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Extended Human Papillomavirus Genotyping to Predict Progression to High-Grade Cervical Precancer: A Prospective Cohort Study in the Southeastern United States
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Abstract
Background: High-risk human papillomavirus (hrHPV) testing is utilized in primary cervical cancer screening, generally along with cytology, to triage abnormalities to colposcopy. Most screening-based hrHPV testing involves pooled detection of any hrHPV or of HPV16/18. Cervical neoplasia progression risks based on extended hrHPV genotyping—particularly non-16/18 hrHPV types—are not well characterized. HPV genotype-specific incidence of high-grade cervical intraepithelial neoplasia or more severe (CIN2+) following an abnormal screening result was examined. Methods: We assessed a US-based prospective, multiracial, clinical cohort of 343 colposcopy patients with normal histology (n = 226) or CIN1 (n = 117). Baseline cervical samples underwent HPV DNA genotyping, and participants were followed up to 5 years. Genotype-specific CIN2+ incidence rates (IR) were estimated with accelerated failure time models. Five-year CIN2+ risks were estimated nonparametrically for hierarchical hrHPV risk groups (HPV16; else HPV18/45; else HPV31/33/35/52/58; else HPV39/51/56/59/68). Results: At enrollment, median participant age was 30.1 years; most (63%) were hrHPV-positive. Over follow-up, 24 participants progressed to CIN2+ (7.0%). CIN2+ IR among hrHPV-positive participants was 3.4/1,000 person-months. CIN2+ IRs were highest for HPV16 (8.3), HPV33 (7.8), and HPV58 (4.9). Five-year CIN2+ risk was higher for HPV16 (0.34) compared with HPV18/45 (0.12), HPV31/33/35/52/58 (0.12), and HPV39/51/56/59/68 (0.16) (P = 0.05). Conclusions: Non-16/18 hrHPV types are associated with differential CIN2+ progression rates. HPV16, 33, and 58 exhibited the highest rates over 5 years. HPV risk groups warrant further investigation in diverse US populations. Impact: These novel data assessing extended HPV genotyping in a diverse clinical cohort can inform future directions to improve screening practices in the general population.
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Extended genotyping to determine whom to treat based on risk has been shown to improve sensitivity for the detection of CIN 3+ and facilitate safe deferring of colposcopy if the HPV types are of lower carcinogenic potential (Group d).
“Extended genotyping (inclusion of the next most carcinogenic types - Group 1c) to determine whom to treat based on risk has also been shown to improve sensitivity for the detection of CIN 3+ and facilitate safe deferring of colposcopy if the HPV types are of lower carcinogenic potential (Group d).51 52”
From Protocol for a cervical screening implementation trial comparing two approaches for delivering HPV self-collection in low-resource settings in India: a type 3 hybrid cluster randomised controlled trial (SHE-CAN) (2025) · cites this paper as [51]
The Discussion (page unavailable) supports the potential use of extended genotyping to distinguish progression risks and guide more conservative management. But this study assessed CIN2+ risk in patients already referred for colposcopy, not improved sensitivity for detecting CIN3+ or the safety of deferring colposcopy. Its Results also report that the lowest-risk genotype group had a five-year CIN2+ risk similar to the intermediate groups. (LLM, conf=0.90)
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Metadata
- Authors
- Bukowski, A., Hoyo, C., Hudgens, M. G., Brewster, W. R., Valea, F., Bentley, R. C., Vidal, A. C., Maguire, R. L., Schmitt, J. W., Murphy, S. K., North, K. E., & Smith, J. S.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- North Carolina State University (US)
- Carilion Clinic (US)
- Duke University (US)
- Cedars-Sinai Medical Center (US)
- Corresponding author
- Smith, Jennifer S.
- ORCID
- Venue
- Cancer Epidemiology, Biomarkers & Prevention
- Published
- 2022-06-02
- Volume
- 31
- Issue
- 8
- Pages
- 1564-1571
- ISSN
- 1055-9965 (ISSN-L)
- 1538-7755
- PMC
- PMC9350926
- OpenAlex
- W4281964475
- Cited by
- 9
- References
- 39
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 4
- FWCI
- 1.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Epidemiology Biomarkers & Prevention (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- NIH NCI (F30CA257181, T32 5T32CA57726-29, R01CA142983, R01CA142983-02S1)
- Topics
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Women's cancer prevention and management
- Keywords
- HPV genotyping, high-risk HPV, cervical intraepithelial neoplasia, HPV16, HPV 33, HPV58, cervical cancer screening, colposcopy
- MeSH terms
- Adult, Uterine Cervical Neoplasms, Female, Genotype, Humans, Prospective Studies, Papillomaviridae, Papillomavirus Infections, Human papillomavirus 18, Human papillomavirus 16, Early Detection of Cancer
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