Predicting cervical intraepithelial neoplasia recurrence in HIV-infected and -noninfected women by detecting aberrant promoter methylation in the CDH1, TIMP3, and MGMT genes

Lodi, Claudia Teixeira da Costa; Michelin, Márcia Antoniazi; Lima, Maria Inês Miranda; Murta, Eddie Fernando Cândido; Braga, Letícia da Conceição; Montes, Leticia Nunes; Melo, Victor Hugo

doi:10.1007/s00404-018-4899-x

Cited by 4 publications

(4 citation statements)

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“…Several other host cell methylation markers have been studied in WLHIV [28–31,47] and similar performance compared with HPV with FAM19A4/miR124-2 methylation triage has been shown for triage of high-risk HPV positive women with the marker panel CADM1, MAL and miR124-2 by us and others [26,32]. More recently, Kelly et al [27] showed that methylation of EPB41L3 increased with cervical disease severity in a South African cohort of WLHIV, but the accuracy of this marker for the detection of CIN3 and cervical cancer is difficult to derive from these data, as the threshold for methylation positivity was neither determined nor validated.…”

Section: Discussionmentioning

confidence: 99%

The use of molecular markers for cervical screening of women living with HIV in South Africa

Kremer

Zummeren

Breytenbach

et al. 2019

Aids

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Section: Discussionmentioning

confidence: 99%

The use of molecular markers for cervical screening of women living with HIV in South Africa

Kremer

Zummeren

Breytenbach

et al. 2019

Aids

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“…Of such studies, all studies were eligible to calculate the hypermethylation rates of MGMT . A total of 2933 patients with SIL or CC from 25 studies (6 case-only studies[34, 43, 46, 48, 49, 51] and 19 case-control studies) were eligible to estimate the association of MGMT methylation status with the clinicopathological features. For most of these 25 studies (17 of 25), the detection of MGMT promoter methylation was performed by methylation-specific PCR (MSP).…”

Section: Resultsmentioning

confidence: 99%

Associations of MGMT promoter hypermethylation with squamous intraepithelial lesion and cervical carcinoma: A meta-analysis

2019

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BackgroundIn this research, an meta-analysis was performed for assessment of the associations between O6-methyguanine-DNA methyltransferase (MGMT) promoter hypermethylation possessing low-grade intraepithelial lesion (LSIL), high-grade intraepithelial lesion (HSIL), cervical cancer (CC), and clinicopathological characters of CC.MethodsLiterature selection were conducted through searching PubMed, Web of science, EMBASE, China National Knowledge Infrastructure and Wanfang databases (up to November 2018). An assessment of associations between MGMT methylation and LSIL, HSIL, CC risk and clinicopathological characteristics was performed through pooled odds ratios (ORs) with relevant 95% confidence intervals (CIs). Subgroup analyses, meta-regressions and Galbraith plots were conducted to conduct an exploration on the possible sources of heterogeneity. The genome-wide DNA methylation array studies were extracted from Gene Expression Omnibus (GEO) databases for validation of these outcomes.ResultsIn this meta-analysis of 25 published articles, MGMT hypermethylation gradually elevated the rates among control group (12.16%), LSIL (20.92%), HSIL (36.33%) and CC (41.50%) specimens. MGMT promoter methylation was significant associated with the increased risk of LSIL by 1.74-fold (P<0.001), HSIL by 3.71-fold (P<0.001) and CC by 7.08-fold (P<0.001) compared with control. A significant association between MGMT promoter methylation with FIGO stage was also found (OR = 2.81, 95% CI: 1.79–4.41, p<0.001). The results of GEO datasets showed that 5 CpG sites in MGMT with a great diagnostic value for the screening of cervical cancer.ConclusionThe meta-analysis indicated the association between MGMT promoter hypermethylation and squamous intraepithelial lesion and cervical cancer. MGMT methylation detection might have a potential value to be an epigenetic marker for the clinical diagnosis of cervical cancer.

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“…Although host-cell DNA methylation analysis has been suggested as a biomarker for the detection of rCIN [46,47], very limited evaluations for posttreatment monitoring have been performed. Our findings are in line with evaluations of the SIMONATH-trial, in which Uijterwaal et al [5] found a 2% rCIN3 risk in HIVnegative women with a CADM1/MAL methylationnegative follow-up test 6 or 12 months after Fig.…”

Section: Discussionmentioning

confidence: 99%

Posttreatment monitoring by ASCL1/LHX8 methylation analysis in women with HIV treated for cervical intraepithelial neoplasia grade 2/3

Vink

Kremer

Lissenberg‐Witte

et al. 2022

Aids

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Objective:Women with HIV (WWH) have an increased risk to develop recurrent cervical intraepithelial neoplasia grade 2/3 (rCIN2/3) after treatment compared with HIV-negative women. Therefore, appropriate posttreatment monitoring of WWH is important. This study evaluates the performance of ASCL1 and LHX8 methylation analysis as posttreatment monitoring test in WWH treated for CIN2/3, as alternative to cytology or human papillomavirus (HPV) as follow-up test.Design:Prospective observational cohort study.Methods:WWH treated for CIN2/3 by large loop excision of the transformation zone (LLETZ) (n = 61) were invited for follow-up study visits at 1, 2.5 and 4 years after baseline. Baseline and follow-up cervical scrapes were tested for cytology, HPV and DNA methylation of ASCL1 and LHX8 genes. The performance of these strategies for the detection of rCIN2/3 was evaluated in the first follow-up cervical scrape.Results:Thirteen (21.3%) rCIN2/3 lesions were detected within 4 years of follow-up. In women without rCIN2/3 in follow-up, methylation levels of ASCL1 and LHX8 decreased significantly after LLETZ treatment (P = 0.02 and 0.007, respectively). In women with rCIN2/3, methylation levels remained high after LLETZ treatment. The 4-year rCIN2/3 risk was 4.9% (95% CI: 0.6–16.5) for ASCL1/LHX8-negative women, 8.1% (95% CI: 1.7–21.9) for HPV-negative women and 7.7% (95% CI: 2.1–18.5) for cytology-negative women.Conclusion:A negative ASCL1/LHX8 methylation test in follow-up is associated with a low rCIN2/3 risk and could serve as an objective test of cure and well tolerated alternative for HPV and/or cytology screening in the posttreatment monitoring of WWH.

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Predicting cervical intraepithelial neoplasia recurrence in HIV-infected and -noninfected women by detecting aberrant promoter methylation in the CDH1, TIMP3, and MGMT genes

Abstract: CIN recurrence was associated with glandular involvement and compromised margins in cone biopsy and HIV infection. The presence of CpG islands hemimethylation in TIMP3 and MGMT genes is a promising triage method in CIN recurrence.

Cited by 4 publications

References 36 publications

The use of molecular markers for cervical screening of women living with HIV in South Africa

The use of molecular markers for cervical screening of women living with HIV in South Africa

Associations of MGMT promoter hypermethylation with squamous intraepithelial lesion and cervical carcinoma: A meta-analysis

Posttreatment monitoring by ASCL1/LHX8 methylation analysis in women with HIV treated for cervical intraepithelial neoplasia grade 2/3

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