Table 1. Characteristics of the 32 studies included in the meta-analysis.
| First author, year | Country | Period | Histology | Detection method | Cutoff value for detection | No. of subjects (LMP1+/LMP1−) | Median/mean age (range) | Median/mean follow-up time (months) | Quality score | HR (95% CI) for overall survival |
|---|---|---|---|---|---|---|---|---|---|---|
| NPC | ||||||||||
| Chen, 2010 | China | 1992–2002 | NPC | IHC | IRS, ≥4 | 224 (141/83) | 46 (14–86) | NA | 8 | 2.06 (1.16–3.64) |
| Hariwiyanto, 2010 | Indonesia | NA | NPC | IHC | H-score, >7 | 56 (27/29) | (11–70)* | NA | 7 | 5.56 (1.87–16.50) |
| Kitagawa, 2013 | Japan | 1998–2009 | NPC | IHC | Percentage, ≥10% | 74 (35/39) | Median >50 | 45.24 | 7 | 1.26 (0.69–2.28) |
| Li, 2009 | China | 1999–2003 | NPC | IHC | Percentage × staining intensity, ≥1 | 57 (24/33) | 56.2 (22–72) | 36 | 8 | 2.73 (0.91–8.17) |
| Sarac, 2001 | Turkey | 1979–1993 | Un differentiated NPC | IHC | Positive: detectable | 35 (10/25) | 35 (5–71) | 66 | 7 | 2.82 (0.88–8.98) |
| Song, 2007 | China | 2001–2003 | NPC | IHC | Percentage, ≥10% | 50 (25/25) | 50.24* | NA | 8 | 4.72 (1.45–15.33) |
| Wang, 2008 | China | 1999–2003 | Nonkeratin NPC | IHC | Percentage, ≥25% | 60 (24/36) | 53 (18–79) | 36–74 | 8 | 3.17 (1.37–7.31) |
| Zhu, 2004 | China | 1990–1991 | Un differentiated NPC | IHC | Percentage × staining intensity, ≥1 | 60 (39/21) | 38 (13–65) | 56 | 8 | 2.80 (1.30–6.04) |
| NHL | ||||||||||
| Cao, 2008 | China | 1994–2000 | ENKL | IHC | Percentage, ≥ 10% | 58 (47/11) | 45.4 (10–78) | 84 | 7 | 2.59 (1.01–6.67) |
| Hirose, 2006 | Japan | 1980–2004 | PTCL | IHC | NA | 43 (14/29) | 63 (17–86) | 14 | 6 | 1.68 (0.80–3.54) |
| Ishii, 2007 | Japan | 1990–2003 | ENKL | PCR | >40 copies/ml | 20 (13/7) | 52.5 (28–71) | 34 | 7 | 7.02 (1.91–25.73) |
| Kanemitsu, 2012 | Japan | 1996–2010 | ENKL | IHC | NA | 30 (22/8) | 62 (27–85) | 26.7 | 6 | 0.24 (0.07–0.80) |
| Kuze, 1996 | Japan | 1983–1995 | BCL | IHC | NA | 17 (6/11) | 60 (35–82) | 12 | 5 | 0.85 (0.19–3.82) |
| Paydas, 2008 | Turkey | NA | NHL | IHC | NA | 138 (20/118) | 51.6 (16–82) | NA | 5 | 3.49 (1.68–7.25) |
| Xu, 2009 | China | 1995–2005 | ENKL | IHC | Percentage × staining intensity, ≥1 | 62 (30/32) | 41 (13–79) | NA | 7 | 1.73 (0.86–3.46) |
| Yamamoto,1999 | Japan | 1974–1994 | TCL | ISH | mRNA positive in tumor cells | 25 (15/10) | NA | >36 | 7 | 3.80 (0.92–15.80) |
| Zhao, 2005 | China | 2000–2004 | ENKL | IHC | Positive: detectable | 36 (6/30) | 40 (16–71) | 17.7 | 7 | 1.28 (0.40–4.02) |
| HD | ||||||||||
| Clarke, 2001 | USA | 1988–1994 | HL | IHC | NA | 78 (51/27)†‡ | (45–79)* | 73 | 6 | 3.00 (1.50–6.40) |
