Yu Dai

The Distribution of HR‐HPV E6/E7 DNA and mRNA by Histological Grade and the Clinical Performance for Detection of Cervical Cancer and Precancer

ABSTRACT High‐risk human papillomavirus (HR‐HPV) testing, utilizing both DNA and RNA methods, offers enhanced sensitivity compared to cytology for detecting high‐grade cervical intraepithelial neoplasia (CIN2+). Meanwhile, HR‐HPV E6 and E7 mRNAs are more likely to differentiate the transient infection from the persistent than DNA. Aptima HPV can not only detect HPV mRNA but also HPV DNA though it is much more efficient at detecting HPV RNA than DNA. Currently, there are few studies on the distribution of HPV E6 and E7 mRNA and DNA in the same individual. It is interesting to compare the clinical performance of the Onclarity and Aptima HPV assays and to assess variations in viral load across different histological grades at both DNA and mRNA levels. The analysis included 1607 women (902 from a cervical cancer screening population and 705 inpatients and outpatients), with cervical cytological samples tested using the Aptima and Onclarity HPV assays. Both assays demonstrated high agreement for HPV types 18/45 and 16. Signal‐to‐cutoff (S/CO) values and Ct values for various HR‐HPV types increased with histological severity from normal tissue to cancer. Notably, HPV18 Ct values exceeded those for HPV16 and 45 in women with ≥ CIN1 lesions but decreased sharply in cancer cases. Across the screening population, both assays showed similar sensitivity and predictive values for detecting CIN2+ lesions. The area under the curve (AUC) for CIN2+ and CIN3+ detection in the study population was robust (CIN2+: 0.880, 0.863; CIN3+: 0.881, 0.863). The DNA level for various HR‐HPV types increased with histological severity from normal tissue to cancer, which might impact the performance of Aptima HPV assay. Both assays showed similar sensitivity and predictive values for detecting CIN2+ lesions.

The Impact of Specific Sexually Transmitted Pathogens on Cervix: A Prospective Study Based on Cervical Cancer Screening Cohort

ABSTRACT Previous studies showed the association between sexually transmitted infections (STIs) and cervical lesions remains ambiguous. This study was conducted among 8371 women from a screening cohort. Seven specific sexually transmitted pathogens (STPs), including one viral [high‐risk human papillomavirus (hrHPV), low‐risk HPV (lrHPV)], five bacterial [Ureaplasma parvum (UP), Mycoplasma hominis (MH), Ureaplasma urealyticum (UU), Chlamydia trachomatis (CT), and Mycoplasma genitalium (MG)], and one parasitic [Trichomonas vaginalis (TV)] pathogen, were tested by Next Generation Sequencing assay using well‐stored baseline samples. Odds ratios (ORs) for incident cervical lesions with different STPs were calculated by Logistic Regression analysis. Within 3‐year follow‐up, 133 and 72 participants were diagnosed with histopathological cervical intraepithelial neoplasia grade 1 (CIN1) and CIN2+, respectively. The adjusted ORs (aORs) of atypical squamous cells of undetermined significance or worse (ASC‐US+) for women with hrHPV, lrHPV, UP, MH, TV, CT, and MG infections were 2.62 (95% CI: 2.19–3.13), 1.94 (95% CI: 1.55–2.43), 1.48 (95% CI: 1.26–1.74), 1.47 (95% CI: 1.25–1.73), 1.65 (95% CI: 1.27–2.15), 1.26 (95% CI: 0.79–2.01) and 2.33 (95% CI: 1.41–3.85), respectively. The aORs of cytological high‐grade squamous intraepithelial lesions (HSIL) for women with hrHPV, TV, and MG infections were 13.01 (95% CI: 5.78–29.31), 3.48 (95% CI: 1.38–8.75), and 5.87 (95% CI: 1.58–21.77). The aORs of CIN1 for hrHPV, lrHPV, and MH were 6.88(95% CI: 4.79–9.90), 2.04(95% CI: 1.29–3.14), and 1.47(95% CI: 1.02–2.11). The aOR of CIN2+ for women with hrHPV infection was 17.56 (95% CI: 10.31–29.92), no significance was observed for CIN2+ with non‐hrHPV STIs. Specific STP infections were significantly associated with subsequent cervical cytological ASC‐US+ (hrHPV, lrHPV, UP, MH, TV, and MG) and HSIL (hrHPV, TV, and MG). Infection with lrHPV and MH could increase the CIN1 risk in future though no obvious CIN2+ risk elevation was observed.