Is HPV vaccination in pregnancy safe?

Figures & data

Figure 1. Flow Chart of the Systematic Literature Search.

Table 1. The 5 major studies included in the present review. *PATRICIA: PApilloma TRIal against Cancer In young Adults. #CVT: The Costa Rica Vaccine Trial. HAV: Hepatitis A-vaccine. HPV: HPV vaccine. VAERS: Vaccine Adverse Event Reporting System. LMP: Last menstrual period.

Authors	Year	Country	Studies included	No. of pregnant HPV-vaccinees	No. of pregnant placebo or control vaccine recipients	Inclusion criteria	Follow up period	Main outcome measure
Wacholder et al.^16	2010	Costa Rica	Pooled analysis of two multicentre, phase three masked RCT's, Cervarix. (PATRICIA* and CVT#)	2346/13,075	2364/13,055 HAV	Age 15–25 (PATRICIA*) and 18–25 (CVT#)	N/A	Spontaneous abortion < 20 weeks of gestation
Panagiotou et al.^17	2015	Costa Rica	Blinded RCT (Cervarix).Long term follow up on the study of Wacholder et al.	2279/3727	3739 HAV and 2836 no vaccine	18–25 years, Conception < 90 days of vaccination	4 years (+ 6 years)	Spontaneous abortion < 20 weeks of gestation
Garland et al.^18	2009	Australia	5 phase III trials (Gardasil) (013, 015, 016, 018, 019)	1796	1824		0.6–3.7 years	Live births, fetal loss, fetal outcome, ectopic pregnancy
Dana et al.^19	2009	USA	Original study (Gardasil)	517 prospective reports	None	Exposure 1 month before LMP or at any time during pregnancy	2 years after birth through pediatric reports	Pregnancy outcomes, birth defects
Angelo et al.^20	2014	Belgium/USA	42 ongoing or completed controlled and uncontrolled blinded studies (Cervarix)	465	449	HPV-vaccine during pregnancy, i.e. 60 days before onset of pregnancy (LMP+14 days) up until the end of pregnancy	8.4 years post-vaccination	Elective termination, spontaneous abortion, stillbirth, preterm birth, term birth, postmature birth

Table 2. Overview of data on spontaneous abortions. NA: Not applicable because of no control/unvaccinated group. RR: Relative risk (HPV over Control). 95% CI: exact 95% confidence interval for relative risk.

Authors	Coutry / Year	Vaccine	Sp. abortions in pregnancies included in analysis, HPV No. (%)	Sp.abortions in pregnancies included in analysis, HAV No. (%)	Sp. abortions in pregnancies included in analysis, placebo No.(%)	P value / RR
Wacholder et al.^16	Costa Rica / 2010	Cervarix™	197/1708 (11.5%)	176/1727 (10.2%)	NA	P = 0.16
Panagiotou et al.^17	Costa Rica / 2015	Cervarix™	451/3394 (13.3%)	*316/2507 (12.6%)	**98/720 (13.6%)	*RR 1.05 (0.91–1.21) **RR 0.95 (0.77–1.18)
Garland et al.^18	Australia /2009	Gardasil®	366/2008 (18.2%)	395/2029 (19.5%)	NA	P = 0.96
Dana et al.^19	USA / 2009	Gardasil®	34/517 (6.6%)	NA	NA	NA
Angelo et al.^20	Belgium/USA / 2014	Cervarix™	71/465 (15.3%)	NA	50/449 (11.1%)	RR 1.37 (95% CI 0.94–2.01)

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Panagiotou OA, Befano BL, Gonzalez P, Rodriguez AC, Herrero R, Schiller JT, Kreimer AR, Schiffman M, Hildesheim A, Wilcox AJ, et al. Effect of bivalent human papillomavirus vaccination on pregnancy outcomes: long term observational follow-up in the Costa Rica HPV Vaccine Trial. BMJ 2015; 351:h4358; PMID:26346155; http://dx.doi.org/10.1136/bmj.h4358

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Garland SM, Ault KA, Gall SA, Paavonen J, Sings HL, Ciprero KL, Saah A, Marino D, Ryan D, Radley D, et al. Pregnancy and infant outcomes in the clinical trials of a human papillomavirus type 6/11/16/18 vaccine: a combined analysis of five randomized controlled trials. Obstet Gynecol 2009; 114:1179-88; PMID:19935017; http://dx.doi.org/10.1097/AOG.0b013e3181c2ca21

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Dana A, Buchanan KM, Goss MA, Seminack MM, Shields KE, Korn S, Cunningham ML, Haupt RM. Pregnancy outcomes from the pregnancy registry of a human papillomavirus type 6/11/16/18 vaccine. Obstet Gynecol 2009; 114:1170-8; PMID:19935016; http://dx.doi.org/10.1097/AOG.0b013e3181c2a122

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Angelo MG, David MP, Zima J, Baril L, Dubin G, Arellano F, Struyf F. Pooled analysis of large and long-term safety data from the human papillomavirus-16/18-AS04-adjuvanted vaccine clinical trial programme. Pharmacoepidemiol Drug Saf 2014; 23:466-79; PMID:24644063; http://dx.doi.org/10.1002/pds.3554

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