Aptima HPV E6/E7 mRNA and cytology cross-sectional performance as primary screening tests for detection of high-grade cervical lesions in HIV positive and negative women in South Africa.

Objective: To assess the performance of APTIMA HPV E6/E7 mRNA assay (AHPV) with HPV 16 and 18/45 genotyping (AHPV-GT) and cytology in detecting cervical cancer and precancer in HIV positive and negative women in South Africa.

Methods: A multicentre cross-sectional study was performed in women aged 25-64 (n = 992) with cytology and AHPV with AHPV-GT reflex testing. All screen-positive and a random subset of screen-negative women were referred for colposcopy and biopsy.

Results: On cytology, low-grade squamous intraepithelial lesion (LSIL) or higher was found in 9.7% of HIV negative and 35.8% of HIV positive women. HPV mRNA positivity was 19.5% (4.4% HPV 16, 2.8% HPV 18/45, and 6.9% other high-risk HPV) in HIV negative women, compared to 45.8% (9.4% HPV 16, 9.7% HPV 18/45, and 27.6% other high-risk HPV) in HIV positive women The prevalence of histological abnormalities in HIV negative vs HIV positive women was 24.3 vs 46.0% for cervical intraepithelial neoplasia (CIN) 2+, 10.2 vs 24.1% for CIN3+, and 1.4 vs 2.4% for invasive squamous cell carcinoma. AHPV sensitivity for detection of CIN3 + performed the best: 69.0% (95% confidence interval (CI) 56.8-81.1) in HIV negative vs 81.4% (95% CI 73.7-89.0) in HIV positive women, followed by ASCUS + (atypical squamous cells of undetermined significance) cytology: 58.6% (95% CI 45.7-71.6) vs 76.5% (95% CI 68.1-84.8). The best positive predictive value for CIN2 + was for AHPV-GT16, followed by AHPV-GT16,18/45 and cytology LSIL+: HIV-negative women 84.0% (95% CI 68.9-99.1); 76.9% (95% CI 63.3-90.6); 75.0% (95 CI% 61.2-88.9) and HIV-positive women 92.5% (95% CI 84.1-100); 86.8% (95% CI 79.1-94.6); 84.0% (95% CI 77.6-90.3).

Conclusion: Significantly more HPV infection and cytological/histological abnormalities and advanced disease were seen in HIV positive women. The lower than expected clinical sensitivities of all screening tests are comparable to HPV DNA sensitivities reported in similar populations. AHPV with AHPV-GT performed better than cytology as a screening and triage test.