Author, Year | Study population | Inclusion criteria | Adverse events | Vaccine group (%) | Control group (%) | P |
---|---|---|---|---|---|---|
Harper et al. 2004 [6] | N = 1113 women from 32 study sites in North America and Brazil. | 15–25 years ≤6 lifetime sexual partners No abnormal Pap test No external condylomata HPV 16/18 seronegative | 7-day period | N = 531 Gardasil | N = 538 Al(OH)3 | |
Injection-site symptoms Pain Swelling Redness General symptoms Fatigue Gastrointestinal Headache Itching Rash Fever | 499 (93.97) 496 (93.41) 182 (34.27) 189 (35.59) 458 (56.25) 308 (58.00) 178 (33.52) 331 (62.34) 130 (24.48) 60 (11.30) 88 (16.57) | 472 (87.73) 469 (87.17) 113 (21.00) 131 (24.35) 462 (85.87) 289 (53.72) 172 (31.97) 329 (61.15) 109 (20.26) 54 (10.04) 73 (13.57) | <0.001 <0.001 <0.001 <0.001 0.860 0.175 0.602 0.706 0.106 0.552 0.172 | |||
Entire study period (0–27 months) | ||||||
Vaccine-related serious adverse event Discontinuation for non-serious adverse event Discontinuation for serious adverse eventd | 0 0 1 (0.19) | 0 3 (0.56) 0 | 1.000 0.249 0.497 | |||
Villa et al. 2005 [7] | N = 277 women from Brazil, Europe, and USA | 16–23 years Non-pregnant No abnormal Pap smears ≤4 lifetime sex partners | N = 272 Gardasil | N = 274 AAHS | ||
Vaccine-associated adverse events Injection-site Systemic Vaccine-related serious adverse events Discontinued vaccination due to hypoaesthesia | 243 (89.34) 234 (86.03) 104 (38.24) 0 0 | 225 (82.12) 212 (77.37) 90 (32.85) 0 1 (0.36) | 0.016 0.009 0.188 1.000 0.319 | |||
Reisinger et al. 2007 [16] | N = 1781 children from 47 sites in 10 countries in North America, Latin America, Europe, and Asia, enrolled from December 2002 to September 2004 | 9–15 years old Sexually naïve Intact uterus No gross purulent cervicitis No genital warts No abnormal Pap smear No cervical intraepithelial neoplasia ≤4 lifetime sex partners Non-pregnant | 15-day period | N = 1165 Gardasil | N = 584 Saline | |
≥1 adverse events Injection-site adverse events Erythema Pain Swelling Systemic adverse events Serious vaccine-related adverse events | 963 (82.66) 877 (75.28) 237 (20.34) 853 (73.22) 241 (20.68) 541 (46.44) 0 | 392 (97.12) 292 (50.00) 77 (13.18) 265 (45.38) 45 (7.71) 260 (44.52) 0 | <0.001 <0.001 <0.001 <0.001 <0.001 0.448 1.000 | |||
N = 1157 | N = 579 | |||||
Fever | 1074 (92.83) | 541 (93.44) | 0.638 | |||
Merck V501-013 FUTURE I Study Garland et al. 2007 [2] | N = 5455 women at 62 study sites in 16 countries, enrolled from January 2002 to March 2003 | 16–24 year old Non-pregnant No history of genital warts No abnormal cervical cytology testing ≤4 lifetime sex partners Effective contraception | 5-day period | N = 2673 Gardasil | N = 2672 AAHS | |
Injection-site event Erythema Pain Pruritus Swelling | 2320 (86.79) 659 (24.65) 2281 (85.33) 109 (4.70) 694 (25.96) | 2068 (77.40) 450 (16.84) 2014 (75.37) 80 (2.99) 413 (15.46) | <0.001 <0.001 <0.001 <0.001 <0.001 | |||
15-day period | ||||||
