Detection Rate, Genetic Polymorphism, Viral Load, Persistent Infection Capacity, and Pathogenicity of Human...

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.