Detection Rate, Genetic Polymorphism, Viral Load, Persistent Infection Capacity, and Pathogenicity of Human Papillomavirus Type 58

ABSTRACT 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.