Referral population studies underestimate differences between human papillomavirus assays in primary cervical...

Area of Science:

• Gynecologic Oncology
• Molecular Diagnostics
• Public Health Screening

Background:

• Cervical cancer screening relies on cytology and human papillomavirus (HPV) testing.
• Primary screening involves predominantly cytologically normal women, while referral populations consist of abnormal cases.
• Understanding HPV assay performance in diverse populations is crucial for accurate cervical cancer detection.

Purpose of the Study:

• To evaluate the representativeness of cytologically abnormal women in uncovering differences between HPV assays.
• To compare HPV assay performance in primary screening versus referral populations.
• To assess the impact of cytological status on HPV assay signal strength and discordance.

Main Methods:

• 4997 women underwent SurePath® cytology and testing with four HPV assays: Hybrid Capture 2 (HC2), cobas, CLART, and APTIMA.
• Signal strengths of HPV infections and HPV-positive high-grade cervical intraepithelial neoplasia (≥CIN2) were analyzed from baseline samples.
• Test result discordance was calculated as the proportion of HPV-positive samples not confirmed by all four assays.

Main Results:

• Median HPV signal strengths were significantly weaker in normal cytology compared to abnormal cytology across all tested assays.
• The four HPV assays exhibited higher rates of discordant results in cytologically normal women than in abnormal cases.
• The relative frequency of discordance in detecting HPV infections was 0.39 in abnormal versus normal cytology.

Conclusions:

• Referral population studies, often lacking sufficient normal cytology cases, may underestimate HPV assay differences.
• Primary screening populations provide a more comprehensive assessment of HPV assay performance.
• Accurate HPV assay evaluation requires inclusion of a substantial number of cytologically normal individuals.