Presence of High-Risk HPV mRNA in Relation to Future High-Grade Lesions among High-Risk HPV DNA Positive Women with Minor Cytological Abnormalities

Johansson, Hanna Katarina Lilith; Bjelkenkrantz, Kaj; Darlin, Lotten; Dilllner, Joakim; Forslund, Ola

doi:10.1371/journal.pone.0124460

Cited by 31 publications

(32 citation statements)

References 26 publications

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“…Those data are comparable to the results of other studies reporting clearance rates of about 40% in older women within an average time span of four months (4,10,19). The data of recent studies indicate that the long-term protective effect of a negative HPV mRNA result is comparable to that of negative HPV-DNA test (15,20,21).…”

Section: Discussionsupporting

confidence: 86%

“…HPV analyses in this age group offering a higher sensitivity. (15). Like in our study, all women who were diagnosed with CIN 3 or worse were HPV mRNA positive at baseline.…”

Section: Discussionsupporting

confidence: 62%

“…In all cases the following LBC results were classified as benign and cervical biopsy could confirm the presence of normal underlying tissue conditions. Furthermore the results of a long-term follow-up study could demonstrate that a negative APTIMA cotesting result among HPV-DNA positive women with minor cytological abnormalities at baseline was associated with a high negative predictive value of 100% for CIN 3 or worse within the following four years (15). Even though it seems that HPV mRNA negative women with cytological ASCUS or LSIL might be re-screened safely at four year intervals, further long-term studies are necessary to evaluate if these assumptions can also be applied to the postmenopausal patient cohort.…”

Section: Discussionmentioning

confidence: 99%

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Increased risk for development of severe cervical dysplasia among postmenopausal women with normal cytology and presence of HPV mRNA

Asciutto

Borgfeldt

Forslund³

2020

Preprint

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Background: During 2013 and 2016 the Region of Skåne, Sweden, started to analyse human papillomavirus (HPV) and cytology in postmenopausal women 60-65 years of age. Our aim was to evaluate if the presence of high-risk (HR) HPV mRNA could predict the development of cervical abnormalities among HR-HPV DNA positive women with normal cytology. Methods: A total of 271 women, 60-65 years of age, underwent liquid based cytology (LBC) and HPV testing by using the HR-HPV DNA MGP-PCR-Luminex assay. HR-HPV DNA-positive women with normal cytology underwent complimentary HPV mRNA testing (Aptima, Hologic). Over a period of 49 months (SD 11.0) the women received regular follow-up at intervals of 12-18 months. Women with abnormal cytology and/or a positive HR-HPV result at two subsequent visits were scheduled for colposcopy and clinical examination. Results: Over the surveillance period, 3.6% (10/271) of the HR-HPV DNA positive women developed histologically confirmed high-grade squamous intraepithelial lesions (HSILs) or worse and 13.3% (36/271) were diagnosed with cervical atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesions (LSILs). The cumulative incidence rates (CIR) were 29.7% (CI 24.8-30.1) for HSIL or worse among HPV mRNA-positive women at enrolment (39.4% 107/271) and 0% among HPV mRNA negative women (60.5%, 164/271), (p=0.002). The corresponding CIRs for ASCUS and LSIL was 59.9% (95% CI 59.3-66.2) and 26.1% (95 %CI 16.5-35.9), (p=0.001). Conclusions : Postmenopausal women with normal cytology along with presence of HR-HPV mRNA are at increased risk for development of severe cervical dysplasia, in contrast to those women with negative HR-HPV mRNA.

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Section: Discussionsupporting

confidence: 86%

“…HPV analyses in this age group offering a higher sensitivity. (15). Like in our study, all women who were diagnosed with CIN 3 or worse were HPV mRNA positive at baseline.…”

Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

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Increased risk for development of severe cervical dysplasia among postmenopausal women with normal cytology and presence of HPV mRNA

Asciutto

Borgfeldt

Forslund³

2020

Preprint

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“…Many discovery approaches to find HPV associated cervical cancer screening biomarkers are currently underway, of which the HR-HPV E6/E7 mRNA test is a promising non-invasive biomarker for the detection of high grade cervical lesion (CIN2+) enabling detection of the HPV infection and simultaneously predicting the change of cervical lesions [32][33][34][35][36][37][38][39][40]. This is because continuous expression of E6/E7 oncogenes of HR-HPVs is necessary for the development and maintenance of the dysplastic phenotype [41].…”

Section: Introductionmentioning

confidence: 99%

HPV E6/E7 mRNA test for the detection of high grade cervical intraepithelial neoplasia (CIN2+): a systematic review

