A DNA methylation approach using HPV16 was evaluated in 151 HPV16 positive WLHIV in Burkina Faso and South Africa enrolled in the HPV in Africa Research Partnership study. HPV16 infection was common in WLHIV with and without precancer, although prevalence of precancer was higher in women with HPV16 infection compared to those without HPV16 infection. DNA methylation of HPV16 L1/L2 genes did not distinguish women with and without cervical precancer, but HPV16 viral load was significantly higher in women with precancer compared to those without. In this study, HPV16 viral load (E6/E7) test had higher diagnostic accuracy to detect cervical precancer in women with HPV16 infection, compared to DNA methylation of HPV16.
To address the secondary objective, several meta-analyses were conducted during this study to evaluate the diagnostic accuracy of current and novel cervical cancer screening strategies in women living with HIV. In a meta-analysis of the diagnostic accuracy of cervical cancer screening strategies in WLHIV including 31 studies and 17,676 WLHIV which evaluated screen strategies (VIA, HPV-DNA tests, cervical cytology) and screen-triage (VIA, cytology, HPV16/18 genotyping in HPV positive women) strategies for precancer, VIA had variable sensitivity and specificity for precancer due to heterogeneity in study design and training and experience of operators. Less variability was observed for HPV-DNA based tests which had high sensitivity for precancer but low specificity which is possibly a reflection of the high prevalence of non-clinically relevant HR-HPV infections, thereby suggesting the need for a triage test for HPV positive women. Modifications to HPV tests to increase threshold for test positivity as well as restricted genotype approach increased specificity. In a separate meta-analysis of the evidence on diagnostic accuracy of currently available DNA methylation assays for precancer, 16,336 women in 43 studies provided data on the mostly studied human genes (CADM1, MAL, MIR-124-2, FAM19A4, POU4F3, EPB41L3, PAX1, SOX1) and HPV genotypes (HPV16 L1/L2 genes). Most (81%) studies evaluated methylation assays following a high-risk (HR)-HPV-positive or abnormal cytology result. As a triage test, DNA methylation has higher specificity than cervical cytology and higher sensitivity than HPV16/18 genotyping.
