention in China: where are we now, and what’s next?

The role of a drug-loaded poly (lactic co-glycolic acid) (PLGA) copolymer stent in the treatment of ovarian cancer

Biological and clinical aspects of HPV-related cancers

Cancer-related diseases represent the second overall cause of death worldwide. Human papilloma virus (HPV) is an infectious agent which is mainly sexually transmitted and may lead to HPV-associated cancers in both men and women. Almost all cervical cancers are HPV-associated, however, an increasing number of head and neck cancers (HNCs), especially oropharyngeal cancer, can be linked to HPV infection. Moreover, anogenital cancers, including vaginal, vulvar, penial, and anal cancers, represent a subset of HPV-related cancers. Whereas testing and prevention of cervical cancer have significantly improved over past decades, anogenital cancers remain more difficult to confirm. Current clinical trials including patients with HPV-related cancers focus on finding proper testing for all HPV-associated cancers as well as improve the currently applied treatments. The HPV viral oncoproteins, E6 and E7, lead to degradation of, respectively, p53 and pRb resulting in entering the S phase without G1 arrest. These high-risk HPV viral oncogenes alter numerous cellular processes, including DNA repair, angiogenesis, and/or apoptosis, which eventually result in carcinogenesis. Additionally, a comprehensive analysis of gene expression and alteration among a panel of DNA double strand breaks (DSB) repair genes in HPV-negative and HPV-positive HNC cancers reveals differences pointing to HPV-dependent modifications of DNA repair processes in these cancers. In this review, we discuss the current knowledge regarding HPV-related cancers, current screening, and treatment options as well as DNA damage response-related biological aspects of the HPV infection and clinical trials.

A therapeutic multi-epitope protein vaccine targeting HPV16 E6 E7 elicits potent tumor regression and cytotoxic immune responses

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.

Advances in ATM, ATR, WEE1, and CHK1/2 inhibitors in the treatment of PARP inhibitor-resistant ovarian cancer