Performance of human papillomavirus E6/E7 mRNA assay for primary cervical cancer screening and triage: Population-based screening in China

Abstract

ObjectiveCervical cancer screening is very important in the prevention and treatment of cervical cancer. In China, the cervical screening strategy needs to be improved. To explore a suitable cervical screening strategy in China, we evaluated the performance of the human papillomavirus (HPV) E6/E7 mRNA (Aptima HPV (AHPV)) assay in primary screening and different triage strategies for women undergoing routine cervical screening.MethodsA total of 10,002 women aged 35 to 65 years of age were recruited in Liaoning Province and Qingdao City, China. Specimens were tested by liquid-based cytology (LBC) and the AHPV assay, and women who tested positive on any test were referred for colposcopy. Genotyping was performed on all high-risk HPV (HR-HPV)-positive samples. Test characteristics were calculated based on histological review.ResultsWe identified 109 women with high-grade squamous intraepithelial lesion or worse (HSIL+), including six with cervical cancer. The sensitivity of AHPV was clearly higher than that of LBC (92.7 [95% CI: 87.2, 97.2] vs. 67.9 [95% CI: 59.6, 76.1], p < 0.001). The specificity of AHPV was 93.0 (95% CI: 92.5, 93.5), which was lower than that of LBC (95.2 [95% CI: 94.8, 95.6], p < 0.001). There was no statistical difference between the positive predictive value of AHPV and LBC (13.5 [95% CI: 11.2, 16.2] vs. 14.3 [95% CI: 11.4, 17.6], p = 0.695). The difference of area under the curve (AUC) values between the AHPV test (0.928 [95% CI: 0.904, 0.953]) and LBC test (0.815 [95% CI: 0.771, 0.860]) in detecting HSIL+ was statistically significant (p < 0.001). Finally, among the three triage strategies, both the sensitivity (73.4 [95% CI: 65.1, 81.7]) and AUC (0.851 [95% CI: 0.809, 0.892]) of AHPV genotyping with reflex LBC triage were the greatest.ConclusionIn summary, the AHPV assay is both specific and sensitive for detecting HSIL+ and may be suitable for use in primary cervical cancer screening in China. AHPV genotyping with reflex LBC triage may be a feasible triage strategy.

Diagnostic value of high-risk HPV E6/E7 mRNA in patients with ASCUS Analysis of pathogenicity of HPV in patients with ASCUS

“…In 2013, ASCCP recommended the HPV DNA test as a basis for the management of patients with ASCUS, but its speci city was low, and the falsepositive rate was high. It was later reported that, compared with HPV DNA detection, HPV E6/E7 mRNA detection has high sensitivity and good speci city in high-grade cervical precancerous lesions, and it can be used as an effective means of further diagnosing patients with ASCUS [4][5][6].…”

The value of high-risk HPV E6/E7 mRNA test positivity with NILM cytology in detecting cervical squamous intraepithelial lesions and cervical cancer

“…Compared with HPV DNA testing using a noninferiority scoring method, HPV E6/E7 mRNA testing passed the cross-sectional clinical and reproducibility requirements of international CIN2 + detection HPV testing [12,13]. As a result, the number of patients who use E6/E7 mRNA for HPV testing is increasing yearly in China [14][15][16]; however, there is a lack of uniform clinical standards and guidelines for the management of HPV E6/E7 mRNA-positive patients, and an increasing number of patients who are positive for genotypes other than 16 and 18/45 are being referred for colposcopy and cervical biopsy. As a result, a major study evaluating triage techniques for different genotypes of HPV E6/E7 mRNA positivity in women with normal liquid-based cytology is needed.…”