Objectives We investigated the role of molecular markers in cervical cancer screening for South African women living with HIV (WLHIV).

Methods South African WLHIV underwent cervical screening and colposcopy-directed biopsy with molecular screening. Data included cytology, HPV (high-risk), HPV (16/18) and histology. Detection of FAM19A4/miR124–2 hypermethylation was performed on DNA isolated from cervical scrapes. Diagnostic performance of cytology and HPV tests alone and combined with FAM19A4/miR124–2 hypermethylation was determined.

Results 285 women were included in the analyses. Cytology provided the highest specificity (91.6%), but lowest sensitivity (59.3%), HPV (high-risk) provided the highest sensitivity (83.1%), but lowest specificity (66.4%). Combining cytology with methylation did not improve the performance of cytology alone, but triage of HPV (high-risk) with methylation, increased specificity (76.1%) while maintaining an acceptable sensitivity (72.9%). Similar performance was observed for HPV (16/18) with methylation triage (sensitivity 79.7%, specificity 74.8%). Number referred per CIN3+ was lowest for cytology (1.5), but only slightly higher for HPV (high-risk) or HPV (16/18) with methylation triage (2.3 and 2.2).

Conclusions We report promising results using molecular triage of HPV positive WLHIV with methylation markers regarding sensitivity and specificity for CIN 3+.