Siewchaisakul Pallop, Fann Jean Ching-Yuan, Chen Meng-Kan, Hsu Chen-Yang
Faculty of Public Health, Chiang Mai University, Chiang Mai 50200, Thailand.
Department of Health Services Administration, College of Public Health, China Medical University, Taichung 406040, Taiwan.
Int J Mol Sci. 2025 Jun 23;26(13):6016. doi: 10.3390/ijms26136016.
Precision prevention strategies for cervical cancer that integrate genetic biomarkers provide opportunities for personalized risk assessment and optimized preventive measures. An HPV infection-Precancerous-Cancer risk assessment model incorporating genetic polymorphisms and DNA methylation was developed to better understand the regression and progression of cervical lesions by HPV infection status. Utilizing a virtual cohort of 300,000 Taiwanese women aged 30 years and older, our model simulated the natural history of cervical cancer, capturing transitions from a healthy state through precancerous lesions (LSILs and HSILs) to invasive carcinoma and incorporating the possibility of regression between states. Genetic and epigenetic markers significantly influenced disease transitions, demonstrating heterogeneous risks among women with distinct molecular biomarker profiles. Guided by these individual risk profiles, tailored preventive strategies including varying intervals for Pap smear screening, HPV DNA testing, and HPV vaccination showed improved efficiency and effectiveness in reducing cervical cancer incidence compared to uniform approaches. The proposed dynamic transition model of cervical neoplasms incorporating genetic biomarkers can facilitate the development of an individualized risk-based approach for guiding precision prevention towards the goal of cervical cancer elimination.
整合基因生物标志物的宫颈癌精准预防策略为个性化风险评估和优化预防措施提供了机会。开发了一种结合基因多态性和DNA甲基化的HPV感染-癌前病变-癌症风险评估模型，以更好地了解HPV感染状态下宫颈病变的消退和进展情况。利用一个由30万名30岁及以上台湾女性组成的虚拟队列，我们的模型模拟了宫颈癌的自然史，捕捉了从健康状态到癌前病变（低级别鳞状上皮内病变和高级别鳞状上皮内病变）再到浸润性癌的转变，并纳入了不同状态之间消退的可能性。基因和表观遗传标记显著影响疾病转变，表明具有不同分子生物标志物特征的女性存在异质性风险。在这些个体风险特征的指导下，与统一方法相比，包括调整巴氏涂片筛查、HPV DNA检测和HPV疫苗接种间隔的定制预防策略在降低宫颈癌发病率方面显示出更高的效率和效果。所提出的纳入基因生物标志物的宫颈肿瘤动态转变模型有助于制定基于个体风险的方法，以指导精准预防，实现消除宫颈癌的目标。