Injection-related systemic event Pyrexia | 1161 (43.43) 361 (13.51) | 1085 (40.61) 272 (10.18) | 0.036 <0.001 | |||
Entire study period | ||||||
Vaccine-related serious eventa Discontinuation for vaccine-related event Death | 1 (0.03) 0 2 (0.07) | 0 0 2 (0.07) | 0.317 1.000 0.999 | |||
Merck V501-015 FUTURE II Study, 2007 [3] | N = 12,167 women in 13 countries, enrolled from June 2002 to March 2003 | 15–26 year old Non-pregnant No abnormal Papanicolaou smear ≤4 lifetime sex partners Effective contraception | 15-day period | N = 448 Gardasil | N = 447 AAHS | |
≥1 adverse event | ||||||
Injection-site event Pain Systemic event | 378 (84.38) 372 (83.04) 275 (61.38) | 348 (77.85) 339 (75.84) 268 (59.96) | 0.012 0.008 0.662 | |||
Entire study period | N = 6019 | N = 6031 | ||||
Serious injection-related eventb Discontinuation for serious injection-related event Death | 3 (0.05) 0 7 (0.12) | 2 (0.03) 0 5 (0.08) | 0.202 1.000 0.338 | |||
Muñoz et al. 2009 [8] | N = 3819 women from 38 international sites in Colombia, France, Germany, Philippines, Spain, Thailand, and USA | 24–45 year old Non-pregnant Intact uterus No genital warts or cervical disease HIV seronegative | 15-day period | N = 1889 Gardasil | N = 1886 AAHS | |
Vaccine-related adverse events Injection-site adverse events Systemic adverse events Serious vaccine-related adverse events | 1565 (82.84) 1449 (76.71) 745 (39.44) 0 | 1389 (73.65) 1212 (64.26) 695 (36.85) 0 | <0.001 <0.001 0.102 1.000 | |||
Bhatla et al. 2010 [9] | N = 330 women at four teaching/ tertiary care hospitals across India, enrolled from July 2006 to March 2007 | Non-pregnant No investigational products/ steroids Contraception or sexual abstinence | 7-day period | N = 171 Cervarix | N = 174 Al(OH)3 | |
Pain, all-type Grade 3 Pain Redness, any size >50 mm Swelling, any size >50 mm Grade 3 solicited general symptoms Medically significant adverse event Serious adverse events Acute pancreatitis Lymph node tuberculosis Bronchogenic cyst Cataract Miscarriage Pneumothorax Death | 137 (80.12) 35 (20.47) 56 (32.75) 1 (0.58) 69 (40.35) 5 (2.92) 11 (6.43) 13 (7.60) 2 (1.717) 1 (0.58) 1 (0.58) 0 0 0 0 0 | 105 (60.34) 7 (4.02) 24 (13.79) 1 (0.57) 35 (20.11) 3 (1.72) 10 (5.75) 24 (13.79) 4 (2.30) 0 0 1 (0.57) 1 (0.57) 1 (0.57) 1 (0.57) 0 | <0.001 <0.001 <0.001 0.990 <0.001 0.459 0.790 0.063 0.422 0.312 0312 0.321 0.321 0.321 0.321 1.00 | |||
Ngan et al. 2010 [10] | N = 300 women at a single center in Hong Kong | 18–35 year old No chronic disease Non-pregnant/ breastfeeding | Entire study period | N = 145 Cervarix | N = 145 Al(OH)3 | |
Abdominal pain, IBS, dizziness, headache Pelvic inflammatory disease Medically significant conditions New onset chronic disease | 3 (2.07) 0 42 (2.90) 7 (4.83) | 0 1 (0.69) 24 (16.55) 5 (3.44) | 0.082 0.316 0.012 0.555 | |||
Levin et al. 2010 [11] | N = 126 children HIV-seropositive children | 7–12 years old HIV with CD4 ≥ 15 % ≥3 months HAART if CD4 < 25 % | 14-day period | N = 96 Gardasil | N = 30 Saline Placebo | |
