Cervical cancer represents a significant global health concern, stemming from persistent infections with high-risk types of human papillomavirus (HPV). The understanding of cervical cancer’s clinical correlates, risk factors, molecular mechanisms, stages, and associated genetic mutations is important for early detection and improved treatment strategies. Through integrated analysis of clinical and molecular datasets, this study aims to identify key factors that are overlapping and distinct across four cohorts of different races and regions. Here, datasets from four distinct cohorts of patients from Uganda (N = 212), the United States of America (USA) (N = 228), China (N = 106), and Venezuela (N = 858) were examined to comprehensively explore the relationships between cervical cancer stages, HPV types (clades), productive HPV integration, and malignant genetic mutations. Cohort-specific findings included the occurrence frequencies of cervical cancer stages and grades. The majority of patients from the USA and China were diagnosed with stages I and II, while those from Uganda were diagnosed with stages II and III, reflecting levels of awareness and the availability of HPV vaccines and screening services. Conversely, cervical cancer and its stages were positively correlated with HPV types (clades), HPV integration, and risk-factor habits across the cohorts. Our findings indicate that the more common squamous cervical cancer can be potentially due to productive HPV16 (clade 9) integration. At the molecular level, pathways related to HPV infection, cancer-related conditions, and viral carcinogenesis were among the most significant pathways associated with mutated genes in cervical cancer (across cohorts). These findings collectively corroborate the prominent role of HPV infection and integration leading to genetic mutation and hence to the development of cervical cancer and its stages across patients of distinct races and regions.
宫颈癌是全球范围内一项重大的公共卫生问题，其根源在于高危型人乳头瘤病毒（HPV）的持续感染。深入理解宫颈癌的临床相关性、风险因素、分子机制、分期及相关基因突变，对于早期检测和优化治疗策略至关重要。本研究通过对临床与分子数据集的整合分析，旨在识别不同种族和地区四个队列中重叠与差异的关键因素。本研究系统分析了来自乌干达（N = 212）、美国（N = 228）、中国（N = 106）和委内瑞拉（N = 858）四个不同患者队列的数据集，以全面探究宫颈癌分期、HPV型别（进化支）、有效HPV整合与恶性基因突变之间的关联。队列特异性发现包括宫颈癌分期与分级的分布频率：美国和中国的患者大多被诊断为I期和II期，而乌干达患者则多为II期和III期，这反映了各地区对HPV疫苗及筛查服务的认知水平和可及性差异。相反，在所有队列中，宫颈癌及其分期均与HPV型别（进化支）、HPV整合以及风险行为习惯呈正相关。我们的研究结果表明，较为常见的鳞状宫颈癌可能与有效的HPV16（进化支9）整合有关。在分子层面，与HPV感染、癌症相关状态及病毒致癌作用相关的通路，是宫颈癌突变基因（跨队列）中最显著的相关通路。这些发现共同印证了HPV感染与整合在导致基因突变，进而推动不同种族和地区患者宫颈癌发生及进展中的核心作用。
肿瘤(癌症)患者之家