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. 2020 Feb 28;9:43. doi: 10.1186/s13643-019-0983-y

Table 8.

Benefits and harms of the HPV vaccines: summary of exploratory harm analyses by MedDRA system organ class

Summary of exploratory harm analyses by MedDRA system organ classa Fatal harms Serious harms New onset diseasesb General harmsc
HPV vaccine (N = 47,075) Comparator (N = 48,595) Risk ratiod [95% CI] HPV vaccine (N = 47,075) Comparator (N = 48,595) Risk ratiod[95% CI] HPV vaccine (N = 47,075) Comparator (N = 48,595) Risk ratiod [95% CI] HPV vaccine (N = 47,075) Comparator (N = 48,595) Risk ratiod [95% CI]
Blood and lymphatic system disorders 0 0 Not applicable 11 12 0.97 [0.44, 2.18] 424 421 1.00 [0.88, 1.15] 17 10 1.33 [0.56, 3.15]
Cardiac disorders 13 5 2.45 [0.87, 6.87] 28 21 1.12 [0.49, 2.55] 108 86 1.09 [0.67, 1.78] 6 5 0.89 [0.26, 2.99]
Congenital, familial and genetic disorders 0 0 Not applicable 1 9 0.32 [0.09, 1.13] 50 67 0.74 [0.51, 1.06] 0 1 0.55 [0.02, 13.40]
Ear and labyrinth disorders 0 0 Not applicable 4 6 0.68 [0.19, 2.45] 154 139 1.04 [0.78, 1.39] 54 40 1.10 [0.71, 1.69]
Endocrine disorders 1 0 2.83 [0.12, 69,36] 7 4 1.60 [0.48, 5.35] 189 207 0.91 [0.74, 1.10] 1 1 0.72 [0.04, 11.85]
Eye disorders 0 0 Not applicable 6 4 1.51 [0.42, 5.37] 296 326 0.89 [0.76, 1.04] 40 39 0.84 [0.53, 1.33]
Gastrointestinal disorders 1 0 2.83 [0.12, 69,36] 107 92 1.12 [0.85, 1.48] 2226 2141 1.05 [0.95, 1.16] 4085 3735 1.09 [1.01, 1.17]
General disorders 0 0 Not applicable 13 9 1.45 [0.60, 3.50] 563 483 1.14 [1.01, 1.28] 6401 5842 1.10 [1.04, 1.17]
Hepatobiliary disorders 1 1 0.94 [0.06, 15.06] 52 48 1.03 [0.70, 1.52] 126 143 0.86 [0.61, 1.22] 2 1 2.00 [0.18, 22.00]
Immune system disorders 1 0 2.83 [0.12, 69,36] 9 14 0.68 [0.30, 1.58] 371 398 0.92 [0.78, 1.08] 35 24 1.29 [0.76, 2.18]
Infections and infestations 8 5 1.51 [0.49, 4.61] 400 367 1.04 [0.80, 1.37] 8970 9025 0.98 [0.96, 1.00] 1141 965 1.14 [1.00, 1.30]
Injury, poisoning and procedural complications 16 18 0.84 [0.43, 1.64] 199 224 0.85 [0.64, 1.13] 1205 1209 0.94 [0.82, 1.06] 142 122 1.03 [0.81, 1.33]
Investigations 0 0 Not applicable 1 2 0.69 [0.11, 4.40] 1438 1429 1.00 [0.94, 1.07] 7 4 1.34 [0.41, 4.41]
Metabolism and nutrition disorders 1 1 0.94 [0.06, 15.06] 19 11 1.44 [0.72, 2.89] 342 355 0.95 [0.82, 1.10] 17 15 0.98 [0.49, 1.96]
Musculoskeletal and connective tissue disorders 2 0 4.71 [0.23, 98.09] 35 31 1.07 [0.66, 1.74] 1263 1213 1.02 [0.94, 1.10] 6005 4683 1.34 [1.21, 1.49]
Neoplasms benign, malignant and unspecified 13 4 3.06 [1.00, 9.39] 68 56 1.20 [0.84, 1.71] 466 421 1.09 [0.96, 1.25] 2 2 0.71 [0.14, 3.51]
Nervous system disorders 4 1 3.77 [0.42, 33.71] 72 46 1.49 [1.02, 2.16] 1410 1305 1.06 [0.97, 1.16] 5967 5422 1.09 [1.04, 1.14]
Pregnancy, puerperium and perinatal conditions 0 0 Not applicable 458 426 1.08 [0.94, 1.23] 726 714 1.02 [0.92, 1.12] 1 0 2.91 [0.12, 68.66]
Psychiatric disorders 4 8 0.47 [0.14, 1.56] 80 87 0.92 [0.68, 1.25] 961 959 0.99 [0.91, 1.08] 49 53 0.90 [0.61, 1.33]
Renal and urinary disorders 2 1 1.88 [0.17, 20.77] 19 17 1.07 [0.57, 2.01] 404 395 1.01 [0.88, 1.16] 12 6 1.32 [0.48, 3.59]
Reproductive system and breast disorders 2 0 4.71 [0.23, 98.09] 72 78 0.90 [0.65, 1.24] 3458 3463 0.99 [0.95, 1.04] 213 158 1.13 [0.92, 1.38]
Respiratory, thoracic and mediastinal disorders 3 2 1.41 [0.24, 8.45] 44 34 1.26 [0.81, 1.97] 795 771 1.00 [0.91, 1.11] 464 394 1.02 [0.89, 1.18]
Skin and subcutaneous tissue disorders 1 0 2.83 [0.12, 69.36] 12 7 1.48 [0.60, 3.63] 1173 1176 0.99 [0.88, 1.12] 997 771 1.21 [1.03, 1.44]
Social circumstances 2 2 0.94 [0.13, 6.69] 2 2 0.95 [0.14, 6.50] 46 42 0.95 [0.62, 1.47] 1 1 1.00 [0.10, 9.60]
Surgical and medical procedures 0 0 Not applicable 6 5 1.15 [0.36, 3.67] 1318 1340 0.97 [0.90, 1.04] 0 0 Not applicable
Vascular disorders 4 3 1.26 [0.28, 5.61] 16 16 0.96 [0.47, 1.99] 234 294 0.80 [0.67, 0.94] 11 12 0.68 [0.28, 1.63]

