Table 1.
Overview of included studies.
| Author (Year of Publication) Country [Study] | Study Period | OPSCC Patients. Total/HPV+ | Sample | Method of Testing | Reference | True Positive | False Positive | False Negative | True Negative | Results |
|---|---|---|---|---|---|---|---|---|---|---|
| Henley-Smith et al. (2020) London [21] | 2005–2016 | 100/38 | FFPE | RNA ISH | p16 IHC, staining >70% and DNA ISH | 38 | 18 | 0 | 44 | NR. The 18 false positive cases were p16+/HPV- |
| Shengming et al. (2020) China [22] | 2014–2019 | 257/47 | FFPE | p16 IHC staining >70% DNA PCR |
RNA ISH | p16: 44 DNA PCR: 47 p16/DNA PCR: 44 |
p16: 22 DNA PCR: 4 p16/DNA PCR: 4 |
p16: 3 DNA PCR: 0 p16/DNA PCR: 3 |
p16: 188 DNA PCR: 206 p16/DNA PCR: 206 |
p16 ISH: Sen: 93.6%; Spe: 89.10% DNA PCR: Sen: 97.9%; Spe: 97.6% p16 and DNA PCR: Sen: 91.7%; Spe: 98.1% |
| Mes et al. (2019) Netherlands [23] | 2008–2011 | 80/20 | FFPE | DNA RT-PCR | HPV16 E6 mRNA RT-PCR | 19 | 0 | 1 | 55 | NR |
| Randén-Brady et al. (2019) Finland [24] | Study I: 2000–2009 Study 2: 2012–2016 |
Study 1: 202/NR Study 2: 155/NR Study 1 + 2: HPV positive: 226 |
FFPE | Study 1: DNA ISH Study 2: DNA PCR Study 1 + 2: results combined: E6/E7 mRNA ISH |
p16 IHC, staining >70% | mRNA: 211 DNA ISH: 101 DNA PCR: 91 |
mRNA: 10 DNA ISH: 4 HPV PCR: 5 |
mRNA: 15 DNA ISH: 16 HPV PCR: 18 |
mRNA: 121 DNA ISH: 81 HPV PCR: 41 |
mRNA ISH: Sen: 93.4%; Spe: 92.4% DNA ISH: Sen: 86.3%; Spe: 95.3% DNA PCR: Sen: 83.5%; Spe: 89.1% |
| Craig et al. (2019) Ireland [25] | 2000–2011 | 221/90 | FFPE | RNA-ISH DNA-ISH DNA-PCR |
p16 IHC, staining >70% | DNA PCR: 71 DNA ISH: 67 RNA ISH:80 |
DNA PCR: 43 DNA ISH: 0 RNA ISH: 0 |
DNA PCR: 19 DNA ISH: 23 RNA ISH:10 |
DNA PCR: 88 DNA ISH: 131 RNA ISH: 131 |
DNA PCR: Sen: 79% (95% CI: 69–87); Spe: 67% (95% CI: 58–75) DNA ISH: Sen: 74% (95% CI: 64–83); Spe: 100% (95% CI: 87–100) RNA ISH: Sen: 88% (95% CI: 80–94); Spe: 100% (95% CI: 96–100) |
| Mena et al. (2018) Spain [26] | 1990–2013 | 788/80 | FFPE | DNA PCR p16 IHC, staining >70% |
E6 mRNA RT-PCR | DNA PCR/p16: 58 p16: 58 |
DNA PCR/p16: 0 p16: 28 |
DNA PCR/p16: 9 p16: 9 |
DNA PCR/p16: 721 p16: 691 |
DNA PCR/p16: Sen: 86.6% (95% CI 76.0–93.7); Spe: 100.0% (95% CI 99.5–100.0). p16: Sen: 86.6% (95% CI 76.0–93.7); Spe: 96.1% (95% CI 94.4–97.4) |
| Meng et al. (2018) China [27] | 2000–2016 | 1470/81 | FFPE | DNA PCR | p16 IHC, staining >80% | 78 | 0 | 3 | 1389 | Sen: 100% Spe: 96% |
| Augustin et al. (2018) France [28] | 2011–2013 | 126/56 | FFPE | p16 IHC, staining >70% DNA-ISH RNA-ISH |
DNA PCR | p16: 46 DNA ISH: 41 RNA ISH:49 |
p16: 7 DNA ISH: 2 RNA ISH: 2 |
p16: 10 DNA ISH: 15 RNA ISH: 7 |
p16: 68 DNA ISH: 63 RNA ISH: 68 |