| Claviez, 2005 | Germany & Austria | 1990–2001 | HL | IHC | NA | 842 (263/579) | 13.7 (2.2–20.2) | 58.5 | 7 | 3.00 (1.22–7.39) |
| Dinand, 2009 | India | 1991–2004 | cHL | IHC | Percentage, ≥25% | 122 (113/9) | 8 (2–14) | 48 | 7 | 0.60 (0.10–4.90) |
| Enblad, 1999 | Sweden | 1985–1988 | HL | IHC | NA | 117 (32/85) | 45 (11–87) | 130 | 7 | 2.06 (0.71–6.00) |
| Engel, 2000 | South Africa | NA | HL | IHC | NA | 36 (24/12)‡ | 8 (3–14) | 4–150 | 7 | 0.08 (0.02–0.45) |
| Glavina-Durdov, 2001 | Croatia | 1980–1990 | HL | IHC | NA | 100 (26/74) | 40 (13–84) | NA | 7 | 0.98 (0.42–2.32) |
| Herling, 2003 | USA& Italy & Greece | 1984–2000 | cHL | IHC | Positive: detectable | 303 (61/242) | 30* | 65 | 7 | 1.11 (0.50–2.45) |
| Keresztes, 2005 | Hungary | NA | HL | IHC | NA | 109 (47/62) | 31 (3–74) | 83 | 6 | 2.13 (0.74–6.15) |
| Krugmann, 2003 | Austria | 1974–1999 | cHL | IHC | NA | 119 (31/88) | 37.6 (14–83) | 122 | 7 | 0.96 (0.39–2.33) |
| Morente, 1997 | Spain | NA | HL | IHC | Positive: detectable | 140 (72/68) | 37.2 (5–83) | 65 | 8 | 0.39 (0.17–0.92) |
| Murray, 1999 | UK | 1992–1996 | HL | IHC | NA | 161 (41/120) | 33 (22–49) | 86 | 6 | 0.71 (0.32–1.57) |
| Naresh, 2000 | India | 1984–1988 | cHL | IHC | Percentage, ≥10% | 110 (86/24)‡ | 22 (4–61) | 57 | 6 | 0.26 (0.08–0.88) |
| Quijano, 2004 | Colombia | 1994–1998 | HL | IHC | NA | 57 (32/25) | (3–83)* | 23.8 | 6 | 0.36 (0.08 -1.60) |
| Stark, 2002 | UK | 1991–1998 | HL | IHC | NA | 70 (24/46) | (60–91)* | 62.5 | 8 | 3.12 (1.36–7.11) |
| GC | ||||||||||
| Lee, 2004 | Korea | 1995–1996 | GC | IHC | Percentage, ≥10% | 343 (63/280)‡ | 55* | 54 | 6 | 0.70 (0.44–1.13) |
Abbreviations: cHL, classical Hodgkin lymphoma; CI, confidence interval; ENKL, extranodal NK/T-cell lymphoma, nasal type; GC, gastric cancer; HD, Hodgkin disease; HR, hazard ratio; H-score, histochemistry score; IHC, immunohistochemistry; IRS, immunoreactive score; ISH, in situ hybridization; LMP1, latent membrane protein 1; NA, not available; NHL, non-Hodgkin lymphoma; NPC, nasopharyngeal carcinoma; PCR, polymerase chain reaction; PTCL, peripheral T-cell lymphomas; TCL, T-cell lymphoma.
Median/mean age or range is not available.
The survival data was only available for patients aged older than 45 years.
The positive/negative cases in these studies were positive/negative for Epstein-Barr virus encoded nuclear RNA-1 (EBER-1) as detected by in situ hybridization. The positive rates of LMP1 detected by IHC were 69%, 90%, 65%, and 93% in the EBER-1 positive cases in the studies by Clarke, Engel, Naresh, and Lee, respectively.