Cervical Cytology and HPV16/18/45 mRNA Co-Testing Improve Risk Stratification in Routine Clinical Practice.

Area of Science:

• Gynecologic oncology
• Molecular diagnostics
• Public health

Background:

• Cervical cancer prevention relies on accurate risk stratification.
• Co-testing with cytology and HPV testing is a key strategy.
• Genotype-specific HPV mRNA assays offer potential for improved risk assessment.

Purpose of the Study:

• To evaluate the real-world effectiveness of co-testing using cervical cytology and a genotype-specific HPV E6/E7 mRNA assay (PreTect SEE).
• To assess the risk stratification capabilities of this co-testing approach in routine clinical practice.
• To identify high-risk patient subgroups for improved cervical cancer prevention.

Main Methods:

• Retrospective, registry-based cohort study.
• Inclusion of 116,217 eligible co-test samples (cytology and HPV mRNA).
• Passive follow-up for histological outcomes including CIN2+, CIN3+, and cervical cancer.

Main Results:

• Co-testing demonstrated a clear stepwise risk gradient across different test result combinations.
• Double-negative results (NILM/mRNA-) showed very low risks (CIN3+ 0.2%).
• Positive HPV mRNA results, even with normal cytology (NILM/mRNA+), indicated substantially higher risks (CIN3+ 13.0%), capturing significant CIN3+ and cancer cases.

Conclusions:

• Co-testing with cytology and a 3-type HPV mRNA assay provides robust clinical risk stratification.
• This method effectively identifies a small but high-risk subgroup among women with normal cytology.
• Genotype-specific HPV mRNA testing is a valuable adjunct to cytology in routine cervical cancer screening.