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

Jørgensen, Lars; Gøtzsche, Peter C.; Jefferson, Tom

doi:10.1186/s13643-019-0983-y

Systematic Reviews

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 diseases^a	HPV vaccine total (N = 47,075)	Comparator total (N = 48,595)	Risk ratio^f total [95% CI]	Risk ratio^f MSC [95% CI]	Risk ratio^f NMH [95% CI]
Total
Participants with new onset diseases^b	14,258	14,014	0.99 [0.97, 1.02]	0.98 [0.90, 1.06]	1.00 [0.97, 1.03]
Follow-up^c	2296	2365	0.98 [0.94, 1.01]	Not applicable	0.98 [0.94, 1.01]
Number of MedDRA-classified new onset diseases^b	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

Back to article page

ISSN: 2046-4053

Contact us

Submission enquiries: Access here and click Contact Us
General enquiries: info@biomedcentral.com