Chen Zuyi, Cheng Qichen, Mu Xuejiao, Liu Youbin, Zhang Mingjing, Tian Di, Huang Yanlan, Bai Xia, Yang Yan, Li Qiongyao
Department of Laboratory Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
School of Laboratory Medicine, Zunyi Medical University, Zunyi, China.
J Med Virol. 2025 Jul;97(7):e70502. doi: 10.1002/jmv.70502.
Human papillomavirus type 58 (HPV58) poses a substantial burden in Asia; however, the interplay between its genetic variations, viral load, and clinical outcomes remains incompletely characterized. Therefore, we investigated HPV58 detection rates and E6/E7 allele frequency trends, and analyzed the positive selection, viral load, pathogenicity, and persistent infection capacity associated with specific genotypes/mutations using 239 743 exfoliated cervical cell samples. Our results show a gradual increase in HPV58 detection rates over time. Allele replacement occurs slowly, with significant changes manifesting after long-term accumulation. The E6 A388C(K93N) + E7 prototype enhanced short-term persistent infection capacity without increasing high-grade lesion pathogenicity, and its frequency increased. Conversely, E7 C632T (T20I) and G760A (G63S) mutations enhanced high-grade lesion pathogenicity, whereas G761A (G63D) reduced pathogenicity. HPV58 improves adaptive ability by increasing the persistent infection capacity without increasing the risk of high-grade lesions. High viral load was positively correlated with both pathogenicity and persistent infection capacity, suggesting its potential as a risk factor for predicting disease progression in HPV58 screening. No correlation was observed between HPV58 viral load and specific gene mutations/genotypes, indicating that alternative mechanisms likely drive allele replacement. This study provides insights to optimize HPV58 screening strategies and deepen understanding of its evolutionary dynamics.
人乳头瘤病毒58型（HPV58）在亚洲造成了相当大的负担；然而，其基因变异、病毒载量和临床结果之间的相互作用仍未完全明确。因此，我们使用239743份宫颈脱落细胞样本，调查了HPV58的检出率和E6/E7等位基因频率趋势，并分析了与特定基因型/突变相关的正选择、病毒载量、致病性和持续感染能力。我们的结果显示，HPV58的检出率随时间逐渐上升。等位基因替换发生缓慢，长期积累后才会出现显著变化。E6 A388C（K93N）+E7原型增强了短期持续感染能力，而不增加高级别病变的致病性，其频率增加。相反，E7 C632T（T20I）和G760A（G63S）突变增强了高级别病变的致病性，而G761A（G63D）降低了致病性。HPV58通过增加持续感染能力而不增加高级别病变风险来提高适应能力。高病毒载量与致病性和持续感染能力均呈正相关，表明其在HPV58筛查中作为预测疾病进展风险因素的潜力。未观察到HPV58病毒载量与特定基因突变/基因型之间的相关性，这表明可能存在其他机制驱动等位基因替换。本研究为优化HPV58筛查策略和加深对其进化动力学的理解提供了见解。
