To summarize the distribution of types of human papillomavirus (HPV) associated with HPV-related diseases and investigate the potential causes of high prevalence of HPV 52 and 58 by summarizing the prevalence of lineages, sub-lineages, and mutations among Chinese women. We searched PubMed, EMBASE, CNKI, and WanFang from January, 2012 to June, 2023 to identify all the eligible studies. We excluded patients who had received HPV vaccinations. Data were summarized in tables and cloud/rain maps. A total of 102 studies reporting HPV distribution and 15 studies reporting HPV52/HPV58 variants were extracted. Among Chinese women, the top five prevalent HPV types associated with cervical cancer (CC) were HPV16, 18, 58, 52, and 33. In patients with vaginal cancers and precancerous lesions, the most common HPV types were 16 and 52 followed by 58. For women with condyloma acuminatum (CA), the most common HPV types were 11 and 6. In Chinese women with HPV infection, lineage B was the most prominently identified for HPV52, and lineage A was the most common for HPV58. In addition to HPV types 16, which is prevalent worldwide, our findings revealed the unique high prevalence of HPV 52/58 among Chinese women with HPV-related diseases. HPV 52 variants were predominantly biased toward lineage B and sub-lineage B2, and HPV 58 variants were strongly biased toward lineage A and sub-lineage A1. Further investigations on the association between the high prevalent lineage and sub-lineage in HPV 52/58 and the risk of cancer risk are needed. Our findings underscore the importance of vaccination with the nine-valent HPV vaccine in China.

Human papillomavirus is a predominant sexually transmitted viral pathogen. Our objective was to analyze the relative distribution of genotypes over time and to determine the genotypes associated with adverse clinical lesions. The study was based on data from adult women with cytological abnormalities from whom histological samples were obtained from 2005 to 2021. HPV genotyping was performed using PCR and INNO-LiPA assay (Fujirebio). Among the 1,017 HPV-positive biopsies, 732 (72%) were infected with a single HPV genotype and 285 (28%) were infected with several HPV genotypes. Most of the infections involved the high-risk genotypes 16, 31, and 52. Throughout the study period, HPV 16 was the most encountered genotype (541, 53.2%), while HPV 18 was rather under-represented (46, 4.5%), especially in invasive cervical carcinoma. HVP52 (165, 16.2%) was detected mainly from 2008 to 2014, and its distribution reached 19.7% in 2011. Such epidemiological data underlines the possibility of an emergence of a high-risk genotype. The most detected low-risk HPV in combination with high-risk HPV was HPV 54 in 6.5% of samples. Monoinfection by HPV 16 led statistically more often to severe lesions than multi-infection involving HPV 16 (p < 0.001), while for HPV 52, 31 or 33, multi-infections were significantly associated with severe lesions (p < 0.001 for each of these three genotypes). HPV 16 was involved in 55.2% of high-grade lesions and in situ carcinoma and 76.3% of invasive carcinomas. In severe lesions, HPV 16 participation was predominant, whereas diverse genotypes were seen in low-grade lesions. Importantly, we observed that high-risk genotypes, for example HPV 52, can emerge for a few years then decrease even without vaccine pressure.

The goal of this study was to identify human papillomavirus (HPV) type 52 genetic and epigenetic changes associated with high-grade cervical precancer and cancer. Patients were selected from the HPV Persistence and Progression (PaP) cohort, a cervical cancer screening program at Kaiser Permanente Northern California (KPNC). We performed a nested case-control study of 89 HPV52-positive women, including 50 cases with predominantly cervical intraepithelial neoplasia grade 3 (CIN3) and 39 controls without evidence of abnormalities. We conducted methylation analyses using Illumina sequencing and viral whole genome Sanger sequencing. Of the 24 CpG sites examined, increased methylation at CpG site 5615 in HPV52 L1 region was the most significantly associated with CIN3, with a difference in median methylation of 17.9% (odds ratio (OR) = 4.8, 95% confidence interval (CI) = 1.9-11.8) and an area under the curve of 0.73 (AUC; 95% CI = 0.62-0.83). Complete genomic sequencing of HPV52 isolates revealed associations between SNPs present in sublineage C2 and a higher risk of CIN3, with ORs ranging from 2.8 to 3.3. This study identified genetic and epigenetic HPV52 variants associated with high risk for cervical precancer, improving the potential for early diagnosis of cervical neoplasia caused by HPV52.