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Co\u2010occurrence of hrHPV infections is common and complicates carcinogenicity assessment; accurate attribution requires tissue\u2010based 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\u2010based genotyping, including whole tissue sections (WTS) and laser\u2010capture 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\u2010type 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\u2010one 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\u2010specific risk assessment in screening and management.<\/jats:p>","DOI":"10.1002\/ijc.32919","type":"journal-article","created":{"date-parts":[[2020,2,10]],"date-time":"2020-02-10T07:29:11Z","timestamp":1581319751000},"page":"2836-2844","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Identification of HPV genotypes causing cervical precancer using tissue\u2010based genotyping"],"prefix":"10.1002","volume":"146","author":[{"given":"Rebecca","family":"Venetianer","sequence":"first","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics National Cancer Institute, National Institutes of Health  Rockville MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0435-7376","authenticated-orcid":false,"given":"Megan 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