Adverse events Ear, eye, respiratory symptom Injection-site reactions Laboratory abnormality Systemic reactions Other | 35 (36.46) 1 (1.04) 21 (21.89) 3 (3.13) 2 (2.08) 1 (1.04) | 15 (50.00) 1 (3.33) 3 (10.00) 1 (3.33) 1 (3.33) 1 (3.33) | 0.186 0.381 0.148 0.955 0.695 0.381 | |||
V501-20 | N = 4065 males from 71 sites in 18 countries | 16–26 years old 1–5 male or female sexual partners No anogenital lesions | 15-day period | N = 1945 Gardasil | N = 1950 AAHS | |
Vaccine-related events Injection-site Systemic Vaccine-related serious events Death Discontinuation for vaccine-related adverse evente | 1242 (63.86) 1169 (60.10) 274 (14.09) 0 0 2 (0.10) | 1134 (58.15) 1046 (53.64) 284 (14.56) 0 0 3 (0.15) | <0.001 <0.001 0.67 1.000 1.000 0.657 | |||
Entire study period | ||||||
Vaccine-related events Injection-site Systematic Vaccine-related serious events Death Discontinuation for vaccine-related adverse evente | 1242 (63.86) 1169 (60.10) 274 (14.09) 0 3 2 (0.10) | 1134 (58.15) 1046 (53.64) 284 (14.56) 0 10 3 (0.15) | <0.001 <0.001 0.67 1.00 0.052 0.657 | |||
Sow et al. 2013 [13] | N = 676 women in 2 centers in sub-Saharan Africa (Senegal and Tanzania) from October 2007 to July 2010 | 10–25 years old HIV seronegative Not pregnant ≤6 lifetime sexual partners | 0–12 months* | N = 450 Cervarix | N = 226 Al(OH)3 | |
Grade 3 injection-site pain Serious adverse eventc Medically significant condition New onset chronic disease New onset autoimmune disease Deaths Premature births- infant death | 2 (0.44) 17 (3.78) 312 (69.33) 11 (2.44) 2 (0.44) 0 1 (0.22) | 0 14 (6.19) 170 (75.22) 11 (4.87) 2 (0.88) 0 1 (0.44) | 0.316 0.156 0.110 0.094 0.481 1.000 0.619 | |||
Yoshikawa et al. 2013 [14] | N = 1030 Japanese women, multicenter | 18–26 years old Not pregnant No previous abnormal Pap smears ≤4 males sex partners Effective contraception | Days 1–15 | N = 480 Gardasil | N = 468 AAHS | |
All-type adverse event Injection-site adverse event Systemic adverse event Serious adverse event Discontinuation for vaccine-related adverse eventf Death | 417 (86.88) 408 (85.00) 66 (13.75) 0 1 (0.21) 0 | 347 (74.15) 338 (72.22) 53 (11.32) 0 0 0 | <0.001 <0.001 0.260 1.000 1.000 | |||
Denny et al. 2013 [15] | N = 150 women at a single center in Khayelitsha, Cape Town, Republic of South Africa. | 18–25 years old ≤6 lifetime sexual partners Non-pregnant Intact cervix | 30-day period | N = HIV 61 (+)/30 (-) Cervarix | N = 59 HIV(+) Al(OH)3 | |
Unsolicited adverse event Headache Upper respiratory tract infection Lobar Pneumonia (Grade 3) Bacterial Pneumonia (Grade 3) | 53 (86.89)/ 26 (86.67) 12 (19.67)/ 4 (13.33) 10 (16.39)/ 7 (23.33) 1 (1.64)/ 0 (0.00) 0/ 0 | 46 (77.97) 14 (23.73) 10 (16.95) 0 1 (1.69) | 0.199 0.590 0.935/0.390 0.323/1.000 0.311/0.473 | |||
Up to 7 months | ||||||
Medically significant adverse event | 18 (29.51)/5 (16.67) | 21 (35.59) | 0.477/0.063 | |||
7–12 months | N = HIV54 (+)/ 24 (-) | N = 52 HIV(+) | ||||
Medically significant adverse event Discontinuation for vaccine-related adverse event | 6 (11.11)/ 2 (8.33) 0/ 0 | 5 (9.62) 0 | 0.801/0.857 1.000 |