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1.
AIDS ; 36(7): 953-961, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35152224

RESUMO

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.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Metilação de DNA , Infecções por HIV , Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Feminino , Seguimentos , Infecções por HIV/complicações , Humanos , Proteínas com Homeodomínio LIM/genética , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Estudos Prospectivos , Fatores de Transcrição/genética , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/cirurgia , Displasia do Colo do Útero/genética , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/cirurgia
2.
AIDS ; 33(13): 2035-2042, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31385866

RESUMO

OBJECTIVE: To determine the performance of molecular screening strategies for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in comparison with cytology screening in women living with HIV. DESIGN: Post-hoc analysis using data from a South African study cohort. METHODS: Cytology and human papillomavirus (HPV)-based strategies were evaluated, including single test and FAM19A4/miR124-2 methylation triage strategies. Participants underwent cytology screening and a colposcopy-directed biopsy. Valid results on cytology, HPV status, 16/18 genotyping and histology were available for 318 women. Detection of HPV and FAM19A4/miR124-2 hypermethylation was performed on DNA from cervical scrapes. Histological diagnosis of CIN3+ was used as outcome. RESULTS: Cytology provided highest specificity (91.6%), but lowest sensitivity (59.3%), whereas a single HPV test provided highest sensitivity (83.1%), but lowest specificity (66.4%). Combining cytology with methylation did not improve the performance compared with cytology alone: a slight increase in sensitivity was seen, at the cost of a decrease in specificity. Triage of high-risk HPV positive women with methylation increased specificity (76.1%) compared with a single HPV or cytology test, while maintaining acceptable sensitivity (72.9%). Similar performance was observed for HPV16/18 with methylation triage (sensitivity 79.7%, specificity 74.8%). The number of women needed to refer to detect one CIN3+ ranged from 1.5 (cytology) to 2.6 (single HPV test). CONCLUSION: Molecular screening strategies using HPV, with or without HPV16/18 genotyping, and FAM19A4/miR124-2 methylation have higher sensitivity with an acceptable loss in specificity compared with current cytology screening and are efficient for the detection of CIN3+ in South African women living with HIV.


Assuntos
Citocinas/genética , Infecções por HIV/complicações , MicroRNAs/genética , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Colposcopia , Metilação de DNA , Feminino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/genética , Valor Preditivo dos Testes , Medição de Risco , África do Sul , Neoplasias do Colo do Útero/genética , Displasia do Colo do Útero/genética
3.
AIDS ; 31(14): 1945-1953, 2017 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-28692545

RESUMO

OBJECTIVE: Cervical cancer is the leading cause of cancer-related death in women in South Africa. This study evaluates DNA methylation levels in cervical (pre)cancer and aims to assess the value of high-risk human papillomavirus (hrHPV) testing and methylation analysis, alone or in combination, on physician-taken cervical scrapes to detect cervical cancer, and cervical intraepithelial neoplasia grade 3 (CIN3) in an HIV-infected South African population. DESIGN: Prospective observational multicentre cohort study. METHODS: Women from a cohort of women living with HIV (n = 355) and a referral cohort (n = 109, 60% HIV seropositive) were included. Cervical scrapes were collected for hrHPV testing and methylation analysis of cell adhesion molecule 1, T-lymphocyte maturation-associated protein, and microRNA124-2 genes. Histologic endpoints were available for all participants. Performance for detection of CIN3 or worse (CIN3+) was determined in the cohort of women living with HIV and different testing strategies were compared. RESULTS: HrHPV and methylation positivity rates increased with severity of cervical disease in the two study cohorts, each reaching 100% in samples of women with carcinoma. HrHPV testing showed a sensitivity for CIN3+ of 83.6%, at a specificity of 67.7%. Methylation analysis showed a comparable CIN3+ sensitivity of 85.2%, but a significantly lower specificity of 49.6%. HrHPV testing with reflex methylation analysis showed a CIN3+ sensitivity of 73.8%, at a specificity of 81.5%. CONCLUSION: 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+.


Assuntos
Infecções por HIV/complicações , Programas de Rastreamento/métodos , Técnicas de Diagnóstico Molecular/métodos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Molécula 1 de Adesão Celular/genética , Feminino , Humanos , Metilação , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas Proteolipídicas Associadas a Linfócitos e Mielina/genética , Papillomaviridae/classificação , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Estudos Prospectivos , Sensibilidade e Especificidade , África do Sul
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