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- Title
Accuracy of Salivary Circulating Tumor Human Papillomavirus DNA in Detecting Oropharyngeal Cancer: A Systematic Review and Meta-Analysis.
- Authors
Lakshmipathy, Deepak; Prasad, Aman; Fritz, Christian G.; Go, Beatrice C.; Rajasekaran, Karthik
- Abstract
Key Points: Question: How accurate is salivary circulating tumor human papillomavirus DNA (ctHPV DNA) in detecting HPV-related oropharyngeal (OP) cancer? Findings: In this bivariate random effects meta-analysis, 6 articles with moderate heterogeneity comprising 263 patients were included, and pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio values demonstrated the test to be more specific than sensitive. Area under the associated summary receiver operating characteristic curve revealed the test to have acceptable accuracy. Meaning: Salivary ctHPV DNA is an acceptably specific test in detecting HPV-associated OP cancer that would benefit from testing in clinical trials before real-time implementation. This systematic review with meta-analysis examines the accuracy of using salivary circulating tumor human papillomavirus (HPV) DNA to detect HPV-associated oropharyngeal cancer. Importance: Circulating tumor human papillomavirus DNA (ctHPV DNA) has shown potential as a biomarker capable of improving outcomes in patients with HPV-related oropharyngeal (OP) cancer. It can be isolated from plasma or saliva, with the latter offering reduced invasiveness and theoretic reduction of lead time. Objective: To perform a systematic review and meta-analysis on the accuracy of salivary ctHPV DNA for detecting HPV-associated OP cancer. Data Sources: Cochrane Library, Embase, PubMed, and Web of Science databases were searched from inception through October 2023. Study Selection: All patients who underwent salivary ctHPV DNA testing at presentation for possible or diagnosed HPV-related OP cancer were included. Non-English and review publications were excluded. Two authors independently voted on article inclusion with a third resolving conflicting votes. Data Extraction and Synthesis: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines, multiple authors independently abstracted data and assessed bias of included articles. Bivariate random-effects meta-analysis was performed with I2 to assess for study heterogeneity. Main Outcomes and Measures: Sensitivities, specificities, positive likelihood ratios (PLR), negative likelihood ratios (NLR), and diagnostic odds ratios (DOR) with 95% CIs alongside area under the curve (AUC) of a summary receiver operating characteristic (SROC) curve were calculated. The initial analysis took place throughout December 2023. Results: Of 440 initially identified articles, 6 met inclusion criteria and demonstrated moderate heterogeneity (I2 = 36%) with low risk of bias and low applicability concerns. Overall, 263 total patients were included with a median (range) age of 58 (39-86) years, and 228 (87%) were male patients. Per updated prognostic staging criteria, localized tumors (ie, stages 1 or 2) comprised most cancers at 139 (77%), whereas advanced ones (ie, stages 3 or 4) comprised the remaining 41 (23%). Pooled sensitivity, specificity, PLR, NLR, and DOR values were 64% (95% CI, 36%-85%), 89% (95% CI, 46%-99%), 11.70 (95% CI, 0.37-77.00), 1.21 (95% CI, 0.08-7.00), and 139.00 (95% CI, 0.05-837.00), respectively. The AUC of the SROC curve was 0.80. Conclusions and Relevance: This study supports salivary ctHPV DNA as an acceptably specific test in detecting HPV-associated OP cancer that would benefit from testing in clinical trials prior to real-time implementation.
- Publication
JAMA Otolaryngology-Head & Neck Surgery, 2024, Vol 150, Issue 7, p580
- ISSN
2168-6181
- Publication type
Article
- DOI
10.1001/jamaoto.2024.1067