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

AIDS. 2022 Jun 1;36(7):953-961. doi: 10.1097/QAD.0000000000003197. Epub 2022 Feb 15.

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.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors* / genetics
  • DNA Methylation*
  • Female
  • Follow-Up Studies
  • HIV Infections* / complications
  • Humans
  • LIM-Homeodomain Proteins / genetics
  • Papillomaviridae / genetics
  • Papillomavirus Infections* / diagnosis
  • Prospective Studies
  • Transcription Factors / genetics
  • Uterine Cervical Dysplasia* / genetics
  • Uterine Cervical Dysplasia* / pathology
  • Uterine Cervical Dysplasia* / surgery
  • Uterine Cervical Neoplasms* / diagnosis
  • Uterine Cervical Neoplasms* / genetics
  • Uterine Cervical Neoplasms* / surgery

Substances

  • ASCL1 protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • LIM homeobox protein 8
  • LIM-Homeodomain Proteins
  • Transcription Factors