Dataset Information

Blood-based biomarkers of human papillomavirus-associated cancers: A systematic review and meta-analysis.

ABSTRACT:

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.

SUBMITTER: Balachandra S

PROVIDER: S-EPMC8135101 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Blood-based biomarkers of human papillomavirus-associated cancers: A systematic review and meta-analysis.

Balachandra Sanjana S Kusin Samuel B SB Lee Rebecca R Blackwell James-Michael JM Tiro Jasmin A JA Cowell Lindsay G LG Chiang Cheng-Ming CM Wu Shwu-Yuan SY Varma Sanskriti S Rivera Erika L EL Mayo Helen G HG Ding Lianghao L Sumer Baran D BD Lea Jayanthi S JS Bagrodia Aditya A Farkas Linda M LM Wang Richard R Fakhry Carole C Dahlstrom Kristina R KR Sturgis Erich M EM Day Andrew T AT

Cancer 20201203 6

<h4>Background</h4>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.<h4>Methods</h4>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 as ...[more]

PMID: 33270909

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Project description:Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate below 5%. Carbohydrate antigen 19-9 (CA19-9) is the most commonly used blood-based biomarker for PDAC in current clinical practice, despite having been shown repeatedly to be inaccurate and have poor diagnostic performance. This review aims to assess the reported diagnostic accuracy of all blood-based biomarkers investigated to date in PDAC, by directly comparing individual biomarkers and multi-biomarker panels, both containing CA19-9 and not (novel). A systematic review was conducted in accordance with PRISMA standards in July 2020. Individualized search strategies for three academic databases identified 5,885 studies between the years 1973 and 2020. After two rounds of screening, 250 studies were included. Data were extracted and assessed for bias. A multivariate three-level meta-analysis with subgroup moderators was run in R using AUC values as effect size. On the basis of this model, the pooled AUC value for all multi-biomarker panels (AUC = 0.898; 95% confidence interval (CI): 0.88-0.91) was significantly higher than all single biomarkers (AUC = 0.803; 95% CI: 0.78-0.83; P < 0.0001). The pooled AUC value for CA19-9 alone was significantly lower compared with the multi-biomarker panels containing CA19-9 (P < 0.0001). For the novel biomarkers, the pooled AUC for single biomarkers was also significantly lower compared with multi-biomarker panels (P < 0.0001). Novel biomarkers that have been repeatedly examined across the literature, such as TIMP-1, CEA, and CA125, are highlighted as promising. These results suggest that CA19-9 may be best used as an addition to a panel of biomarkers rather than alone, and that multi-biomarker panels generate the most robust results in blood-based PDAC diagnosis.SignificanceIn a systematic review and three-level multivariate meta-analysis, it is shown for the first time that blood-based multi-biomarker panels for the diagnosis of PDAC exhibit superior performance in comparison with single biomarkers. CA19-9 is demonstrated to have limited utility alone, and to perform poorly in patient control cohorts of both healthy and benign individuals. Multi-biomarker panels containing CA19-9 produce the best diagnostic performance overall.

Project description:ImportanceAlthough the survival impact of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OPSCC) is well known, there has been conflicting and scarce evidence on the role of HPV in non-OPSCC.ObjectiveTo undertake a Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-compliant systematic review and meta-analysis of all published studies on the association between HPV status and survival outcomes in patients with non-OPSCC, analyzing each site separately.Data sourcesPubMed, CINAHL, and Embase were searched from 1946 to December 16, 2019, for English-language articles.Study selectionAnalysis comprised randomized clinical trials or observational studies that each included at least 10 patients with non-OPSCC in which the presence of HPV was analyzed, survival outcomes were reported, and a clinical follow-up of 1 year or more was performed. Studies excluded were those in which data on OPSCC and non-OPSCC were not distinguished between both cohorts and studies on patients with distant metastatic tumors at diagnosis. Final analysis included outcomes that were analyzed in at least 3 studies.Data extraction and synthesisTwo reviewers independently abstracted the data. Risk of bias was estimated with the Newcastle-Ottawa Scale. Meta-analysis was performed using the random-effects model.Main outcomes and measuresThe primary end point was overall survival (OS); secondary end points were disease-specific survival (DSS) and disease-free survival (DFS).ResultsOf the 3947 articles screened, a total of 22 observational and 2 randomized clinical trials were included in the analysis, representing 24 854 patients. In oral cavity locations, OS was not significantly associated with HPV positivity (hazard ratio [HR], 1.16; 95% CI, 0.83-1.61; I2 = 71%); however, HPV-positive tumors showed worse DFS (HR, 1.81; 95% CI, 1.12-2.91; I2 = 47%). Laryngeal and hypopharyngeal HPV-positive tumors were associated with improved OS (HR, 0.71; 95% CI, 0.54-0.92; I2 = 38% and HR, 0.60; 95% CI, 0.47-0.76; I2 = 0%), respectively, whereas, in nasopharyngeal locations HPV was not associated with OS (HR, 0.82; 95% CI, 0.49-1.38; I2 = 46%) or DSS (HR, 0.55; 95% CI, 0.22-1.42; I2 = 65%).Conclusions and relevanceIn this meta-analysis of 24 studies, HPV was associated with improved OS in laryngeal and hypopharyngeal locations but not in the oral cavity and the nasopharynx. This information may be useful for future clinical studies of laryngeal and hypopharyngeal tumors and whether HPV status should be incorporated in prognostication of patients with these cancers.

Dataset Information

Blood-based biomarkers of human papillomavirus-associated cancers: A systematic review and meta-analysis.

Background

Methods

Results

Conclusions

Publications

Blood-based biomarkers of human papillomavirus-associated cancers: A systematic review and meta-analysis.

Similar Datasets

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