Journal
CANCER
Volume 127, Issue 6, Pages 850-864Publisher
WILEY
DOI: 10.1002/cncr.33221
Keywords
anal cancer; biomarker; blood biomarker; cancer prevention; cancer surveillance; cervical cancer; human papillomavirus (HPV); oropharyngeal cancer; penile cancer; screening
Categories
Funding
- Simmons Comprehensive Cancer Center Biomarker Research Core Pilot Award
- Simmons Comprehensive Cancer Center Translational Research Pilot Grant
- Eugene P. Frenkel, MD, Endowed Scholarship in Clinical Medicine [1UM1CA221940-01]
- National Cancer Institute [1UM1CA221940-01]
- National Institutes of Health [P30 CA016672]
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This study found that HPV-16 E6 antibodies and circulating HPV-16 DNA are the most representative and promising blood-based biomarkers for HPV-associated cancers. Comparative validity analyses are needed, and further research on biomarkers targeting more high-risk HPV types is warranted.
Background Despite the significant societal burden of human papillomavirus (HPV)-associated cancers, clinical screening interventions for HPV-associated noncervical cancers are not available. Blood-based biomarkers may help close this gap in care. Methods 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-text review. Eligibility criteria included the assessment of a blood-based biomarker within a cohort or case-control study. Results One hundred thirty-seven studies were included. Among all biomarkers assessed, HPV-16 E seropositivity and circulating HPV DNA were most significantly correlated with HPV-associated cancers in comparison with cancer-free controls. In most scenarios, HPV-16 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], 59.40-298.21; cOR for HPV-unspecified OPC, 25.41; 95% CI, 8.71-74.06; cOR for prediagnostic HPV-unspecified OPC, 59.00; 95% CI, 15.39-226.25; cOR for HPV-unspecified cervical cancer, 12.05; 95% CI, 3.23-44.97; cOR for HPV-unspecified anal cancer, 73.60; 95% CI, 19.68-275.33; cOR for HPV-unspecified penile cancer, 16.25; 95% CI, 2.83-93.48). Circulating HPV-16 DNA was a valid biomarker for cervical cancer (cOR, 15.72; 95% CI, 3.41-72.57). In 3 cervical cancer case-control studies, cases exhibited unique microRNA expression profiles in comparison with controls. Other assessed biomarker candidates were not valid. Conclusions HPV-16 E6 antibodies and circulating HPV-16 DNA are the most robustly analyzed and most promising blood-based biomarkers for HPV-associated cancers to date. Comparative validity analyses are warranted. Variations in tumor type-specific, high-risk HPV DNA prevalence according to anatomic site and world region highlight the need for biomarkers targeting more high-risk HPV types. Further investigation of blood-based microRNA expression profiling appears indicated.
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