Evidence map›Paper›PMID 42174462›Full record

ArticleBMC cancer2026

Identification and validation of CNTNAP2/PAX1 hypermethylation as an epigenetic biomarker panel for detection of cervical cancer and precancerous lesions in hrHPV-positive women.

Yuying He, Haiyan Yang, Chuang Zhang, Ruiwei Jiang, Kai Kang, Yuxue Wang, Dixian Luo, Dan Xiong

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Article in BMC cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Yuying HeShantou University Medical College, Shantou, Guangdong, 515041, China.
Haiyan YangShantou University Medical College, Shantou, Guangdong, 515041, China.
Chuang ZhangMedical Laboratory of Shenzhen Luohu People's Hospital, Shenzhen, Guangdong, 518000, China.
Ruiwei JiangMedical Laboratory of Shenzhen Luohu People's Hospital, Shenzhen, Guangdong, 518000, China.
Kai KangWomen and Children's Health Care Hospital of Luohu, Shenzhen, Guangdong, 518000, China.
Yuxue WangShantou University Medical College, Shantou, Guangdong, 515041, China.
Dixian LuoMedical Laboratory of Shenzhen Luohu People's Hospital, Shenzhen, Guangdong, 518000, China.
Dan XiongShantou University Medical College, Shantou, Guangdong, 515041, China. sunny543@126.com.

Funding

Guangdong Provincial Clinical Research Center for Laboratory Medicine 2023B110008National Natural Science Foundation of China 81772921the International Collaborative Project of Shenzhen Science and Technology program GJHZ20220913144213025the Science and Technology Planning Project of Shenzhen Municipality JCYJ20240811001945001,JCYJ20230807142806014the Shenzhen Key Medical Discipline SZXK054
6 · The paper itself

Abstract

backgroundCervical cancer remains a significant global health burden, and effective triage strategies are urgently needed for high-risk human papillomavirus (hrHPV)-positive women in screening programs. This study aimed to identify and validate DNA methylation markers for detecting cervical precancerous lesions in hrHPV-positive women.

methodsReduced representation bisulfite sequencing (RRBS) was performed on a discovery cohort (n = 17) to screen for differentially methylated candidate genes. Quantitative methylation-specific PCR (qMSP) was used to evaluate the performance of selected markers in an independent cohort of 347 hrHPV-positive women stratified into training (n = 154) and validation (n = 193) sets. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) curves, sensitivity, specificity, and area under the curve (AUC).

resultsAmong the candidates identified, CNTNAP2 and PAX1 methylation levels increased progressively with cervical disease severity (both P < 0.0001). In the independent validation set, the combined CNTNAP2/PAX1 panel achieved an AUC of 0.904 (95% CI: 0.853-0.942) for CIN2 + detection and 0.932 (95% CI: 0.887-0.963) for CIN3 + detection. The panel yielded a sensitivity of 73.8% and specificity of 95.5% for CIN2+, and a sensitivity of 89.2% and specificity of 87.8% for CIN3+. In comparison, HPV16/18 genotyping showed sensitivities of 54.1% for CIN2 + and 56.8% for CIN3+, with specificities of 81.1% and 76.3%, respectively. Cytology (≥ ASCUS) had higher sensitivity (CIN2+: 93.1%; CIN3+: 91.2%) but substantially lower specificity (CIN2+: 16.9%; CIN3+: 14.9%); notably, cytology specificity in this cohort was likely underestimated due to verification bias. The CNTNAP2/PAX1 panel outperformed both comparator methods in overall diagnostic accuracy.

conclusionsThe CNTNAP2/PAX1 methylation panel demonstrates robust diagnostic performance for detecting cervical precancerous lesions in hrHPV-positive women, supporting its potential utility as an objective and effective triage tool in hrHPV-based cervical cancer screening.

Indexed as

Biomarkers, TumorDNA MethylationMembrane ProteinsNerve Tissue ProteinsPaired Box Transcription FactorsPapillomavirus InfectionsPrecancerous ConditionsUterine Cervical NeoplasmsAdultEpigenesis, GeneticFemaleHuman Papillomavirus VirusesHumansMiddle AgedROC CurveUterine Cervical DysplasiaBiomarkers, TumorCNTNAP2 protein, humanMembrane ProteinsNerve Tissue ProteinsPaired Box Transcription FactorsPAX1 transcription factorCervical cancerCNTNAP2DNA methylationHigh-risk human papillomavirusPAX1Reduced representation bisulfite sequencing

Identifiers

PMID42174462
PMCPMC13371192

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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.