Evidence map›Paper›PMID 27651839›Full record

ArticleClinical epigenetics2016

Molecular Pap smear: HPV genotype and DNA methylation of ADCY8, CDH8, and ZNF582 as an integrated biomarker for high-grade cervical cytology.

Jane Shen-Gunther, Chiou-Miin Wang, Graham M Poage, Chun-Lin Lin, Luis Perez, Nancy A Banks, Tim Hui-Ming Huang

Open access · goldAbstract read
In one paragraph

Article in Clinical epigenetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 8% of its field
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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.

  1. Pooled it
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  17. A survey of transcriptome complexity in Sus scrofa using single-molecule long-read sequencing.DNA research : an international journal for rapid publication of reports on genes and genomes · 2018
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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

7 authors at 2 institutions in 1 country.

Jane Shen-GuntherGynecologic Oncology & Clinical Investigation, Department of Clinical Investigation, Brooke Army Medical Center, 3698 Chambers Pass, Fort Sam Houston, TX 78234-6315 USA.ORCID 0000-0002-0876-9338
Chiou-Miin WangDepartment of Molecular Medicine, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229 USA.
Graham M PoageDepartment of Clinical Investigation, Brooke Army Medical Center, Fort Sam Houston, TX 78234 USA.
Chun-Lin LinDepartment of Molecular Medicine, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229 USA.
Luis PerezDepartment of Clinical Investigation, Brooke Army Medical Center, Fort Sam Houston, TX 78234 USA.
Nancy A BanksDepartment of Pathology and Area Laboratories, Brooke Army Medical Center, Fort Sam Houston, TX 78234 USA.
Tim Hui-Ming HuangDepartment of Molecular Medicine, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229 USA.
Brooke Army Medical Center · USThe University of Texas Health Science Center at San Antonio · US

Funding

Institute for Integration of Medicine & Science: A Partnership to Improve HealthUL1TR001120 · NCATS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI CLARK, ROBERT A, HARGREAVES, KENNETH M · 2013 to 2017
$16.5M
NCATS NIH HHS UL1 TR001120
6 · The paper itself

Abstract

backgroundThe Pap smear has remained the foundation for cervical cancer screening for over 70 years. With advancements in molecular diagnostics, primary high-risk human papillomavirus (hrHPV) screening has recently become an accepted stand-alone or co-test with conventional cytology. However, both diagnostic tests have distinct limitations. The aim of this study was to determine the association between HPV genotypes and cellular epigenetic modifications in three grades of cervical cytology for screening biomarker discovery.

methodsThis prospective, cross-sectional study used residual liquid-based cytology samples for HPV genotyping and epigenetic analysis. Extracted DNA was subjected to parallel polymerase chain reactions using three primer sets (MY09/11, FAP59/64, E6-E7 F/B) for HPV DNA amplification. HPV+ samples were genotyped by DNA sequencing. Promoter methylation of four candidate tumor suppressor genes (adenylate cyclase 8 (ADCY8), cadherin 8, type 2 (CDH8), MGMT, and zinc finger protein 582 (ZNF582)) out of 48 genes screened was quantified by bisulfite-pyrosequencing of genomic DNA. Independent validation of methylation profiles was performed by analyzing data from cervical cancer cell lines and clinical samples from The Cancer Genome Atlas (TCGA).

resultsTwo hundred seventy-seven quality cytology samples were analyzed. HPV was detected in 31/100 (31 %) negative for intraepithelial lesion or malignancy (NILM), 95/100 (95 %) low-grade squamous intraepithelial lesion (LSIL), and 71/77 (92 %) high-grade squamous intraepithelial lesion (HSIL) samples. The proportion of IARC-defined carcinogenic HPV types in sequenced samples correlated with worsening grade: NILM 7/29 (24 %), LSIL 53/92 (58 %), and HSIL 65/70 (93 %). Promoter methylation of ADCY8, CDH8, and ZNF582 was measured in 170 samples: NILM (N = 33), LSIL (N = 70), and HSIL (N = 67) also correlated with worsening grade. Similar hypermethylation patterns were found in cancer cell lines and TCGA samples. The combination of four biomarkers, i.e., HPV genotype and three-gene promoter methylation, predicted HSIL (AUC 0.89) better than HPV alone (AUC 0.74) by logistic regression and probabilistic modeling.

conclusionsHPV genotype and DNA methylation of ADCY8, CDH8, and ZNF582 are correlated with cytological grade. Collectively, these biomarkers may serve as a molecular classifier of Pap smears.

Indexed as

DNA MethylationAdenylyl CyclasesAdultCadherinsCell Line, TumorCross-Sectional StudiesDNA, ViralEarly Detection of CancerFemaleGenotypeHumansKruppel-Like Transcription FactorsMiddle AgedNeoplasm GradingPapanicolaou TestPapillomaviridaeadenylyl cyclase 8Adenylyl CyclasesCadherinsCDH8 protein, humanDNA, ViralKruppel-Like Transcription FactorsZNF582 protein, humanDNA methylationHPVHPV genotypingMolecular biomarkersMolecular diagnosticsPap smearPyrosequencing

Identifiers

PMID27651839
PMCPMC5022163
OpenAlexW2520386988

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.