Posttreatment monitoring by ASCL1/LHX8 methylation analysis in women with HIV treated for cervical intraepithelial neoplasia grade 2/3. (1st June 2022)

• Record Type: Journal Article
• Authors: Vink, Frederique J.; Steenbergen, Renske D.M.; Kremer, Wieke W.; Lissenberg-Witte, Birgit I.; Heideman, Daniëlle A.M.; Bleeker, Maaike C.G.; van Zummeren, Marjolein; Breytenbach, Erika; Visser, Cathy; Lukhwareni, Azwidowi; Meijer, Chris J.L.M.; Dreyer, Greta
• Is Part Of: AIDS. Volume 36:Number 7(2022)
• Page Start: 953
• Page End: 961
• Publication Date: 2022-06-01
• Subjects: cytology -- DNA methylation marker -- HIV -- human papilloma virus -- recurrent cervical intraepithelial neoplasia; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000003197
• Languages: English
• ISSNs: 0269-9370

Abstract

Abstract : 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.