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

Frederique J Vink, Renske D M Steenbergen, Wieke W Kremer, Birgit I Lissenberg-Witte, Daniëlle A M Heideman, Maaike C G Bleeker, Marjolein van Zummeren, Erika Breytenbach, Cathy Visser, Azwidowi Lukhwareni, Chris J L M Meijer, Greta Dreyer

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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.

Original languageEnglish
Pages (from-to)953-961
Number of pages9
JournalAIDS (London, England)
Issue number7
Early online date11 Feb 2022
Publication statusPublished - 1 Jun 2022


  • Cytology
  • DNA methylation marker
  • HIV
  • human papilloma virus
  • recurrent cervical intraepithelial neoplasia

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