Genotype-Specific HPV E6/E7 mRNA Triage Improves Risk Stratification and Reduces Referrals in DNA-Positive...

Area of Science:

• Gynecology
• Oncology
• Molecular Diagnostics

Background:

• Human papillomavirus (HPV) DNA-positive women with atypical squamous cells of undetermined significance (ASC-US)/low-grade squamous intraepithelial lesion (LSIL) cytology present a heterogeneous risk profile.
• Efficient triage strategies are crucial for managing these patients in cervical screening programs.

Purpose of the Study:

• To evaluate the performance of a genotype-specific 7-type HPV E6/E7 mRNA assay (PreTect HPV-Proofer 7) for risk stratification in HPV-positive women with ASC-US/LSIL cytology.
• To assess the assay's impact on colposcopy referral rates and screening efficiency in a real-world setting.

Main Methods:

• A real-world quality-assurance cohort at Nordland Hospital included 175 HPV-positive women with ASC-US/LSIL cytology and complete follow-up data.
• A genotype-specific 7-type HPV E6/E7 mRNA assay was used to test residual liquid-based cytology samples.
• Performance metrics including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for CIN2+ and CIN3+ were calculated. Referral simulation was performed.

Main Results:

• Overall, 44.6% of women were mRNA-positive. The assay demonstrated a sensitivity of 63.4% and specificity of 61.2% for CIN2+.
• mRNA-positive women had a significantly higher risk of CIN2+ (33.3%) compared to mRNA-negative women (15.5%).
• mRNA-guided triage simulation reduced baseline colposcopy referrals by 55% and decreased colposcopies per detected CIN2+ by approximately 30%.

Conclusions:

• Genotype-specific HPV E6/E7 mRNA testing improves risk stratification in HPV-positive women with ASC-US/LSIL cytology.
• This assay has the potential to increase cervical screening efficiency by optimizing colposcopy referrals.
• Further evaluation is warranted to confirm these findings in broader populations.