Productive or Transforming? How Epithelial Compartmentalization of HPV DNA and E6/E7 Transcripts Shapes Cervical Screening Assay Performance
- 1Department of Pathology University of Cambridge Cambridge UK
Abstract
The human papillomavirus (HPV) life cycle is linked to epithelial cell differentiation, with viral genome amplification, E6/E7 transcription, and virion assembly spatially compartmentalized within the cervical epithelium. This organization is disrupted in transforming lesions. These fundamental observations determine what ‘bulk’ nucleic acid amplification tests (NAATs) of cervical exfoliates allow us to establish. DNA‐based assays sensitively report high‐risk HPV genome presence, which includes transient infections and virus particles. RNA‐based assays target the E6/E7 transcripts in transcriptionally active disease, which accounts for their slightly higher clinical specificity for high‐grade squamous intraepithelial lesions. No single assay defines both viral presence and disease significance, however. Cytology, p16/Ki‐67 dual stain, extended genotyping and host‐cell methylation interrogate complementary axes of risk with strong biological rationale. The loss of spatial information that limits bulk NAAT approaches matters most in mixed‐grade lesions and immunocompromised populations. Emerging spatial methods, AI‐assisted cytology and cervical cell‐lifts offer recovery of biological resolution.
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BibTeX
@article{schichl2026productive,
title = {{Productive or Transforming? How Epithelial Compartmentalization of HPV DNA and E6/E7 Transcripts Shapes Cervical Screening Assay Performance}},
author = {Konstanze Schichl and John Doorbar},
journal = {Journal of Medical Virology},
year = {2026},
month = oct,
doi = {10.1002/jmv.71196},
url = {https://doi.org/10.1002/jmv.71196},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Productive or Transforming? How Epithelial Compartmentalization of HPV DNA and E6/E7 Transcripts Shapes Cervical Screening Assay Performance
AU - Konstanze Schichl
AU - John Doorbar
PY - 2026
DA - 2026/10/27
JO - Journal of Medical Virology
DO - 10.1002/jmv.71196
UR - https://doi.org/10.1002/jmv.71196
AB - The human papillomavirus (HPV) life cycle is linked to epithelial cell differentiation, with viral genome amplification, E6/E7 transcription, and virion assembly spatially compartmentalized within the cervical epithelium. This organization is disrupted in transforming lesions. These fundamental observations determine what ‘bulk’ nucleic acid amplification tests (NAATs) of cervical exfoliates allow us to establish. DNA‐based assays sensitively report high‐risk HPV genome presence, which includes transient infections and virus particles. RNA‐based assays target the E6/E7 transcripts in transcriptionally active disease, which accounts for their slightly higher clinical specificity for high‐grade squamous intraepithelial lesions. No single assay defines both viral presence and disease significance, however. Cytology, p16/Ki‐67 dual stain, extended genotyping and host‐cell methylation interrogate complementary axes of risk with strong biological rationale. The loss of spatial information that limits bulk NAAT approaches matters most in mixed‐grade lesions and immunocompromised populations. Emerging spatial methods, AI‐assisted cytology and cervical cell‐lifts offer recovery of biological resolution.
SN - 0146-6615
SN - 1096-9071
ER -