Effect of bivalent human papillomavirus vaccination on pregnancy outcomes: long term observational follow-up in the Costa Rica HPV Vaccine Trial

Abstract

ObjeCtiveTo examine the effect of the bivalent human papillomavirus (HPV) vaccine on miscarriage. DesignObservational long term follow-up of a randomized, double blinded trial combined with an independent unvaccinated population based cohort.setting Single center study in Costa Rica.PartiCiPants 7466 women in the trial and 2836 women in the unvaccinated cohort enrolled at the end of the randomized trial and in parallel with the observational trial component.interventiOn Women in the trial were assigned to receive three doses of bivalent HPV vaccine (n=3727) or the control hepatitis A vaccine (n=3739). Crossover bivalent HPV vaccination occurred in the hepatitis A vaccine arm at the end of the trial. Women in the unvaccinated cohort received (n=2836) no vaccination. Main OutCOMe MeasureRisk of miscarriage, defined by the US Centers for Disease Control and Prevention as fetal loss within 20 weeks of gestation, in pregnancies exposed to bivalent HPV vaccination in less than 90 days and any time from vaccination compared with pregnancies exposed to hepatitis A vaccine and pregnancies in the unvaccinated cohort. resultsOf 3394 pregnancies conceived at any time since bivalent HPV vaccination, 381 pregnancies were conceived less than 90 days from vaccination. Unexposed pregnancies comprised 2507 pregnancies conceived after hepatitis A vaccination and 720 conceived in the unvaccinated cohort. Miscarriages occurred in 451 (13.3%) of all exposed pregnancies, in 50 (13.1%) of the pregnancies conceived less than 90 days from bivalent HPV vaccination, and in 414 (12.8%) of the unexposed pregnancies, of which 316 (12.6%) were in the hepatitis A vaccine group and 98 (13.6%) in the unvaccinated cohort. The relative risk of miscarriage for pregnancies conceived less than 90 days from vaccination compared with all unexposed pregnancies was 1.02 (95% confidence interval 0.78 to 1.34, one sided P=0.436) in unadjusted analyses.

Is HPV vaccination in pregnancy safe?

“…The abstracts of the 45 remaining citations were read and 18 were excluded as not being relevant. Of the remaining 27 citations the full manuscript was examined and 5 [16][17][18][19][20] were chosen as relevant for the review (Table 1). Our aim was to provide an overview of the safety of HPV vaccination in pregnancy or immediately pre-conceptually.…”

“…[16][17][18][19][20] A total of 1,119 miscarriages occurred in the 8,092 pregnancies exposed to the HPV vaccine giving a miscarriage rate ranging from 6.6% 19 to 18.2%. 18 In 4 of the studies, [16][17][18]20 the exposed pregnancies were compared to either Hepatitis A vaccine (HAV) exposed [16][17][18] or placebo exposed pregnancies 20 and one study included both an HAV group and a placebo group. 17 None of the studies found a significantly increased rate of spontaneous abortion in the overall analyses.…”

“…18 In 4 of the studies, [16][17][18]20 the exposed pregnancies were compared to either Hepatitis A vaccine (HAV) exposed [16][17][18] or placebo exposed pregnancies 20 and one study included both an HAV group and a placebo group. 17 None of the studies found a significantly increased rate of spontaneous abortion in the overall analyses. Looking at subgroups (e.g., age, interval of estimated time of conception and nearest vaccination, number of vaccinations) one study 16 detected a significant increase in the risk of miscarriage (14.7% vs. 9.2%, P D 0.031).…”

HPV vaccination and pregnancy

“…h4358) report on the long term follow-up for pregnancy outcomes in women enrolled in the Costa Rica HPV Vaccine Trial. 2 An earlier pooled analysis from this trial and the PApilloma TRIal against Cancer In young Adults (PATRICIA) trial found no overall association between vaccination using the bivalent vaccine and spontaneous abortion, but a small increase in risk in the subgroup of pregnancies conceived within 90 days of vaccination could not be completely ruled out. 3 In the Costa Rica trial, women were randomised to the bivalent HPV vaccine or control hepatitis A vaccine, with four years of follow-up, and crossover vaccination was offered before a four year post-intervention period.…”

Epidemiologie, Prävention und Früherkennung des Zervixkarzinoms

“…Der Impfschutz gegen Neuinfektionen mit HPV16 oder HPV18 ist höher als 90% in Frauen, die zum Zeitpunkt der Impfung keine HPV16/18 Infektion haben. Die HPV-Impfung wird in der Regel sehr gut toleriert und hat kaum Nebenwirkungen (14). Gegen bestehende Infektionen oder Krebsvorstufen konnte keine überzeugende Wirksamkeit der Impfstoffe gezeigt werden (15).…”