Methylation Levels of CADM1, MAL, and MIR124-2 in Cervical Scrapes for Triage of HIV-Infected, High-Risk HPV-Positive Women in Kenya

Vuyst, Hugo De; Franceschi, Silvia; Plummer, Martyn; Mugo, Nelly; Sakr, Samah R.; Meijer, Chris J.L.M.; Heideman, Daniëlle A.M.; Tenet, Vanessa; Snijders, Peter J.F.; Hesselink, Albertus T.; Chung, Michael H.

doi:10.1097/qai.0000000000000744

Cited by 38 publications

(51 citation statements)

References 34 publications

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“…De Strooper et al [56]; endpoint CIN2+, sensitivity = 64, specificity = 84; endpoint CIN3+, sensitivity = 64, specificity = 79. De Vuyst et al [50]; endpoint CIN2+, sensitivity = 95, specificity = 46; endpoint CIN3+, sensitivity = 95, specificity = 46. Verhoef et al [28]; endpoint CIN2+, sensitivity = 74, specificity = 81; endpoint CIN3+, sensitivity = 78, specificity = 78.…”

Section: Virtues and Limitations Of Dna Methylation Testingmentioning

confidence: 99%

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Virtues and Weaknesses of DNA Methylation as a Test for Cervical Cancer Prevention

Lörincz¹

2016

Acta Cytologica

100

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in cervical tissue, close to 20 have been reported in different studies, and approximately 10 have been repeatedly shown to have elevated methylation in cervical cancers and highgrade CIN (CIN2 and CIN3), most prominently CADM1, EPB41L3, FAM19A4, MAL, PAX1 and SOX1. Obtaining consistent performance data from the literature is quite difficult because most methylation studies used a variety of different assay methodologies and had incomplete and/or biased clinical specimen sets, varying assay thresholds and disparate target gene regions. There have been relatively few validation studies of DNA methylation biomarkers in large population-based screening studies, but an encouraging development more recently is the execution of well-designed studies to test the true performance of the markers in real-world settings. Methylation of HPV genes, especially HPV16, HPV18, HPV31, HPV33 and HPV45, in disease progression has been a major focus of research. Elevated methylation of the HPV16 L1 and L2 open reading frames, in particular, is associated with CIN2, CIN3 and invasive cancer. Essentially all cancers have high levels of methylation for human genes and for driver HPV types, which suggests that quantitative methylation tests may have utility in predicting CIN2 and CIN3 that are likely to progress. It is still early in the process of development of methylation biomarkers, but already they are showing strong promise as a universal and systematic approach to molecular triage, applicable to all Key WordsEpigenetics · DNA methylation · Cervical intraepithelial neoplasia · Cervical cancer · Human papillomavirus · Biomarkers · Triage · Diagnostics · Molecular signature · Classifier · Score Abstract Epigenetics is the study of heritable and non-heritable genetic coding that is additive to information contained within classical DNA base pair sequences. Differential methylation has a fundamental role in the development and outcome of malignancies, chronic and degenerative diseases and aging. DNA methylation can be measured accurately and easily via various molecular methods and has become a key technology for research and healthcare delivery, with immediate roles in the elucidation of disease natural history, diagnostics and drug discovery. This review focuses on cancers of the lower genital tract, for which the most epigenetic information exists. DNA methylation has been proposed as a triage for women infected with human papillomavirus (HPV) and may eventually directly complement or replace HPV screening as a one-step molecular diagnostic and prognostic test. Methylation of human genes is strongly associated with cervical intraepithelial neoplasia (CIN) and cancer. Of the more than 100 human methylation biomarker genes tested so far

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Section: Virtues and Limitations Of Dna Methylation Testingmentioning

confidence: 99%

“…Lagos et al [29]; endpoint CIN2+, sensitivity = 54%, specificity = 66%; endpoint CIN3+, sensitivity = 64%, specificity = 66%. DeVuyst et al [50]; endpoint CIN2+ or CIN3+, sensitivity = 40%, specificity = 76%. Lorincz et al [35]; endpoint CIN2+, sensitivity = 54%, specificity = 71%.…”

