Molecular Biomarker–Based Screening for Early Detection of Cervical Cancer

Patterson, Bruce K.; Domanik, Richard; Wernke, Paul; Gombrich, Matthew

doi:10.1159/000327185

Cited by 6 publications

(6 citation statements)

References 9 publications

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“…Cell proliferation antigens such as Ki-67 and proliferating cell nuclear antigen have been assessed for their ability to detect atypical cervical cells, 22 as have the cell cycle (DNA replication)-dependent antigens cdc2, cdc6, and Mcm5. 23,24 Because these are cell-cycle markers and commonly are present in nonneoplastic, regenerating cells, the use of these markers for cervical cancer screening is limited. The MN transmembrane glycoprotein antigen has been studied extensively, and, although the specificity of this marker was high, the sensitivity for abnormal cells was relatively low.…”

Section: Discussionmentioning

confidence: 99%

High-Throughput Cervical Cancer Screening Using Intracellular Human PapillomavirusE6andE7mRNA Quantification by Flow Cytometry

Narimatsu¹,

Patterson²

2005

Am J Clin Pathol

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The Papanicolaou (Pap) test, based solely on the morphologic examination of exfoliated cells from the cervix, has reduced deaths due to cervical cancer by 74% in the United States during the past 40 years. During that time, the molecular mechanisms of cervical cancer have largely been elucidated. Taken together, these observations have identified a need for a high-throughput cervical cancer screening assay. We report the development of a high-throughput assay consisting of simultaneous immunophenotyping and ultrasensitive in situ hybridization for human papillomavirus (HPV) E6 and E7 messenger RNA (mRNA). This assay can be performed in less than 3 hours directly from liquid-based cervical cytology specimens. Overall, HPV fluorescence in situ hybridization (FISH) for E6 and E7 mRNA demonstrated 83.3% sensitivity and 91.3% specificity for high-grade squamous intraepithelial lesions compared with the Pap test in 231 liquid-based cytology samples from 2 cohorts. In a subset of these samples, HPV FISH demonstrated higher sensitivity and specificity than Hybrid Capture (Digene, Gaithersburg, MD) for high-risk genotypes.

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Section: Discussionmentioning

confidence: 99%

High-Throughput Cervical Cancer Screening Using Intracellular Human PapillomavirusE6andE7mRNA Quantification by Flow Cytometry

Narimatsu¹,

Patterson²

2005

Am J Clin Pathol

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“…All four major cell populations were distinctly separated in all preservatives tested. Last, this method may also facilitate the use of immunophenotypic/molecular methods and flow cytometry for cervical cancer screening (14). For example, several methodologies are currently being used to identify the expression of certain human papillomavirus (HPV) genes and cellular proteins associated with cervical dysplasia and cervical cancer (14).…”

Section: Discussionmentioning

confidence: 99%

“…Last, this method may also facilitate the use of immunophenotypic/molecular methods and flow cytometry for cervical cancer screening (14). For example, several methodologies are currently being used to identify the expression of certain human papillomavirus (HPV) genes and cellular proteins associated with cervical dysplasia and cervical cancer (14). The popularity and increased utilization of liquid‐based cervical cytology is the ideal setting for future solution‐based assays that may augment or even replace slide‐based morphologic screening.…”

Section: Discussionmentioning

confidence: 99%

Determination of liquid‐based cervical cytology specimen adequacy using cellular light scatter and flow cytometry

Grundhoefer¹,

Patterson

2001

Cytometry

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“…The E7 protein is likely encoded by the E6*I or E6*II and for some time it was thought that this splicing event was a means of obtaining high levels of E7 expression. 20 In fact, a report by Stacey et al states that the HPV-16 E7 protein is also translated from full-length E6-E7 mRNA structures, demonstrating that splicing is not required for E7 synthesis. 21 Additionally, only the full length E6 protein, not the spliced E6 variants, is found to efficiently bind to and promote the degradation of p53 22 and it is further suggested that spliced transcripts of the HPV 18 E6 gene may encode an E6 modified protein that inhibits the full-length E6 mediated degradation of p53.…”

Section: Key Biological Properties Of the E6/e7 Mrna Technologymentioning

confidence: 99%

The potential of RNA as a target for national screening of pre-cancer

Karlsen

Muturi

Muyabwa

et al. 2018

J Public Health Afr

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Whole national screening of pre-cancer is done only in some few countries, dominated by The Netherlands, Denmark, UK, Norway and Finland. These national screenings are done combining national cancer registry, national public health and national medical bodies or hospitals. Until some few years ago national screening was only done using morphological or visual methods or technology. Today a number of molecular methods have been implemented to serve these national screening programs. Based on all the discussions within this review, it is clear that the main driving engine and the cause of cervical pre-cancer and the main cause of invasive cervical cancer is the expression of E6 and E7 oncoproteins from HPV 16, 18, 31, 33 and 45. However, the main challenge is the role of morphology or imaging-based diagnosis in the original definition of pre-cancer disease. This definition is not based on the cause of cervical precancer but based on a complex, subjective, morphological observations. The difference between these two definitions are discussed in this review. The unique discovery done while validating the first standardized detection technology used against mRNA, confirmed that the presence of both abnormal E6 and/or E7 mRNA and protein is the cause of cervical pre-cancer or severe neoplasia and the main cause of invasive cervical cancer. This confirmation was evident even though all these studies were disturbed by the above defined biases from morphology or imaging-based diagnosis. The use of the screening target that cause stable and high expression of the most carcinogenic compounds ever discovered, must cause a more accurate screening program. A number of studies have proved that the detection of E6/E7 mRNA followed-up by indirect or direct treatment in a well-organized national screening program, would reduce the incidence of cervical cancer. This review discusses the main studies involved in the scientific, clinical evaluation and how this unique technology could be used as a new medical gold standard for national screening of cervical pre-cancer.

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Molecular Biomarker–Based Screening for Early Detection of Cervical Cancer

Cited by 6 publications

References 9 publications

High-Throughput Cervical Cancer Screening Using Intracellular Human PapillomavirusE6andE7mRNA Quantification by Flow Cytometry

High-Throughput Cervical Cancer Screening Using Intracellular Human PapillomavirusE6andE7mRNA Quantification by Flow Cytometry

Determination of liquid‐based cervical cytology specimen adequacy using cellular light scatter and flow cytometry

The potential of RNA as a target for national screening of pre-cancer

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