Patterns of Co-infection of HPV52 With Other HPV Genotypes and Their Risks of Cervical Precancer and Carcinoma

Abstract

Human papillomavirus 52 (HPV52) is the second most frequent HPV type in high-grade squamous intraepithelial lesion (HSIL) cases in China. However, few researchers have explored the co-infection of HPV52 with other HPV genotypes and their correlation with cervical lesions. In this study, 13,809 HPV52-positive patients visiting the Obstetrics and Gynecology Hospital of Fudan University from 2018 to 2023 were included in the first stage to investigate the risk of cervical lesions among different multiple infection patterns. Another 443 HPV52-positive patients were further included for sequence alignment and phylogenetic analysis. In the current study, the most common HPV52 dual-infection patterns were as follows: HPV16 + HPV52, HPV52 + HPV58, HPV52 + HPV53, and HPV52 + HPV81. Compared with HPV52 single infection, the risk of HSIL+ was increased in HPV16 + HPV52 (OR = 3.47, 95% CI: 2.56, 4.69) and HPV52 + HPV58 (OR = 1.99, 95% CI: 1.35, 2.92) groups. The most common triple-infection patterns were HPV16 + HPV52 + HPV53 and HPV52 + HPV53 + HPV81, followed by HPV52 + HPV53 + HPV58. HPV53 was the most common co-infection type with HPV52 in cases of triple or more multiple infections. However, compared with dual infection, the addition of HPV53 did not affect the risk of HSIL+. Two synonymous mutations, G207A (p = 0.029) and C1203T (p = 0.021), showed statistically significant differences in distribution between single and multiple infection groups. Our results demonstrated that HPV52 showed preferences for co-infection with HPV16, 585,381. HPV52 co-infection with HPV16 and HPV58 increased the risk of HSIL+, while co-infection with HPV53 did not increase the risk of HSIL+. Virus variants with certain mutations may be more susceptible to multiple infections.

Keywords: HPV52; L1 variants; cervical squamous intraepithelial lesions; multiple infections.

Figure 1

Patterns of HPV52 co‐infection with other HPVs. The columns on the diagonal represented genotypes involved in dual infection, and the columns in the regions beyond the diagonal represented genotypes involved in triple infection. The green and red columns were the most frequent patterns of HPV52‐positive. Other infection patterns were shown in purple and blue.

Figure 2

Trends of the proportion of HPV16, 585 381 in HPV52 multiple infection.

Figure 3

Phylogenetic trees of HPV52 L1 genes from single (A) and multiple infection groups (B). Neighbor‐joining phylogenetic tree was constructed in MEGA software (version 11.0) using the Kimura 2‐parameter model. The number of bootstrap replications was set at 1000. The reference sequences were marked with solid dots.

Figure 4

Genetic variability of HPV52 L1 nucleotide sequences. Numbering refers to the sequence of the HPV52 lineage B2 prototype reference sequence (GenBank: HQ537743). Each row indicates the isolate identification and the nucleotide sequence alignment compared with the reference.