Evidence map›Paper›PMID 41358616›Full record

ArticleJournal of medical virology2025

High-Throughput Targeted Sequencing Identifies an HPV Methylation Panel for Detecting Cervical Lesion Progression.

Hui Liu, Jie Zhou, Yunxia Xiao, Yuming Zheng, Liyao Yu, Dirong Dong, Yanqing Shen, Wen Zhang, Wei Guo, Rui Tian and 5 more

Abstract read
In one paragraph

Article in Journal of medical virology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Observational
  2. Review
  3. Review
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Hui LiuDepartment of Pathology, Xi'an People's Hospital (Xi'an Fourth Hospital), Affiliated People's Hospital Northwest University, Xi'an, Shaanxi, China.
Jie ZhouDepartment of Gynecology, Yue Bei People's Hospital, Guangdong, Shaoguan, China.
Yunxia XiaoDepartment of Gynecologic Oncology, Women and Children's Hospital Affiliated to Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
Yuming ZhengHealth Management Center, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Liyao YuDepartment of Obstetrics and Gynecology, Academician expert workstation, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Dirong DongDepartment of Gynecologic Oncology, Women and Children's Hospital Affiliated to Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
Yanqing ShenDepartment of Obstetrics and Gynecology, Academician expert workstation, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Wen ZhangDepartment of Obstetrics and Gynecology, Academician expert workstation, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Wei GuoDepartment of Obstetrics and Gynecology, Academician expert workstation, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Rui TianGenerulor Co. Ltd., Zhuhai, Guangdong, China.
Xun TianDepartment of Obstetrics and Gynecology, Academician expert workstation, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Xia HuangDepartment of Obstetrics and Gynecology, Zhongxiang People's Hospital, Zhongxiang, Hubei, China.
Zheng HuDepartment of Gynecologic Oncology, Women and Children's Hospital Affiliated to Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
Lili SunDepartment of Gynecologic Oncology, Women and Children's Hospital Affiliated to Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
Chen CaoDepartment of Obstetrics and Gynecology, Academician expert workstation, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Funding

This study was supported by Noncommunicable Chronic Diseases-National Science and Technology Major Project (2025ZD0544102), Xi'an People's Hospital (Xi'an Fourth Hospital) Research Incubation Fund (LH-15), the National Natural Science Foundation of China (32171465, 82102392), the General Program of Natural Science Foundation of Guangdong Province of China (2021A1515012438), Guangdong Basic and Applied Basic Research Foundation (2020A1515110170), the National Ten Thousand Plan-Young Top Talents of China (80000-41180002), Key Technology R&D Program of Hubei (2025BCB053), Natural Science Foundation of Wuhan (2024040801020369).
6 · The paper itself

Abstract

High-risk human papillomavirus (hrHPV) infection is the primary cause of cervical cancer. However, hrHPV testing lacks specificity in detecting neoplastic changes. This study explored the utility of quantitative methylated HPV DNA markers for precise detection of cervical lesions. Using hybridization capture-based bisulfite sequencing, we analyzed genome-wide HPV methylation patterns. The study included a training cohort of 60 cervical exfoliated cell samples and a validation cohort of 29 samples. Analysis of 112 CpG sites across the HPV genome revealed that genome-wide HPV16 methylation levels correlated with disease progression. Squamous cell carcinoma (SCC) showed 1.4-fold higher methylation levels compared to normal tissue (p = 0.0032). Progressive methylation increases in the E5-α and L2 genes were observed across the spectrum of cervical lesion severity, from normal tissue through high-grade squamous intraepithelial lesion (HSIL) to SCC. Intersection analysis of differentially methylated CpG sites between HSIL vs Normal and SCC vs Normal identified 16 consistently hypermethylated CpG sites in the E5-α, E7, L2, and L1 genes, distinguishing both HSIL and SCC from normal tissue. This pilot study identifies a five-CpG methylation panel (E5-α_3887, E5-α_3941, E7_701, L2_4441, and L2_5128) as promising triage biomarkers for HPV16-positive women, achieving high discriminatory performance (AUC = 0.919 in a validation cohort) for detecting cervical lesions. This genome-wide capture sequencing identified novel HPV16 methylation markers that distinguish cervical lesions from normal tissue, supporting the feasibility of HPV methylation-based triage for HPV-positive women in cervical cancer screening.

Indexed as

DNA MethylationHigh-Throughput Nucleotide SequencingHuman papillomavirus 16PapillomaviridaePapillomavirus InfectionsUterine Cervical NeoplasmsAdultAgedCarcinoma, Squamous CellCpG IslandsDisease ProgressionDNA, ViralFemaleHumansMiddle AgedPilot ProjectsDNA, Viralcervical cancercervical intraepithelial neoplasiaHPV methylationhuman papillomavirus

Identifiers

PMID41358616
PMCPMC12683980

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.