Selection of women at risk for cervical cancer in an HIV-infected South African population

Zummeren, Marjolein van; Kremer, Wieke W.; Aardt, M.C. Van; Breytenbach, Erika; Richter, Karin Louise; Rozendaal, Lawrence; Witte, Birgit I.; Strooper, Lise M.A. De; Hesselink, Albertus T.; Heideman, Daniëlle A.M.; Snijders, Peter J.F.; Steenbergen, Renske D.M.; Dreyer, Greta; Meijer, Chris J.L.M.

doi:10.1097/qad.0000000000001583

Cited by 21 publications

(34 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies described a relationship between HIV and hypermethylation of host cell genes, resulting from an upregulation of DNA methyltransferase expression and activity in HIV‐infected cells . This may explain the rather low CIN3 + specificity of 49.6% detected in our previous study analysing the methylation marker panel CADM1, MAL, and miR124‐2 . Also in this study, the methylation levels for ASCL1 , LHX8 and ST6GALNAC5 were relatively high in control samples of HIV‐infected women compared to HIV‐uninfected women.…”

Section: Discussioncontrasting

confidence: 48%

“…Median age was 41 [interquartile range (IQR): 35 to 46 years] in the cohort of WLHIV and 44 years (IQR: 34 to 51 years) in the referral population. Detailed characteristics, inclusion criteria and study procedures of this study have been described previously . Written informed consent was obtained from all participants.…”

Section: Methodsmentioning

confidence: 99%

“…Primary hrHPV testing is currently the preferred method for cervical screening, irrespective of resource settings or HIV‐prevalence . However as most infections are self‐limiting and do not cause cervical lesions, hrHPV testing has limited specificity , particularly in WLHIV . Therefore, subsequent triage testing of hrHPV positive women is needed to distinguish women with underlying high‐grade cervical disease from women with transient infections .…”

Section: Introductionmentioning

confidence: 99%

“…Assays detecting hypermethylation are objective and can be applied on various specimen types, including self‐collected cervical material . Multiple genes have been identified as possible targets for cervical precancer and cancer detection, but few have been evaluated in WLHIV . We previously showed that methylation analysis of CADM1 , MAL and miR124‐2 genes in cervical scrapes from hrHPV positive WLHIV is an acceptable triage tool, which detects all cervical carcinomas and the majority of CIN3 .…”

Section: Introductionmentioning

confidence: 99%

“…Multiple genes have been identified as possible targets for cervical precancer and cancer detection, but few have been evaluated in WLHIV . We previously showed that methylation analysis of CADM1 , MAL and miR124‐2 genes in cervical scrapes from hrHPV positive WLHIV is an acceptable triage tool, which detects all cervical carcinomas and the majority of CIN3 . However, specificity of this marker panel when evaluated as a primary screening tool, without prior hrHPV testing, was limited.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Detection of hypermethylated genes as markers for cervical screening in women living with HIV

et al. 2018

Self Cite

View full text Add to dashboard Cite

IntroductionTo evaluate the performance of hypermethylation analysis of ASCL1,LHX8 and ST6GALNAC5 in physician‐taken cervical scrapes for detection of cervical cancer and cervical intraepithelial neoplasia (CIN) grade 3 in women living with HIV (WLHIV) in South Africa.MethodsSamples from a prospective observational cohort study were used for these analyses. Two cohorts were included: a cohort of WLHIV who were invited for cervical screening (n = 321) and a gynaecologic outpatient cohort of women referred for evaluation of abnormal cytology or biopsy proven cervical cancer (n = 108, 60% HIV seropositive). Cervical scrapes collected from all subjects were analysed for hypermethylation of ASCL1,LHX8 and ST6GALNAC5 by multiplex quantitative methylation specific PCR (qMSP). Histology endpoints were available for all study subjects.ResultsHypermethylation levels of ASCL1,LHX8 and ST6GALNAC5 increased with severity of cervical disease. The performance for detection of CIN3 or worse (CIN3+) as assessed by the area under the receiver operating characteristic (ROC) curves (AUC) was good for ASCL1 and LHX8 (AUC 0.79 and 0.81 respectively), and moderate for ST6GALNAC5 (AUC 0.71). At a threshold corresponding to 75% specificity, CIN3+ sensitivity was 72.1% for ASCL1 and 73.8% for LHX8 and all samples from women with cervical cancer scored positive for these two markers.ConclusionsHypermethylation analysis of ASCL1 or LHX8 in cervical scrape material of WLHIV detects all cervical carcinomas with an acceptable sensitivity and good specificity for CIN3+, warranting further exploration of these methylation markers as a stand‐alone test for cervical screening in low‐resource settings.

show abstract

Section: Discussioncontrasting

confidence: 48%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Detection of hypermethylated genes as markers for cervical screening in women living with HIV

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

DNA methylation markers have universal prognostic value for anal cancer risk in HIV‐negative and HIV‐positive individuals

et al. 2021

Self Cite

View full text Add to dashboard Cite

Anal cancer has increasing incidence and is preceded by high-grade anal intraepithelial neoplasia (HGAIN; AIN2-3). Previously, we identified and validated several methylation markers for accurate detection of anal cancer and HGAIN with cancer risk in HIV-positive (HIV+) men-who-have-sex-with-men (MSM). This study aimed to evaluate these markers in HIV-negative risk groups. A cross-sectional series of 176 tissue samples of anal cancer, AIN3, AIN2, AIN1, and control biopsies obtained in HIV-negative women and men was tested for six methylation markers (ASCL1, LHX8, SST, WDR17, ZIC1, ZNF582). Accuracy for detection of AIN3 and cancer (AIN3+) was determined by univariable and multivariable mixed-effect ordinal logistics regression. Methylation levels of all markers increased with increasing severity of disease (p<0.0001) and were comparable to results in HIV+ MSM. All markers showed high accuracy for AIN3+ detection (AUC 0.83-0.86). The optimal marker panel (ASCL1 and ZIC1; AUC=0.85 for AIN3+), detected 98% of cancers at 79% specificity. In conclusion, DNA methylation markers show a high diagnostic performance for AIN3+ detection in HIV+ and HIV-negative risk groups, justifying broad application of methylation analysis for anal cancer prevention programs.

show abstract

DNA methylation as a triage tool for cervical cancer screening – A meeting report

Burdier,

Waheed,

Nedjai

et al. 2024

Preventive Medicine Reports

View full text Add to dashboard Cite

Selection of women at risk for cervical cancer in an HIV-infected South African population

Abstract: In this HIV-infected South African population, stratifying hrHPV-positive women with reflex methylation analysis detects all cervical carcinomas and yields an acceptable sensitivity and specificity for CIN3+.

Cited by 21 publications

References 53 publications

Detection of hypermethylated genes as markers for cervical screening in women living with HIV

Detection of hypermethylated genes as markers for cervical screening in women living with HIV

DNA methylation markers have universal prognostic value for anal cancer risk in HIV‐negative and HIV‐positive individuals

DNA methylation as a triage tool for cervical cancer screening – A meeting report

Contact Info

Product

Resources

About