Prevalence and genotype distribution of cervical human papillomaviruses infection across cytology: A nationwide, cross-sectional study of over 1 million Chinese women from 2020 to 2024

<h2>Abstract</h2><h3>Background</h3> The paradigm of cervical cancer screening is undergoing a significant global shift. Meanwhile, China has been advancing its national immunization strategy for human papillomaviruses (HPV). However, large-scale, real-world epidemiological studies that systematically characterize the distribution of HPV genotypes across various cervical cytological findings remain limited. This study aims to evaluate the prevalence and genotype distribution of HPV infection in China over the past five years and to assess the epidemiological patterns across different cervical cytology grades, which may inform the optimization of screening protocols and vaccination policies in the Chinese population. <h3>Methods</h3> De-identified data from 1,191,312 women aged 20-79 years undergoing routine co-testing for HPV genotypes and cervical cytology across 26 provinces in China from January 2020 to December 2024 were analyzed. Cervical exfoliated cell samples were collected and tested for 23 HPV genotypes using the same DNA test kit and liquid-based cytology test under the same procedure. HPV genotypes were classified based on cervical cancer risk: high-risk (HR-HPV) and low-risk (LR-HPV). Cervical cytology categories were classified as negative for intraepithelial lesion or malignancy (NILM), and atypical squamous cells of undetermined significance or worse (ASC-US+). Weighted prevalence of HPV infection was standardized by age group and province. The distribution of HPV genotypes was stratified by cytology grades. <h3>Results</h3> The overall weighted prevalence of any-type HPV infection was 17.0% (95% CI: 16.8-17.3%), with HR-HPV at 13.1% and LR-HPV at 6.0%. Regarding regional variations, women from the northeastern and northwestern regions exhibited the highest prevalence of any-type HPV infection and HR-HPV infection. The most prevalent HPV genotypes were HPV 52 (3.36%), HPV 16 (2.56%), and HPV 58 (2.46%). And the most common co-infection pairs were HPV 52–HPV 53, HPV 16–HPV 52, HPV 16–HPV 58. HPV infection prevalence increased significantly with cytological abnormality, from 11.4% in NILM to 73.0% in ASC-US+. HPV infection in the NILM group showed a bimodal age distribution, with prominent peaks observed in the 20-24 and 60-64 years. Notably, a U-shaped distribution was seen for HR-HPV in women with ASC-US+. The genotype distribution shifted from dominance by HPV 52 and 58 in the NILM group to HPV 16 in the ASC-US+ group. <h3>Conclusion</h3> This nationwide study indicates a considerable burden of HPV infection in China, distinguished by the prominent prevalence of genotypes HPV 52 and HPV 58 in addition to the globally dominant HPV 16. Dynamic changes in the prevalence and genotype distribution of HPV infection across cytology grades suggest the importance of genotype-specific risk stratification in cervical cancer prevention strategies. These findings provide evidence supporting the implementation of national HPV vaccination and cervical cancer screening programs in China. <h3>Funding</h3> This study was supported by the National Natural Science Foundation of China (grant number 82504421) and National High Level Hospital Clinical Research Funding (Scientific Research Seed Fund of Peking University First Hospital, grant number 2024SF47).