aSee Additional file 4 sections 9 to 12 for meta-analyses of MedDRA system organ classes. Only Merck clinical study reports aggregated data for MedDRA system organ classes per participant and only for new onset diseases (‘new medical history’) and general harms (‘systemic adverse events’). A participant may have been counted more than once in the MedDRA system organ class analyses of GlaxoSmithKline clinical study reports and in analyses of fatal and serious harms; we therefore consider these analyses exploratory. Risk ratios for GlaxoSmithKline and Merck studies are provided separately in Additional file 4. It was not feasible to present this summary table for the 16 subgroups (based on age group, gender, type of HPV vaccine and comparator) of the 24 included clinical study reports. To avoid double counting of participants in the total risk ratio estimate we only included the new onset diseases reported in the vaccination period for the trials V501-005, V501-019 and V501-020, and we only included solicited adverse events when studies also reported unsolicited adverse events (see Additional file 4)

bNew onset diseases were compiled of the harm categories ‘medically significant conditions’ (for Cervarix) and ‘new medical history’ (for Gardasil, Gardasil 9 and the HPV 16 vaccine)

cGeneral harms were compiled of the harm categories ‘solicited general adverse events’, ‘unsolicited general adverse events’ (for Cervarix) and ‘systemic adverse events’ (for Gardasil, Gardasil 9 and the HPV 16 vaccine). To avoid double counting of participants, ‘unsolicited general adverse events’ were dismissed from the total risk ratio for studies that reported SGAE and UGAE separately

dRisk ratios were calculated with the random-effects inverse variance method