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Blood\u2010based biomarkers may help close this gap in care.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Five databases were searched, 5687 articles were identified, and 3631 unique candidate titles and abstracts were independently reviewed by 2 authors; 702 articles underwent a full\u2010text review. Eligibility criteria included the assessment of a blood\u2010based biomarker within a cohort or case\u2010control study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>One hundred thirty\u2010seven studies were included. Among all biomarkers assessed, HPV\u201016 E seropositivity and circulating HPV DNA were most significantly correlated with HPV\u2010associated cancers in comparison with cancer\u2010free controls. In most scenarios, HPV\u201016 E6 seropositivity varied nonsignificantly according to tumor type, specimen collection timing, and anatomic site (crude odds ratio [cOR] for p16+ or HPV+ oropharyngeal cancer [OPC], 133.10; 95% confidence interval [CI], 59.40\u2010298.21; cOR for HPV\u2010unspecified OPC, 25.41; 95% CI, 8.71\u201074.06; cOR for prediagnostic HPV\u2010unspecified OPC, 59.00; 95% CI, 15.39\u2010226.25; cOR for HPV\u2010unspecified cervical cancer, 12.05; 95% CI, 3.23\u201044.97; cOR for HPV\u2010unspecified anal cancer, 73.60; 95% CI, 19.68\u2010275.33; cOR for HPV\u2010unspecified penile cancer, 16.25; 95% CI, 2.83\u201093.48). Circulating HPV\u201016 DNA was a valid biomarker for cervical cancer (cOR, 15.72; 95% CI, 3.41\u201072.57). In 3 cervical cancer case\u2010control studies, cases exhibited unique microRNA expression profiles in comparison with controls. Other assessed biomarker candidates were not valid.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>HPV\u201016 E6 antibodies and circulating HPV\u201016 DNA are the most robustly analyzed and most promising blood\u2010based biomarkers for HPV\u2010associated cancers to date. Comparative validity analyses are warranted. Variations in tumor type\u2013specific, high\u2010risk HPV DNA prevalence according to anatomic site and world region highlight the need for biomarkers targeting more high\u2010risk HPV types. Further investigation of blood\u2010based microRNA expression profiling appears indicated.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.33221","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T12:30:54Z","timestamp":1606998654000},"page":"850-864","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Blood\u2010based biomarkers of human papillomavirus\u2013associated cancers: A systematic review and meta\u2010analysis"],"prefix":"10.1002","volume":"127","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9887-3525","authenticated-orcid":false,"given":"Sanjana","family":"Balachandra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel 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