Non-Cochrane · DTA · PM42211773
Diagnostic accuracy of HPV DNA in oral gargle and rinse samples for Head and neck squamous cell carcinoma: A systematic review and meta-analysis.
Wijaya Arbi, Soedarsono Nurtami, Julia Vera, et al. · The Japanese dental science review · 2026 · PubMed · doi:10.1016/j.jdsr.2026.05.001
Findings
Population Adults with histologically confirmed HNSCC and healthy controls
51 findings
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled sensitivity Cancer target: HNSCC (mixed subsites) | Sensitivity 0.611 [0.327, 0.835] GRADE not reported 6 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Diagnostic odds ratio Gargle/rinse duration: < 30 s | DOR 26.66 [12.45, 57.11] GRADE not reported 3 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled specificity Study design: Cross-sectional | Specificity 0.819 [0.641, 0.92] GRADE not reported 6 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Area under the SROC curve | AUC 0.91 [0.88, 0.93] GRADE not reported 10 studies · 1315 participants |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Diagnostic odds ratio Gargle/rinse duration: >= 30 s | DOR 14.66 [7.80, 27.52] GRADE not reported 12 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled sensitivity Study design: Case control | Sensitivity 0.639 [0.526, 0.738] GRADE not reported 3 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled sensitivity Gargle/rinse duration: >= 30 s | Sensitivity 0.65 [0.554, 0.735] GRADE not reported 12 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Diagnostic odds ratio Sample type: Oral gargle | DOR 16.66 [8.52, 32.62] GRADE not reported 8 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Diagnostic odds ratio Sample type: Oral rinse | DOR 16.73 [5.83, 47.94] GRADE not reported 7 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Negative likelihood ratio | LR- 0.32 GRADE not reported 10 studies · 1315 participants |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Diagnostic odds ratio Detection method: SPF10-based | DOR 11.07 [6.75, 18.16] GRADE not reported 9 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled specificity Cancer target: HNSCC (mixed subsites) | Specificity 0.89 [0.829, 0.931] GRADE not reported 6 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled sensitivity Study design: Prospective | Sensitivity 0.564 [0.347, 0.759] GRADE not reported 6 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Diagnostic odds ratio Collection volume: >= 15 mL | DOR 10.00 [5.56, 18.01] GRADE not reported 10 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled specificity Collection volume: >= 15 mL | Specificity 0.856 [0.767, 0.915] GRADE not reported 10 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled specificity Cancer target: OPSCC | Specificity 0.885 [0.8, 0.937] GRADE not reported 9 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Diagnostic odds ratio Study design: Case control | DOR 19.26 [11.19, 33.15] GRADE not reported 3 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled specificity Detection method: SPF10-based | Specificity 0.874 [0.795, 0.926] GRADE not reported 9 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Diagnostic odds ratio Study design: Prospective | DOR 13.80 [5.14, 37.08] GRADE not reported 6 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled sensitivity Detection method: SPF10-based | Sensitivity 0.609 [0.516, 0.695] GRADE not reported 9 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled specificity Gargle/rinse duration: < 30 s | Specificity 0.901 [0.829, 0.944] GRADE not reported 3 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled specificity Collection volume: <= 10 mL | Specificity 0.918 [0.854, 0.955] GRADE not reported 3 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled specificity HPV type: pan-HPV/multi-type | Specificity 0.879 [0.806, 0.927] GRADE not reported 11 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Diagnostic odds ratio Cancer target: OPSCC | DOR 17.78 [9.73, 32.46] GRADE not reported 9 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled specificity Study design: Prospective | Specificity 0.899 [0.846, 0.936] GRADE not reported 6 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled sensitivity Sample type: Oral rinse | Sensitivity 0.611 [0.382, 0.799] GRADE not reported 7 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Diagnostic odds ratio HPV type: pan-HPV/multi-type | DOR 11.85 [7.17, 19.57] GRADE not reported 11 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled sensitivity Cancer target: OPSCC | Sensitivity 0.71 [0.638, 0.772] GRADE not reported 9 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled sensitivity Detection method: non-SPF10 | Sensitivity 0.821 [0.706, 0.897] GRADE not reported 6 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled specificity Study design: Case control | Specificity 0.917 [0.832, 0.961] GRADE not reported 3 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Diagnostic odds ratio Cancer target: HNSCC (mixed subsites) | DOR 15.61 [4.32, 56.43] GRADE not reported 6 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled sensitivity Gargle/rinse duration: < 30 s | Sensitivity 0.756 [0.577, 0.875] GRADE not reported 3 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled sensitivity HPV type: pan-HPV/multi-type | Sensitivity 0.625 [0.532, 0.709] GRADE not reported 11 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Diagnostic odds ratio | lnDOR 2.71 [2.16, 3.25] GRADE not reported 10 studies · 1315 participants |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled specificity HPV type: HPV16-specific | Specificity 0.911 [0.855, 0.946] GRADE not reported 4 