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The present study aims to investigate the genotype distribution of Human papillomavirus (HPV) and variations of HPV18 and HPV58 infection among 6538 females in Luoyang city during 2019–2021. The overall positive rate of females with HPV infection was 12.34%, with 9.74% were infected with single HPV and 2.60% with multiple HPVs. The prevalent rate of high-risk HPV (HR-HPV) was 9.85% and the top five HR-HPV genotypes were HPV52 (1.94%), HPV16 (1.93%), HPV58 (1.48%), HPV51 (1.02%) and HPVV39 (0.99%). Two peaks of HPV infections rates were observed in females aged ≤ 20 and 61–65 years old. To characterize mutations, 39 HPV18 and 56 HPV58 L1, E6 and E7 genes were sequenced and submitted to GenBank. In the HPV18 E6-E7-L1 sequences, 38 nucleotides changes were observed with 10/38 were non-synonymous mutations (5 in E6 gene, 1 in E7 gene and 4 in L1 gene). In the HPV58 E6-E7-L1 sequences, 53 nucleotides changes were observed with 23/53 were non-synonymous mutations (3 in E6 gene, 5 in E7 gene and 15 in L1 gene). Phylogenetic analysis based on L1 gene showed that 92.3% (36/39) of HPV18 isolates fell into sublineage A1 and 7.7% (3/39) belonged to A5. For HPV58, 75.0% (42/56) isolates belonged to sublineage A1 and 25.0% (14/56) were sublineage A2. There was no association between amino mutation and cervical lesions. The present study provides basic information about the distribution, genotypes and variations of HPV among females population in Luoyang city, which would assist in the formulation of HPV screening and vaccination programs and preventive strategies for HPV-attributable cancer in this region. [ABSTRACT FROM AUTHOR]