We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Identification of HPV genotypes causing cervical precancer using tissue‐based genotyping.
- Authors
Venetianer, Rebecca; Clarke, Megan A.; Marel, Jacolien; Tota, Joseph; Schiffman, Mark; Dunn, Samuel Terence; Walker, Joan; Zuna, Rosemary; Quint, Wim; Wentzensen, Nicolas
- Abstract
Identification of high‐risk human papillomavirus genotypes causing cervical precancer is crucial for informing HPV vaccine development and efficacy studies, and for determining which types to include in next‐generation genotyping assays. Co‐occurrence of hrHPV infections is common and complicates carcinogenicity assessment; accurate attribution requires tissue‐based genotyping of precancers. We included all women with cervical intraepithelial neoplasia Grade 2 or worse (CIN2+) from the Biopsy Study, an observational study of 690 women enrolled between 2009 and 2012 at the University of Oklahoma. Tissue‐based genotyping, including whole tissue sections (WTS) and laser‐capture microdissection (LCM), was performed on all precancers with multiple hrHPV infections detected in cytology, totaling over 1,800 HPV genotyping assays. Genotype attribution was compared to hierarchical and proportional hrHPV‐type attribution models. Of 276 women with CIN2+, 122 (44.2%) had multiple hrHPV genotypes in cytology. Of 114 women with genotyping data, 94 had one or more hrHPV detected in tissue. Seventy‐one women (75.5%) had a single causal hrHPV genotype, while 23 women had multiple hrHPV genotypes causing CIN2+. Ten women had multiple causal infections in a single biopsy, contrary to the previous notion that each lesion is caused by a single type only. While HPV16 was the predominant causal hrHPV genotype using all approaches, the hierarchical model overattributed HPV16, whereas other causal hrHPV genotypes, particularly HPV18 and HPV35, were underattributed. Understanding true causal genotypes is important for the evaluation of vaccine efficacy, to estimate the extent of unmasking, and for type‐specific risk assessment in screening and management. What's new?: For cervical cancer vaccine development and efficacy assessment, it's critical to correctly identify the causal strains of HPV. Tissue‐based genotyping is complex and expensive, so attribution models are employed. The hierarchical model attributes the most prevalent genotype to the case, while the proportional model attributes all the genotypes in proportion to their prevalence. Here, the authors performed tissue‐based genotyping on multiple biopsies to determine the true HPV genotype in cervical precancers, and compared the result to attribution models. They found that the hierarchical model overattributes HPV16, and under‐attributes the contribution of HPV18 and HPV35.
- Subjects
CERVICAL intraepithelial neoplasia; UNIVERSITY of Oklahoma; GENOTYPES; PRECANCEROUS conditions; CANCER vaccines; VACCINE effectiveness; PAPILLOMAVIRUSES
- Publication
International Journal of Cancer, 2020, Vol 146, Issue 10, p2836
- ISSN
0020-7136
- Publication type
Article
- DOI
10.1002/ijc.32919