Section: Virtues and Limitations Of Dna Methylation Testingmentioning

confidence: 99%

Virtues and Weaknesses of DNA Methylation as a Test for Cervical Cancer Prevention

Lörincz¹

2016

Acta Cytologica

100

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“…However, this method could be unsuitable for predicting the progression of cervical diseases. Nevertheless, other methods including p16/Ki‐67immunocytochemistry, DNA methylation of CADM1 MAL and mir‐124, and DNA methylation of paired box gene 1, could be used for identifying high‐grade squamous intraepithelial lesions in women with anomalous Papanicolaou test results. Sorbye et al .…”

Section: Discussionmentioning

confidence: 99%

“…However, this method could be unsuitable for predicting the progression of cervical diseases. Nevertheless, other methods including p16/Ki-67immunocytochemistry, 15 DNA methylation of CADM1 MAL and mir-124, 16 and DNA methylation of paired box gene 1, 17 could be used for identifying high-grade squamous intraepithelial lesions in women with anomalous Papanicolaou test results. Sorbye et al 18 reported predictive values comparable to repeat cytology when using the E6/ E7 mRNA assay to triage patients with ASCUS; however, this study only included a small number of histology specimens.…”

Section: Discussionmentioning

confidence: 99%

Detection of cervical intraepithelial neoplasia with HPVE6/E7 mRNA among women with atypical squamous cells of unknown significance

Rong

Zhi

et al. 2017

Int J Gynecol Obstet

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“…In a study from Kenyan HIV-infected women, exfoliated cervical cells were used to measure methylation levels of the CADM1, MAL, and MIR124-2 genes using quantitative methylation-specific polymerase chain reaction (24). When markers were combined into a single test, the test showed promising sensitivity for HSIL when compared with cytology, VIA and HPV16/18 genotyping.…”

Section: Introductionmentioning

confidence: 99%

Human papillomavirus-associated anal and cervical cancers in HIV-infected individuals

Palefsky

2017

Current Opinion in HIV and AIDS

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Purpose of review The incidence of human papillomavirus (HPV)-related cancers has increased (anal cancer) or not declined (cervical cancer) since the introduction of antiretroviral therapy (ART). This article reviews recent data on incidence and prevention efforts for HPV-related cancers in the ART era. Recent findings ART may confer some benefit with respect to reducing the risk of anal HSIL and cancer, but the degree of that benefit appears to be limited. The prevalence of anal HPV infection, anal HSIL and anal cancer remain high among individuals on effective ART. The incidence of cervical cancer is high among HIV-infected women, particularly in countries where there are no organized cervical cancer prevention programs. Efforts are in progress to define optimal screen-and-treat cervical cancer prevention programs in different clinical settings and to define the efficacy of secondary prevention programs for prevention of anal cancer. Summary HPV-related cancers are likely to remain an important problem in HIV-infected men and women for the foreseeable future, even among those on effective ART.

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Methylation Levels of CADM1, MAL, and MIR124-2 in Cervical Scrapes for Triage of HIV-Infected, High-Risk HPV-Positive Women in Kenya

Abstract: Methylation markers in combination with HPV testing may offer a full molecular screening strategy to the many HIV-infected women who are also hrHPV positive.

Cited by 38 publications

References 34 publications

Virtues and Weaknesses of DNA Methylation as a Test for Cervical Cancer Prevention

Virtues and Weaknesses of DNA Methylation as a Test for Cervical Cancer Prevention

Detection of cervical intraepithelial neoplasia with HPVE6/E7 mRNA among women with atypical squamous cells of unknown significance

Human papillomavirus-associated anal and cervical cancers in HIV-infected individuals

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