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Table 6 Benefits and harms of the HPV vaccines: summary of new onset diseases

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

Summary of new onset diseasesaHPV vaccine total (N = 47,075)Comparator total (N = 48,595)Risk ratiof total [95% CI]Risk ratiof MSC [95% CI]Risk ratiof NMH [95% CI]
Total
 Participants with new onset diseasesb14,25814,0140.99 [0.97, 1.02]0.98 [0.90, 1.06]1.00 [0.97, 1.03]
  Follow-upc229623650.98 [0.94, 1.01]Not applicable0.98 [0.94, 1.01]
 Number of MedDRA-classified new onset diseasesb47,47446,662Not applicableNot applicableNot applicable
  Medically significant conditions (MSC)d7882 (17%)7994 (17%)Not applicableNot applicableNot applicable
  New medical history (NMH)e39,592 (83%)38,668 (83%)Not applicableNot applicableNot applicable
Most common new onset diseases (MedDRA-preferred terms, n = participants)
MSC
  Depression4434321.02 [0.89, 1.16]1.02 [0.85, 1.23]1.01 [0.84, 1.22]
  Genitourinary tract gonococcal infection1491620.92 [0.74, 1.15]0.91 [0.73, 1.14]1.15 [0.37, 3.52]
  Gynaecological chlamydia infection140915120.93 [0.87, 1.00]0.95 [0.88, 1.03]0.87 [0.76, 1.00]
NMH
  Vaginal candidiasis129713590.95 [0.89, 1.02]Not applicable0.95 [0.89, 1.02]
  Vaginitis bacterial118512040.98 [0.91, 1.06]Not applicable0.98 [0.91, 1.06]
  Urinary tract infection102310860.93 [0.86, 1.01]0.33 [0.01, 8.19]0.93 [0.86, 1.02]
New onset diseases most increased by the HPV vaccines (MedDRA-preferred terms, n = participants)
MSC
  Abdominal pain4333741.21 [0.98, 1.50]1.38 [1.00, 1.92]1.17 [0.87, 1.57]
  Back pain3973361.15 [1.00, 1.33]1.40 [1.05, 1.86]1.08 [0.91, 1.28]
  Headache7716931.06 [0.92, 1.22]1.29 [0.75, 2.24]1.04 [0.93, 1.15]
NMH
  Amenorrhoea3943591.09 [0.87, 1.37]0.66 [0.38, 1.15]1.17 [0.93, 1.48]
  Headache7716931.06 [0.92, 1.22]1.29 [0.75, 2.24]1.04 [0.93, 1.15]
  Joint sprain113831.18 [0.80, 1.75]0.60 [0.29, 1.22]1.45 [0.94, 2.24]
New onset diseases most decreased by the HPV vaccines (MedDRA-preferred terms, n = participants)
MSC
  Cystitis4805020.93 [0.77, 1.09]0.65 [0.44, 0.96]0.99 [0.87, 1.13]
  Gynaecological chlamydia infection140915120.93 [0.87, 1.00]0.95 [0.88, 1.03]0.87 [0.76, 1.00]
  Type 2 diabetes mellitus31470.89 [0.38, 2.09]0.62 [0.32, 1.20]3.00 [0.47, 19.02]
NMH
  Urinary tract infection102310860.93 [0.86, 1.01]0.33 [0.01, 8.19]0.93 [0.86, 1.02]
  Vaginal candidiasis129713590.95 [0.89, 1.02]Not applicable0.95 [0.89, 1.02]
  Vaginal infection3694200.87 [0.76, 1.00]Not applicable0.87 [0.76, 1.00]
  1. aSee Additional file 4 section 11 for meta-analyses of new onset diseases. The applied harm categories are MedDRA-preferred terms. New onset diseases consist of ‘medically significant conditions’ (MSC) and ‘new medical history’ (NMH). Numbers for ‘HPV vaccine’ and ‘comparator’ are the total of MSC and NMH. We divided new onset diseases for MSC and NMH, since the definitions for MSC and NMH differed (see Table 1). 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
  2. bThe clinical study reports reported 94,136 individual MedDRA-preferred term classified new onset diseases for 28,272 participants, i.e. 3.3 new onset diseases per participant. New onset diseases were reported as the number of participants over the total number of participants
  3. c‘Follow-up’ represents the trials V501-005, V501-019 and V501-020 that had dichotomized reporting of new medical history (NMH) into the vaccination period (day 0 to month 7) and follow-up period (from month 7 to the last day of follow-up). We included the vaccination periods for these trials in ‘participants with new onset diseases’ and included the follow-up periods in ‘follow-up’
  4. dGlaxoSmithKline defined ‘medically significant conditions’ as “Adverse events prompting emergency room or physician visits that are not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs [serious adverse events] that are not related to common diseases. Serious adverse events related to common diseases were reported but are not classified as medically significant conditions for analysis purposes. Common diseases include: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury”
  5. eMerck Sharp and Dohme did not provide a formal definition for ‘new medical history’ but described ‘new medical history’ as “all new reported diagnoses” in the clinical study report of trial V501-019
  6. fRisk ratios were calculated with the random-effects inverse variance method