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Table 8 Benefits and harms of the HPV vaccines: summary of exploratory harm analyses by MedDRA system organ class

From: Benefits and harms of the human papillomavirus (HPV) vaccines: systematic review with meta-analyses of trial data from clinical study reports

Summary of exploratory harm analyses by MedDRA system organ classaFatal harmsSerious harmsNew onset diseasesbGeneral 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 disorders00Not applicable11120.97 [0.44, 2.18]4244211.00 [0.88, 1.15]17101.33 [0.56, 3.15]
Cardiac disorders1352.45 [0.87, 6.87]28211.12 [0.49, 2.55]108861.09 [0.67, 1.78]650.89 [0.26, 2.99]
Congenital, familial and genetic disorders00Not applicable190.32 [0.09, 1.13]50670.74 [0.51, 1.06]010.55 [0.02, 13.40]
Ear and labyrinth disorders00Not applicable460.68 [0.19, 2.45]1541391.04 [0.78, 1.39]54401.10 [0.71, 1.69]
Endocrine disorders102.83 [0.12, 69,36]741.60 [0.48, 5.35]1892070.91 [0.74, 1.10]110.72 [0.04, 11.85]
Eye disorders00Not applicable641.51 [0.42, 5.37]2963260.89 [0.76, 1.04]40390.84 [0.53, 1.33]
Gastrointestinal disorders102.83 [0.12, 69,36]107921.12 [0.85, 1.48]222621411.05 [0.95, 1.16]408537351.09 [1.01, 1.17]
General disorders00Not applicable1391.45 [0.60, 3.50]5634831.14 [1.01, 1.28]640158421.10 [1.04, 1.17]
Hepatobiliary disorders110.94 [0.06, 15.06]52481.03 [0.70, 1.52]1261430.86 [0.61, 1.22]212.00 [0.18, 22.00]
Immune system disorders102.83 [0.12, 69,36]9140.68 [0.30, 1.58]3713980.92 [0.78, 1.08]35241.29 [0.76, 2.18]
Infections and infestations851.51 [0.49, 4.61]4003671.04 [0.80, 1.37]897090250.98 [0.96, 1.00]11419651.14 [1.00, 1.30]
Injury, poisoning and procedural complications16180.84 [0.43, 1.64]1992240.85 [0.64, 1.13]120512090.94 [0.82, 1.06]1421221.03 [0.81, 1.33]
Investigations00Not applicable120.69 [0.11, 4.40]143814291.00 [0.94, 1.07]741.34 [0.41, 4.41]
Metabolism and nutrition disorders110.94 [0.06, 15.06]19111.44 [0.72, 2.89]3423550.95 [0.82, 1.10]17150.98 [0.49, 1.96]
Musculoskeletal and connective tissue disorders204.71 [0.23, 98.09]35311.07 [0.66, 1.74]126312131.02 [0.94, 1.10]600546831.34 [1.21, 1.49]
Neoplasms benign, malignant and unspecified1343.06 [1.00, 9.39]68561.20 [0.84, 1.71]4664211.09 [0.96, 1.25]220.71 [0.14, 3.51]
Nervous system disorders413.77 [0.42, 33.71]72461.49 [1.02, 2.16]141013051.06 [0.97, 1.16]596754221.09 [1.04, 1.14]
Pregnancy, puerperium and perinatal conditions00Not applicable4584261.08 [0.94, 1.23]7267141.02 [0.92, 1.12]102.91 [0.12, 68.66]
Psychiatric disorders480.47 [0.14, 1.56]80870.92 [0.68, 1.25]9619590.99 [0.91, 1.08]49530.90 [0.61, 1.33]
Renal and urinary disorders211.88 [0.17, 20.77]19171.07 [0.57, 2.01]4043951.01 [0.88, 1.16]1261.32 [0.48, 3.59]
Reproductive system and breast disorders204.71 [0.23, 98.09]72780.90 [0.65, 1.24]345834630.99 [0.95, 1.04]2131581.13 [0.92, 1.38]
Respiratory, thoracic and mediastinal disorders321.41 [0.24, 8.45]44341.26 [0.81, 1.97]7957711.00 [0.91, 1.11]4643941.02 [0.89, 1.18]
Skin and subcutaneous tissue disorders102.83 [0.12, 69.36]1271.48 [0.60, 3.63]117311760.99 [0.88, 1.12]9977711.21 [1.03, 1.44]
Social circumstances220.94 [0.13, 6.69]220.95 [0.14, 6.50]46420.95 [0.62, 1.47]111.00 [0.10, 9.60]
Surgical and medical procedures00Not applicable651.15 [0.36, 3.67]131813400.97 [0.90, 1.04]00Not applicable
Vascular disorders431.26 [0.28, 5.61]16160.96 [0.47, 1.99]2342940.80 [0.67, 0.94]11120.68 [0.28, 1.63]
  1. 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)
  2. 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)
  3. 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
  4. dRisk ratios were calculated with the random-effects inverse variance method