Women living with HIV (WLHIV) are at increased risk for developing cervical intraepithelial neoplasia (CIN) and cervical cancer. Countries with a high HIV incidence, such as South Africa, often lack effective cervical cancer screening programs due to insufficient resources, lack of infrastructure and limited access to health care. Reliable tests for early cervical cancer and precancer detection that are suitable for this setting are urgently needed.
This study evaluates the performance of FAM19A4/miR124-2 methylation markers (QIAsure Methylation Test) on physician-taken cervical scrapes to detect cervical cancer and CIN grade 3 (CIN3) in WLHIV in South Africa.
Samples from a prospective observational multi-centre cohort study were used for this analysis. In this study, two cohorts were included: a cohort of WLHIV who were invited for cervical cancer screening (n=321) and a referral cohort consisting of women referred for further evaluation of a cervical abnormality in a gynaecologic outpatient department (n=108). Cervical scrapes collected from all subjects were used for methylation analysis of FAM19A4 and miR124-2 genes by the QIAsure Methylation Test. High-risk HPV (hrHPV) status and histology endpoints were available for all subjects. Methylation levels in samples of HIV seropositive women were compared to samples of HIV seronegative women. Performance of reflex methylation analysis among hrHPV-positive women for detection of CIN3 or worse (CIN3+) was determined in the cohort of WLHIV.
Methylation levels increased with severity of cervical disease in both study cohorts and were above the set threshold in all samples of women with cervical cancer. When compared to samples of HIV seronegative women, methylation levels in samples of WLHIV were significantly higher in all histology groups except cervical cancer. Stratifying hrHPV-positive women with reflex methylation analysis showed a CIN3+ sensitivity of 72.9% and a specificity of 76.1%.
In this South African cohort of WLHIV, reflex methylation analysis of hrHPV-positive cervical scrapes detects all cervical carcinomas and has an acceptable sensitivity and specificity for CIN3+ detection. The applicability of the test on self-collected samples and its objective nature makes it a promising screening tool for low-resource settings.