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High-Risk Human Papillomavirus Positive-Negative-Positive Infection Pattern Revealed Infection Below the Screening
Nolwen Di Domizio, Channel Bertin1, Rajeev Ramanah2
1CHU Besançon, Centre National de Référence Papillomavirus, Besançon, France.
Journal of Lower Genital Tract Disease
|September 19, 2025
Summary
Rare positive-negative-positive patterns of high-risk human papillomavirus (HR-HPV) were observed. Most negative results with the Hybrid Capture 2 (HC2) assay were due to low viral load, indicating subclinical infection rather than latency.
Area of Science:
- Gynecology
- Virology
- Oncology
Background:
- Cervical cancer screening relies on detecting high-risk human papillomavirus (HR-HPV).
- The Hybrid Capture 2 (HC2) assay is a common screening tool for HR-HPV.
- Understanding HPV infection dynamics, including transient or low-titer infections, is crucial for accurate diagnosis and management.
Purpose of the Study:
- To characterize HR-HPV infections in women with a specific positive-negative-positive (PNP) screening pattern.
- To investigate the performance of a sensitive genotyping assay in detecting HPV in samples that were negative by HC2 assay but showed a PNP pattern.
Main Methods:
- Identified women with PNP HR-HPV results using the HC2 assay (2015-2021).
- Analyzed cervical smears from these women using a sensitive reverse line blot genotyping assay to detect 32 HPV genotypes.
- Compared genotyping results with HC2 assay results to understand discrepancies.
Main Results:
- A PNP HR-HPV infection pattern was identified in 29 out of 10,512 women (0.27%).
- A sensitive genotyping assay detected HPV in 93% of HC2-negative samples within the PNP group.
- Infections were linked to prior cervical treatments or represented persistent/transient low-titer infections, not latent HPV.
Conclusions:
- The PNP HR-HPV screening pattern is rare.
- HC2 assay negativity is often due to HPV detection below the assay's cutoff, indicating subclinical infections.
- The study did not find evidence of HPV latency, but rather low-titer, subclinical HPV infections.

