Methylation Levels of CADM1, MAL, and MIR124-2 in Cervical Scrapes for Triage of HIV-Infected, High-Risk HPV-Positive Women in Kenya.
J Acquir Immune Defic Syndr
; 70(3): 311-8, 2015 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-26473640
ABSTRACT
OBJECTIVES:
To evaluate the value of cervical cell methylation markers in screening HIV-infected women also positive for high-risk human papillomavirus (hrHPV).DESIGN:
Cross-sectional and prospective.METHODS:
Two hundred forty-eight HIV-infected hrHPV-positive women enrolled in a cervical cancer screening study in Nairobi, Kenya, had colposcopy-directed biopsy and histological diagnoses. Exfoliated cervical cells were used to measure methylation levels of the CADM1, MAL, and MIR124-2 genes using quantitative methylation-specific polymerase chain reaction. Methylation levels were summarized as cycle threshold (Ct) ratios compared with the ß-actin gene. Median Ct ratios were compared across histological diagnoses, with 95% confidence intervals calculated by bootstrapping. Methylation levels at 6 months were assessed in 128 women who remained hrHPV positive.RESULTS:
All 3 methylation markers showed significantly (P < 0.001) raised median Ct ratios in women with cervical intraepithelial neoplasia (CIN) grade 3 compared with women with a normal cervix. When markers were combined into a single test, the area under the receiver operating characteristic curve for prediction of CIN2 or worse (CIN2+) was 0.80. When the test was calibrated to have similar specificity, sensitivity of the combined tri-marker test for CIN2+ was comparable with cytology [atypical squamous cells of undetermined significance or worse] (89% and 95%, respectively) and superior to visual inspection with acetic acid (85% vs 70%) and HPV16/18 genotyping (65% vs 40%). Among women with no CIN2+ at baseline and persistent hrHPV at 6-month follow-up, MAL-m1 and MIR124-2 Ct ratios increased significantly.CONCLUSIONS:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Papillomaviridae
/
Imunoglobulinas
/
Moléculas de Adesão Celular
/
Infecções por HIV
/
Infecções por Papillomavirus
/
MicroRNAs
/
Proteínas Proteolipídicas Associadas a Linfócitos e Mielina
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
País/Região como assunto:
Africa
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article