Skip to main content

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 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]

  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
Back to article page

Systematic Reviews

ISSN: 2046-4053