Molecular triage on HPV-positive samples in a cervical screening setting

To improve human papilloma virus (HPV) screening, more effective triage methods for HPV-positive samples need development and validation. Cytology, the most common triage method today, is subjective and can only be applied to professionally collected samples. Methylation status has been shown to be...

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Vydáno v:PloS one Ročník 20; číslo 10; s. e0333539
Hlavní autoři: Larsson, Gabriella Lillsunde, Carlsson, Jessica, Helenius, Gisela, Bergengren, Lovisa
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Public Library of Science 13.10.2025
Public Library of Science (PLoS)
Témata:
Adult
Aged
Biopsy
Cancer
Cellular biology
Cervical cancer
Cervix
Complications and side effects
Cytokines
Cytology
Diagnosis
DNA Methylation
Early Detection of Cancer - methods
Female
Genes
Genotype
Genotype & phenotype
Genotyping
Health care
Human papillomavirus
Humans
Infections
Lesions
Medical screening
Methylation
MicroRNAs - genetics
Middle Aged
Molecular diagnostic techniques
Papillomaviridae - genetics
Papillomaviridae - isolation & purification
Papillomavirus infections
Papillomavirus Infections - diagnosis
Papillomavirus Infections - genetics
Papillomavirus Infections - virology
Retrospective Studies
Risk factors
Sensitivity and Specificity
Triage - methods
Uterine Cervical Dysplasia - diagnosis
Uterine Cervical Dysplasia - genetics
Uterine Cervical Dysplasia - pathology
Uterine Cervical Dysplasia - virology
Uterine Cervical Neoplasms - diagnosis
Uterine Cervical Neoplasms - genetics
Uterine Cervical Neoplasms - pathology
Uterine Cervical Neoplasms - virology
Sweden
United States > US
ISSN:1932-6203, 1932-6203
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Popis
Shrnutí:To improve human papilloma virus (HPV) screening, more effective triage methods for HPV-positive samples need development and validation. Cytology, the most common triage method today, is subjective and can only be applied to professionally collected samples. Methylation status has been shown to be informative, as genes are highly methylated in HPV-induced cervical dysplasia and cancer. This study aimed to assess whether triaging HPV-positive samples using molecular methods, such as methylation and genotyping for high-risk HPV types, could be as effective as cytology in cervical screening. A retrospective biobank study was conducted on HPV-positive samples collected in 2017-2018, analyzing FAM19A4/MiR-124-2 hypermethylation and HPV genotyping for types 16, 18, 31, 33, 45, 52, and/or 59, comparing these results to cytology triage for detecting histologically confirmed high-grade squamous intraepithelial lesions (HSIL) and cancer. Results from 1915 positive screening samples were analyzed, including 1052 follow-up biopsies with 402 HSIL or cancer cases. Genotyping showed slightly higher sensitivity than cytology but lower specificity, while methylation had higher specificity but much lower sensitivity. Cytology's positive predictive value (PPV) was 36%, with lower PPVs for the molecular methods. Combining molecular methods increased the PPV but significantly reduced sensitivity. Based on these findings with molecular methods reducing sensitivity, we do not recommend adopting the molecular triage methods evaluated in this study in the Swedish setting. The trade-off between sensitivity and specificity does not support a change from the current cytology-based triage approach.
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ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0333539