Table 1.
Detailed information and quality assessment of all included studies
| Author (Year) | Location | Study Design | Number of cases | Number of controls | Number of EBV positive cancer tissue | Number of EBV positive control | Type of Breast Cancer | Tumor grade | Tissue type (paraffin-embedded tissue/ frozen tissue) | Detection Method | Detection Marker | Newcastle-Ottawa Scale* |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Aboulkassim et al., 2015 25 | Syria | case control | 108 | 13 | 56 | 8 | invasive breast cancer (84), in situ (24) | N/A | paraffin-embedded tissue | PCR, tissue microarray, IHC | IHC: LMP-1IHC: EBNA-1 | 9 |
| Al Hamad et al., 2020 26 | Jordan | case control | 100 | 50 | 24 | 3 | invasive breast cancer (95) and in situ (5) | Grade I = 12 Grade II = 56Grade III = 32 | Paraffin-embedded tissue | RT-PCR, chromogen ISH | EBNA 2ISH: EBER probe | 7 |
| Antonsson et al., 2012 27 | Australia | case control | 54 | 10 | 5 | 0 | invasive breast cancer (52); mixed (1); DCIS (1) | Grade I = 10 Grade II = 23 Grade III = 20 | Frozen tissue | RT-PCR | EBV assay | 8 |
| Charostad et al., 2021 37 | Iran | case control | 51 | 51 | 6 | 1 | N/A | Early (I/II) = 32Advanced (III/IV) = 19 | Frozen tissue | Nested PCR, RT-qPCR | MiR-218 | 7 |
| Dowran et al., 2019 36 | Iran | case control | 150 | 150 | 0 | 0 | Invasive | Grade I = 35Grade II = 67Grade III = 48 | Paraffin-embedded tissue | PCR | BHFR1 region | 8 |
| El-Naby et al., 201729 | USA | case control | 42 | 42 | 10 | 6 | Invasive | Grade I/II = 28 Grade III = 14 |
Paraffin-embedded tissue | Nested PCR, IHC | EBNA-1, LMP-1 | 5 |
| Mohammadizadeh, et al., 2014 35 | Iran | case control | 80 | 80 | 6 | 0 | Invasive | Grade I = 5 Grade II = 40 Grade III = 32 |
Paraffin-embedded tissue | IHC | LMP-1 | 9 |
| Fessahaye et al., 2017 3 8 | Eritrea | case control | 144 | 63 | 47 | 6 | Invasive | N/A | Paraffin-embedded tissue | PCR, ISH and IHC | EBER LMP-1 | 9 |
| Glenn et al., 2012 28 | Australia | case control | standard PCR: 50, in-situ PCR: 27 | standard PCR: 40, insitu PCR: 18 | 39 | 20 | Invasive (64), in situ (13) | NA | Fresh frozen DNA extract, human milk epithelial cell DNA, formalin-fixed specimens | Standard PCR, in situ PCR | EBNA-1 | 9 |
| Gupta et al., 2021 39 | Croatia | case-control | 70 | 16 | 25 | 0 | Triple-negative breast cancer | Grade I = 0Grade II = 11Grade III= 59 | Paraffin-embedded tissue | Thermo Scientific GeneJET FFPE DNA Purification Kit,PCR | EBNA1EBNA2LMP-1 | 7 |
| Hussein et al., 2013 40 | Iraq | case control | 22 | 10 | 11 | 0 | invasive (12), infiltrative (8), recurrent (2) | Grade I=4, Grade II=16, Grade III=2 | Paraffin-embedded tissue | ISH | EBER | 7 |
| Khabaz et al., 2013 42 | Saudi Arabia | case control | 92 | 49 | 24 | 3 | Invasive | Grade I=10, Grade II=32, Grade III=39; Grade III=7 | Paraffin-embedded tissue | PCR | EBER 2, BNLF-1, EBNA 2, Gp220, EBNA-1 | 6 |
| Metwally et al., 2021 43 | Egypt | case control | 80 | 30 | 23 | 0 | Invasive | Grade II=75, | paraffin-embedded tissue, fresh tissue samples, WBC | PCR | EBNA-1BXLF-1 BamH1-KLMP-1 | 5 |
| Mofrad et al., 2020 34 | Iran | case control | 59 | 11 | 4 | 0 | Invasive | I=4, II/III=55 | FFPE | PCR | EBV- EBNA, GAPDH | 8 |
| Morales-Sanchez et al,, 2013 48 | Mexico | case control | 86 | 65 | 4 | 0 | Invasive (79), in-situ (7) | na | FFPE | PCR | Raji, Daudi and B95-8 cells | 6 |
| Mostafaei et al., 2020 33 | Iran | case control | 83 | 31 | 50 | 11 | Invasive, in-situ | NA | FFPE | PCR | EBNA-2, LMP-1, LMP-2A, EBER 1, EBER 2 | 8 |
| Naushad et al., 2017 44 | Pakistan | Case-Control | 250 | 15 | 61 | 0 | Primary invasive breast cancer | grade 1 112 (44.8%) grade 2 113 (45.2%) grade 3 25 (10%) | paraffin embedded (FFPE) block | PCR | PCR: EBNA2F and EBNA2 | 4 |
| Pai et al., 2018 45 | India | Case-Control | 83 | 7 | 25 | 0 | Primary invasive breast cancer | Grade II 4 (4.8%) Grade III 79 (95.2%) | paraffin embedded tissues | ISH | ISH: EBER | 8 |
| Reza et al., 2015 31 | Iran | Case-Control | 100 | 100 | 8 | 0 | Primary invasive breast cancer | grade I (35%), grade II (42%), and grade III(23%) | Paraffin embedded block | PCR | PCR: EBER | 4 |
| Richardson et al., 2015 46 | New Zealand | Case-Control | 70 | 70 | 24 | 9 | N/A | Grade I: 8.5%Grade II: 29.6%Grade III: 62.0% | Frozen tissue | PCR | PCR: EBNA-1 | 6 |
| Sharifpour et al., 2019 32 | Iran | Case-Control | 37 | 35 | 10 | 4 | Invasive (34) In situ (3) | Grade I: 12 Grade II: 13 Grade III: 12 | Paraffin-Embedded Tissue | PCR | PCR: EBNA 3C | 7 |
| Torfi et al., 2021 30 | Iran | Case-Control | 46 | 46 | 2 | 0 | N/A | (I–II: 48%); (III–IV: 52%) | Not mentioned | PCR | PCR: EBNA-1 | 7 |
| Yahia et al., 2014 47 | Sudan | Case-Control | 92 | 50 | 59 | 12 | Primary invasive breast cancer | Not mentioned | Paraffin blocks and frozen tissue | PCR & ISH | PCR: EBNA-4 and LMP-1 | 6 |
| Zekri et al., 2012 41 | Egypt and Iraq | Case-Control | 90 | 40 | 32 | 0 | Primary invasive breast cancer | Grade I: 3, Grade II: 60, Grade III: 19 |
Paraffin blocks | PCR & ISH & IHC | PCR: EBNA-1 and LMP-1 ISH: EBER IHC: CD21 against EBV membrane receptor and LMP-1 | 7 |