p16: Sen: 82% (95% CI 70–91); Spe: 90% (95% CI 80–96) DNA ISH: Sen: 73% (95% CI 60–84); Spe: 97% (95% CI 90–100) RNA ISH: Sen: 88% (95% CI 76–95); Spe: 97% (95% CI 90–100) p16 and DNA ISH: Sen: 88% (95% CI 76–95); Spe: 97% (95% CI 90–100) p16 and RNA ISH: Sen: 95% (95% CI 85–99); Spe: 100% (95% CI 92–100) |
| Mendez-Pena et al. (2017) Boston, USA [29] | 2015–2016 | 57/26 | FFPE | RNA ISH DNA ISH p16 IHC, staining >50% |
DNA PCR | RNA ISH: 26 DNA ISH: 23 p16: 24 |
RNA ISH: 4 DNA ISH: 8 p16: 13 |
RNA ISH: 0 DNA ISH: 3 p16: 1 |
RNA ISH: 27 DNA ISH: 23 p16: 16 |
RNA ISH: Sen: 100%; Spe: 87% DNA ISH: Sen: 88%; Spe: 74% p16: Sen: 96%; Spe: 55% |
| Wright et al. (2020) Tennessee, USA [30] | NR | 20/19 | FNA | DNA RT-PCR | p16 IHC, staining >70% | 19 | 0 | 0 | 1 | Sen: 100%; Spe: 100% |
| Menegaldo et al. (2020) Italy [31] | 2016–2019 | 29/16 | FNA | HPV16 and HPV18 E6 oncoproteins, lateral flow immunochromatographic strip test | p16 IHC, staining >70% combined with DNA PCR and/or E6 seropositivity | 15 | 0 | 1 | 11 | Sen: 94% (95% CI: 70–100); Spe: 100% (95% CI: 72–100) |
| Channir (2016) Denmark [32] | 2002–2016 | 71/71 (HPV- group: 47/7 with OSCC, 20 Warthin’s tumour, 20 branchial cleft cyst) |
FNA | DNA PCR p16 IHC, staining <75% |
DNA PCR | 68 | 0 | 3 | 47 | Sen: NR. Spe: 100% (95% CI 92.5–100.0) |
| Sivars et al. (2016) Sweden [33] | 2013–2016 | 16/13 | FNA | DNA multiplex assay | p16 IHC, staining >70% | 13 | 0 | 0 | 3 | Sen: 100%; Spe: 100% |
| Chernesky et al. (2018) Canada [34] | NR | 59/48 | Saliva and oral swabs (BOT and tonsillar area) pooled and FNA | (1) OncoE6 proteins–lateral flow strip (2) HPV E6/E7 mRNA assay (3) DNA PCR |
p16 IHC, staining >70% | Oral sample: (1) 3 (2) 22 (3) 35 FNA: (1) 38 (2) 46 (3) 42 |
Oral sample: (1) 0 (2) 0 (3) 1 FNA: (1) 1 (2) 1 (3) 2 |
Oral sample: (1) 45 (2) 26 (3) 11 FNA: (1) 10 (2) 2 (3) 2 |
Oral sample: (1) 11 (2) 11 (3) 10 FNA: (1) 10 (2) 10 (3) 9 |
NR |
| Borena et al. (2020) Austria [35] | 2018–2020 | 50/23 | Cytology brush tests of tumour surface | E7 antigen test, ELISA | p16 IHC, staining >66% and DNA PCR | 14 | 9 | 9 | 18 | Sen: 60.9% (95% CI 38.5–80.3); Spe: 66.7% (95% CI 46–83.5) |
| Martin-Gomez et al. (2019) Florida, USA [36] | 2014–2017 | 171/157 | Oral rinse | DNA PCR | p16 IHC, staining >70% and DNA PCR | 119 | 7 | 38 | 7 | Sen: 75.8%; Spe: 50.0% |
| Fakhry et al. (2019) Ohio and Baltimore USA [37] | 2011–2016 | 217/187 | Oral rinse | DNA PCR | mRNA E6 or E7 or p16 IHC/combined with DNA ISH | 161 | 5 | 26 | 25 | NR |
| Qureishi et al. (2018) United Kingdom [38] | 2015–2016 | 46/36 | Oral rinse | DNA PCR | p16 IHC, staining >70% and DNA ISH. Positive if: p16+/no HPV DNA test, p16+/HPV DNA+ or p16- and HPV DNA+. |
