Table 6.
Benefits and harms of the HPV vaccines: summary of new onset diseases
| Summary of new onset diseasesa | HPV 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 diseasesb | 14,258 | 14,014 | 0.99 [0.97, 1.02] | 0.98 [0.90, 1.06] | 1.00 [0.97, 1.03] |
| Follow-upc | 2296 | 2365 | 0.98 [0.94, 1.01] | Not applicable | 0.98 [0.94, 1.01] |
| Number of MedDRA-classified new onset diseasesb | 47,474 | 46,662 | Not applicable | Not applicable | Not applicable |
| Medically significant conditions (MSC)d | 7882 (17%) | 7994 (17%) | Not applicable | Not applicable | Not applicable |
| New medical history (NMH)e | 39,592 (83%) | 38,668 (83%) | Not applicable | Not applicable | Not applicable |
| Most common new onset diseases (MedDRA-preferred terms, n = participants) | |||||
| MSC | |||||
| Depression | 443 | 432 | 1.02 [0.89, 1.16] | 1.02 [0.85, 1.23] | 1.01 [0.84, 1.22] |
| Genitourinary tract gonococcal infection | 149 | 162 | 0.92 [0.74, 1.15] | 0.91 [0.73, 1.14] | 1.15 [0.37, 3.52] |
| Gynaecological chlamydia infection | 1409 | 1512 | 0.93 [0.87, 1.00] | 0.95 [0.88, 1.03] | 0.87 [0.76, 1.00] |
| NMH | |||||
| Vaginal candidiasis | 1297 | 1359 | 0.95 [0.89, 1.02] | Not applicable | 0.95 [0.89, 1.02] |
| Vaginitis bacterial | 1185 | 1204 | 0.98 [0.91, 1.06] | Not applicable | 0.98 [0.91, 1.06] |
| Urinary tract infection | 1023 | 1086 | 0.93 [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 pain | 433 | 374 | 1.21 [0.98, 1.50] | 1.38 [1.00, 1.92] | 1.17 [0.87, 1.57] |
| Back pain | 397 | 336 | 1.15 [1.00, 1.33] | 1.40 [1.05, 1.86] | 1.08 [0.91, 1.28] |
| Headache | 771 | 693 | 1.06 [0.92, 1.22] | 1.29 [0.75, 2.24] | 1.04 [0.93, 1.15] |
| NMH | |||||
| Amenorrhoea | 394 | 359 | 1.09 [0.87, 1.37] | 0.66 [0.38, 1.15] | 1.17 [0.93, 1.48] |
| Headache | 771 | 693 | 1.06 [0.92, 1.22] | 1.29 [0.75, 2.24] | 1.04 [0.93, 1.15] |
| Joint sprain | 113 | 83 | 1.18 [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 | |||||
| Cystitis | 480 | 502 | 0.93 [0.77, 1.09] | 0.65 [0.44, 0.96] | 0.99 [0.87, 1.13] |
| Gynaecological chlamydia infection | 1409 | 1512 | 0.93 [0.87, 1.00] | 0.95 [0.88, 1.03] | 0.87 [0.76, 1.00] |
| Type 2 diabetes mellitus | 31 | 47 | 0.89 [0.38, 2.09] | 0.62 [0.32, 1.20] | 3.00 [0.47, 19.02] |
| NMH | |||||
| Urinary tract infection | 1023 | 1086 | 0.93 [0.86, 1.01] | 0.33 [0.01, 8.19] | 0.93 [0.86, 1.02] |
| Vaginal candidiasis | 1297 | 1359 | 0.95 [0.89, 1.02] | Not applicable | 0.95 [0.89, 1.02] |
| Vaginal infection | 369 | 420 | 0.87 [0.76, 1.00] | Not applicable | 0.87 [0.76, 1.00] |
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
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
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’
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”
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
fRisk ratios were calculated with the random-effects inverse variance method