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

• Published in: AIDS (London) Vol. 36; no. 7; pp. 953 - 961
• Main 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
• Format: Journal Article
• Language: English
• Published: England 01.06.2022
• Subjects: Basic Helix-Loop-Helix Transcription Factors - genetics; Cervical Intraepithelial Neoplasia - genetics; Cervical Intraepithelial Neoplasia - pathology; Cervical Intraepithelial Neoplasia - surgery; DNA Methylation; Female; Follow-Up Studies; HIV Infections - complications; Humans; Papillomaviridae - genetics; Papillomavirus Infections - diagnosis; Prospective Studies; Uterine Cervical Neoplasms - diagnosis; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - surgery
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/QAD.0000000000003197

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. Prospective observational cohort study. 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. 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. 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.