p16/HPV: 26 | p16/HPV: 1 | p16/HPV: 10 | p16/HPV: 9 | Oral rinse vs. p16: Sen: 73.5% (95% CI 55.6–87.1); Spe: 83.3% (95% CI 51.6–97.9). Oral rinse vs. DNA ISH: Sen: 66.7% (95% CI 43–85.4); Spe: 87.5% (95% CI 47.4–99.7). Oral rinse vs. p16/HPV: Sen: 72.2 (95% CI 54.8–85.8); Spe: 90 (95% CI 55.5–99.8) |
| Reder et al. (2020) Germany [39] | 2014–2017 | 48/28 | Plasma | E6 and E7 oncogenes RT-PCR | HPV16-DNA RT-PCR | 23 | 0 | 7 | 20 | Sen: 77%; Spe: 100% |
| Economopoulou et al. (2019) Ohio, USA [40] | NR | 22/14 | Blood (CtC) | HPV16 E6/E7 mRNA qPCR | p16 IHC, staining > 70% and HPV DNA qPCR | 3 | 0 | 11 (7 HPV16) | 8 | NR |
| Chera et al. (2019) North Carolina, USA [41] | 2016 –2018 | 103/103. 155 controls (55 healty controls and 60 non-HPV malignancies (not OPSCC)) |
Plasma | DNA, ddPCR | p16 IHC, staining > 70% | 84 | Control: 3 | 19 | Control: 112 | Sen: 89%; Spe: 97% |
| Ren et al. (2019) China [42] | 2007–2017 | 783/611 | Plasma | HPV16 E6 antibody advanced multiplex analysis/ELISA | p16 IHC, staining >70% | 545 | 8 | 66 | 164 | Sen: 89% (95%CI 86–92); Spe: 95% (95%CI 91–98) |
| Damerla et al. New York, USA (2019) [43] | NR | 97/97. (HPV- group: 7 HPV- HNC and 20 healthy controls) |
Plasma | HPV16 and HPV33 ddPCR | p16 IHC, staining >70% or DNA ISH, or RNA ISH | 90 | 0 | 7 | 27 | Sen: 92.8%; Spe: 100% |
| Hanna et al. (2018) Boston, USA [44] | 2017–2018 | 17/15 | Blood (Obtained at any time during treatment) | DNA ddPCR | p16 IHC, staining >70% and DNA ISH or PCR | 14 | 1 | 1 | 1 | Sen: 93.3% (95%CI 68.0–99.8); Spe: 50% (95%CI 1.3–98.7) |
| Kuhs et al. (2017) Pittsburgh, USA [45] | 2003–2013 | 112/87 | Serum | HPV16 E6 multiplex serology | p16 IHC, staining >70% and DNA ISH | 78 | 1 | 9 | 24 | Sen: 89.7% (95%CI, 81.3–95.2); Spe: 96.0% (95% CI, 79.6–99.9) |
| Holzinger et al. (2017) Germany and Italy [46] | NR | 120/66 | Serum | HPV16 E6 antibody ELISA | HPV16 DNA, RT-PCR | 63 | 1 | 3 | 53 | Sen: 96% (95%CI 88–98); Spe: 98% (95%CI 90–100) |
| Mazurek et al. (2016) Poland [47] | 2011–2013 | 51/29 | Plasma | HPV16 DNA, RT-PCR | HPV16 DNA qPCR | 21 | 0 | 8 | 22 | Sen: 72%; Spe: 100%. |
Abbreviation: Oropharyngeal squamous cell carcinoma (OPSCC); Human Papillomavirus (HPV); 95% confidence intervals (95% CI); Immunohistochemistry (IHC); In situ hybridization (ISH); Droplet-based digital PCR (ddPCR); Reverse transcriptase polymerase chain reaction (RT-PCR); Not reported (NR); Sensitivity (sen); Specificity (SPE); Unstimulated whole mouth saliva (UWMS); Formalin-fixed paraffin-embedded (FFPE); Fine needle aspiration (FNA); Base of tongue (BOT); Circulating tumour cells (CtC).