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Table 7 Benefits and harms of the HPV vaccines: summary of general harms

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

Summary of general harmsaHPV vaccine total (N = 47,075)Comparator total (N = 48,595)Risk ratiof total [95% CI]Risk ratiof SGAE [95% CI]Risk ratiof UGAE [95% CI]Risk ratiof SYAE [95% CI]
Total
 Participants with general harmsb13,24812,3941.07 [1.03, 1.11]1.11 [1.06, 1.16]g1.11 [1.06, 1.16]g1.01 [0.98, 1.03]
 Number of MedDRA-classified general harmsb37,99931,916Not applicableNot applicableNot applicableNot applicable
  Solicited general adverse events (SGAE)c30,408 (80%)25,300 (79%)Not applicableNot applicableNot applicableNot applicable
  Unsolicited general adverse events (UGAE)d3197 (8%)3136 (10%)Not applicableNot applicableNot applicableNot applicable
  Systemic adverse events (SYAE)e4394 (12%)3480 (11%)Not applicableNot applicableNot applicableNot applicable
Most common general harms (MedDRA-preferred terms, n = participants)
SGAE and UGAE
  Fatigue493344891.13 [1.08, 1.18]1.14 [1.09, 1.19]1.00 [0.15, 6.53]0.92 [0.70, 1.20]
  Headache556152461.06 [1.02, 1.11]1.08 [1.03, 1.14]1.76 [1.26, 2.47]0.98 [0.90, 1.07]
  Myalgia398930471.41 [1.24, 1.60]1.42 [1.24, 1.63]1.15 [0.24, 5.57]1.33 [0.95, 1.85]
SYAE
  Headache556152461.06 [1.02, 1.11]1.08 [1.03, 1.14]1.76 [1.26, 2.47]0.98 [0.90, 1.07]
  Pyrexia159913861.12 [1.02, 1.22]1.15 [1.06, 1.25]1.47 [0.93, 2.34]1.05 [0.80, 1.36]
  Nasopharyngitis3392771.17 [0.91, 1.50]Not applicable1.40 [0.94, 2.09]0.95 [0.78, 1.16]
General harms most increased by the HPV vaccines (MedDRA-preferred terms, n = participants)
SGAE and UGAE
  Fatigue493344891.13 [1.08, 1.18]1.14 [1.09, 1.19]1.00 [0.15, 6.53]0.92 [0.70, 1.20]
  Headache556152461.06 [1.02, 1.11]1.08 [1.03, 1.14]1.76 [1.26, 2.47]0.98 [0.90, 1.07]
  Myalgia398930471.41 [1.24, 1.60]1.42 [1.24, 1.63]1.15 [0.24, 5.57]1.33 [0.95, 1.85]
SYAE
  Myalgia398930471.41 [1.24, 1.60]1.42 [1.24, 1.63]1.15 [0.24, 5.57]1.33 [0.95, 1.85]
  Nausea2131481.21 [0.89, 1.65]Not applicable1.32 [0.35, 4.98]1.25 [0.84, 1.86]
  Pyrexia159913861.12 [1.02, 1.22]1.15 [1.06, 1.25]1.47 [0.93, 2.34]1.05 [0.80, 1.36]
General harms most decreased by the HPV vaccines (MedDRA-preferred terms, n = participants)
SGAE and UGAE
  Influenza1191200.91 [0.61, 1.36]Not applicable0.88 [0.39, 1.97]0.94 [0.56, 1.58]
  Cough86870.89 [0.65, 1.21]Not applicable0.83 [0.46, 1.49]0.90 [0.60, 1.37]
  Oropharyngeal pain111971.10 [0.80, 1.50]Not applicable0.91 [0.58, 1.43]1.29 [0.75, 2.22]
SYAE      
  Fungal infection4110.78 [0.09, 6.43]Not applicable3.01 [0.31, 28.83]0.18 [0.04, 0.82]
  Sinus headache9150.49 [0.21, 1.14]Not applicableNot applicable0.49 [0.21, 1.14]
  Joint injury250.47 [0.11, 2.01]Not applicable3.01 [0.31, 28.83]0.15 [0.03, 0.88]
  1. aSee Additional file 4 section 12 for meta-analyses of general harms for the 16 subgroups (based on age group, type of HPV vaccine and comparator) of the 24 included clinical study reports. The applied harm categories are MedDRA-preferred terms. The table contains general harms of ‘solicited general adverse events’ (SGAE), ‘unsolicited general adverse events’ (UGAE) and ‘systemic adverse events’ (SYAE). Numbers for ‘HPV vaccine’ and ‘comparator’ are the total of SGAE, UGAE and SYAE, but to avoid double counting of participants, UGAE (that accounted for less than 10% of the general harms) were dismissed from the total risk ratio for studies that reported SGAE and UGAE separately (SGAE and UGAE were not reported as pooled estimates for individual general harms classified with MedDRA-preferred terms; see Additional file 4). It was not feasible to present this summary table for the 16 subgroups (based on age group, type of HPV vaccine and comparator) of the 24 included clinical study reports
  2. bThe clinical study reports reported 69,915 individual MedDRA-classified general harms for 25,642 participants, i.e. 2.7 general harms per participant. General harms were reported as the number of participants with a MedDRA-classified general harm over the total number of participants
  3. cGlaxoSmithKline defined ‘solicited general adverse events’ (SGAE) as “Adverse events to be recorded [from day 0 to day 6 after each vaccination] as endpoints [arthralgia, fatigue, headache, myalgia, pyrexia, rash and urticaria] in the clinical study”
  4. dGlaxoSmithKline defined ‘unsolicited general adverse events’ (UGAE) as “Any AE [adverse event] reported in addition to those solicited during the clinical study. Also, any “solicited” symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited AE”
  5. eMerck Sharp and Dohme defined ‘systemic adverse events’ (SYAE) as “any systemic clinical adverse event that developed on the day of vaccination or during the 14 days after vaccination was recorded on the VRC [vaccination report card]”
  6. fRisk ratios were calculated with the random-effects inverse variance method
  7. gThe total numbers of participants with general harms in Cervarix studies were reported as ‘solicited [SGAE] and unsolicited [UGAE]’, i.e. the risk ratio is similar for SGAE and UGAE