Derbie

Mekonnen

Woldeamanuel

et al. 2020

Infect Agents Cancer

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Background: Genital infection with certain types of Human papillomavirus (HPV) is a major cause of cervical cancer globally. For early detection of premalignant dysplasia, evidences are coming out on the usefulness of HPV E6/E7 mRNA test as a potential tool compared with cytology and HPV DNA testing. Taking into account shortage of compiled data on this field, the aim of this systematic review was to describe the latest diagnostic performance of HPV E6/E7 mRNA testing to detect high grade cervical lesions (CIN2+) where by histology was taken as a gold standard. Methods: Articles published in English were systematically searched using key words from PubMed/Medline and SCOPUS. In addition, Google Scholar and the Google database were searched manually for grey literature. Two reviewers independently assessed study eligibility, risk of bias and extracted the data. We performed a descriptive presentation of the performance of E6/E7 mRNA test (in terms of sensitivity, specificity, negative and positive predictive values) for the detection of CIN2 +. Results: Out of 231 applicable citations, we have included 29 articles that included a total of 23,576 study participants (age range, 15-84 years) who had different cervical pathologies. Among the participants who had cervical histology, the proportion of CIN2+ was between 10.6 and 90.6%. Using histology as a gold standard, 11 studies evaluated the PreTect HPV Proofer, 7 studies evaluated the APTIMA HPV assay (Gen-Probe) and 6 studies evaluated the Quantivirus® HPV assay. The diagnostic performance of these three most common mRNA testing tools to detect CIN2+ was; 1) PreTect Proofer; median sensitivity 83%, specificity 73%, PPV 70 and NPV 88.9%. 2) APTIMA assay; median sensitivity 91.4%, specificity 46.2%, PPV 34.3% and NPV 96.3%. 3) Quantivirus®: median sensitivity 86.1%, specificity 54.6%, PPV 54.3% and NPV was at 89.3%. Further, the area under the receiver operating characteristics (AU-ROC) curve varied between 63.8 and 90.9%. Conclusions: The reported diagnostic accuracy implies that HPV mRNA based tests possess diagnostic relevance to detect CIN2+ and could potentially be considered in areas where there is no histology facility. Further studies including its cost should be considered.

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“…Epidemiological and clinical studies have established a causal association between persistent infection of high-risk human papilloma virus (HR-HPV) types (including HPV 16 and 18) and cervical carcinogenesis (3), with the contribution of additional cofactors including smoking or the use of oral contraceptives (4). It is known that the integration of HR-HPV DNA into the host cell genome results in elevated expression of HPV E6 and E7 oncoproteins (5), which subsequently allows the virus to replicate through inhibitory effects on the tumor suppressor proteins p53 and retinoblastoma protein, respectively (6,7). The inhibition of these tumor suppressors results in uncontrolled cellular proliferation and the accumulation of specific epigenetic changes in the host cell genome, driving progression to a malignant phenotype (3).…”

Section: Introductionmentioning

confidence: 99%

Investigation of differentially-expressed microRNAs and genes in cervical cancer using an integrated bioinformatics analysis

Zhou

Shi

et al. 2017

Oncology Letters

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Abstract. Cervical cancer is one of the most common types of cancer among women worldwide. In order to identify the microRNAs (miRNAs/miRs) and mRNAs associated with the carcinogenesis of cervical cancer, and to investigate the molecular mechanisms of cervical cancer, an miRNA microarray, GSE30656, and 3 mRNA microarrays, GSE63514, GSE39001 and GSE9750, for cervical cancer were retrieved from Gene Expression Omnibus. These datasets were analyzed in order to obtain differentially-expressed genes (DEGs) and miRNAs using the GEO2R tool. Gene Ontology (GO) and pathway enrichment analysis for DEGs were performed using the Database for Annotation, Visualization and Integrated Discovery. Protein-protein interaction (PPI) analysis for DEGs was conducted using The Search Tool for the Retrieval of Interacting Genes software and visualized using Cytoscape, followed by hub gene identification, and biological process and pathway enrichment analysis of the module selected from the PPI network using the Molecular Complex Detection plugin. In addition, miRecords was applied to predict the targets of differentially-expressed miRNAs. A total of 44 DEGs and 15 differentially-expressed miRNAs were identified. These DEGs were mainly enriched in GO terms associated with the cell cycle. In the PPI network, cyclin-dependent kinase 1, topoisomerase DNA IIα, aurora kinase A (AURKA) and minichromosome maintenance complex component 2 (MCM2) had higher degrees of connectivity. A significant module was detected from the PPI network. AURKA, MCM2 and kinesin family member 20A exhibited higher degrees in this module, while the genes in the module were mainly involved in the cell cycle and the DNA replication pathway. In addition, estrogen receptor 1 was predicted as the potential target of 13 miRNAs. A total of 10 DEGs were identified as potential targets of miR-203. In conclusion, the results indicated that microarray dataset analysis may provide a useful method for the identification of key genes and patterns to successfully identify determinants of the carcinogenesis of cervical cancer. The functional studies of candidate genes and miRNAs from these databases may lead to an increased understanding of the development of cervical cancer.

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Presence of High-Risk HPV mRNA in Relation to Future High-Grade Lesions among High-Risk HPV DNA Positive Women with Minor Cytological Abnormalities

Cited by 31 publications

References 26 publications

Increased risk for development of severe cervical dysplasia among postmenopausal women with normal cytology and presence of HPV mRNA

Increased risk for development of severe cervical dysplasia among postmenopausal women with normal cytology and presence of HPV mRNA

HPV E6/E7 mRNA test for the detection of high grade cervical intraepithelial neoplasia (CIN2+): a systematic review

Investigation of differentially-expressed microRNAs and genes in cervical cancer using an integrated bioinformatics analysis

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