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) (n¼61) 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 (P¼0.02 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 cytologynegative
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.