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Diagnostic odds ratio Study design: Cross-sectional | DOR 25.43 [5.70, 113.52] GRADE not reported 6 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Diagnostic odds ratio HPV type: HPV16-specific | DOR 115.58 [17.01, 784.46] GRADE not reported 4 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled sensitivity Study design: Cross-sectional | Sensitivity 0.765 [0.674, 0.837] GRADE not reported 6 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Positive likelihood ratio | LR+ 8.0 GRADE not reported 10 studies · 1315 participants |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled specificity Sample type: Oral rinse | Specificity 0.899 [0.852, 0.933] GRADE not reported 7 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled sensitivity Collection volume: >= 15 mL | Sensitivity 0.631 [0.52, 0.73] GRADE not reported 10 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled specificity | Specificity 0.91 [0.88, 0.95] GRADE not reported 10 studies · 1315 participants |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled sensitivity | Sensitivity 0.68 [0.58, 0.79] GRADE not reported 10 studies · 1315 participants |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled specificity Detection method: non-SPF10 | Specificity 0.912 [0.853, 0.949] GRADE not reported 6 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled specificity Gargle/rinse duration: >= 30 s | Specificity 0.888 [0.823, 0.931] GRADE not reported 12 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Diagnostic odds ratio Collection volume: <= 10 mL | DOR 143.88 [17.73, 1169.11] GRADE not reported 3 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled sensitivity Sample type: Oral gargle | Sensitivity 0.706 [0.624, 0.776] GRADE not reported 8 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Diagnostic odds ratio Detection method: non-SPF10 | DOR 68.44 [26.10, 179.47] GRADE not reported 6 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled sensitivity Collection volume: <= 10 mL | Sensitivity 0.846 [0.687, 0.932] GRADE not reported 3 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled specificity Sample type: Oral gargle | Specificity 0.873 [0.767, 0.935] GRADE not reported 8 studies |
| HPV DNA detection in oral gargle or oral rinse samples (index test) | Histopathological diagnosis of HNSCC (reference standard) | Pooled sensitivity HPV type: HPV16-specific | Sensitivity 0.854 [0.667, 0.945] GRADE not reported 4 studies |
Included primary studies 10
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Chai 2016 A pilot study to compare the detection of HPV-16 biomarkers in salivary oral rinses with tumour p16(INK4a) expression in head and neck… PMID:26940728 | 2016 | this review only | not stated | not extracted yet |
| Dickey 2022 Methylation of HPV16 and EPB41L3 in oral gargles and the detection of early and late oropharyngeal cancer. PMID:35619332 | 2022 | this review only | not stated | not extracted yet |
| Galati 2025 HPV Biomarkers in Oral and Blood-Derived Body Fluids in Head and Neck Cancer Patients. PMID:40052199 | 2025 | this review only | not stated | not extracted yet |
| Giuliano 2020 Methylation of HPV 16 and EPB41L3 in oral gargles: Associations with oropharyngeal cancer detection and tumor characteristics. PMID:31304592 | 2020 | this review only | not stated | not extracted yet |
| Imai 2016 Human papilloma virus detection in oropharyngeal cancer with gargle samples. PMID:29709129 | 2016 | this review only | not stated | not extracted yet |
| Loermann 2022 High-Risk Human Papillomavirus (HR-HPV) DNA Detection in Mouthwashes for Diagnosis of HPV-Driven Oropharynx Cancer and Its Curative… PMID:36233378 | 2022 | this review only | not stated | not extracted yet |
| Martin-Gomez 2019 Oral gargle-tumor biopsy human papillomavirus (HPV) agreement and associated factors among oropharyngeal squamous cell carcinoma (OPSCC)… PMID:31010629 | 2019 | this review only | not stated | not extracted yet |
| Rosenthal 2017 Detection of HPV related oropharyngeal cancer in oral rinse specimens. PMID:29312616 | 2017 | this review only | not stated | not extracted yet |
| Tanaka 2022 Performance of oral HPV DNA, oral HPV mRNA and circulating tumor HPV DNA in the detection of HPV-related oropharyngeal cancer and cancer… PMID:34486724 | 2022 | this review only | not stated | not extracted yet |
| Yoshida 2017 Usefulness of human papillomavirus detection in oral rinse as a biomarker of oropharyngeal cancer. PMID:28093931 | 2017 | this review only | not stated | not extracted yet |
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Adults (>=18 years) with histologically confirmed HNSCC at any subsite and healthy controls | 1315 participants (HNSCC cases and controls) in 10 studies (15 datasets); mostly OPSCC (n=6 studies) |
| Intervention | Index test: oral HPV-related DNA-based assays (HPV DNA detection, HPV DNA methylation) on oral gargle or oral rinse samples | HPV DNA in oral gargle (8 datasets) or oral rinse (7 datasets); SPF10-based (9) and non-SPF10 (6) assays |
| Comparison | Reference standard: histopathological diagnosis of HNSCC, with or without tissue HPV/p16 confirmation (p16 IHC, HPV ISH, E6/E7 mRNA) | Histopathology with p16 IHC and/or tissue HPV testing (10 studies) |
| Outcomes | Sensitivity, specificity, DOR, SROC AUC, likelihood ratios (2x2 data: TP, FP, TN, FN) | Pooled sensitivity 0.68; specificity 0.91; AUC 0.91; lnDOR 2.71; LR+ 8.0; LR- 0.32 |
| Study designs | Prospective, retrospective and cross-sectional cohort studies and case-control studies | Cross-sectional (n=5), prospective cohort (n=3), case-control (n=2) |
| Timing | Not specified | Not specified |