SAN FRANCISCO – Women found to be infected with high-risk types of human papillomavirus early in pregnancy are more than twice as likely to develop preeclampsia, according to a retrospective cohort study reported at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.
"This study supports an association between high-risk human papillomavirus and preeclampsia, which is consistent with the association that was previously seen between high-risk HPV and cardiovascular disease," lead investigator Dr. Mollie McDonnold commented.
Dr. Mollie McDonnold
"If this is confirmed in future prospective studies or larger cohorts, it may suggest a potential role for HPV vaccination in preeclampsia prevention," she added.
Using study data and data on the population prevalence of high-risk HPV infection, the investigators estimated that if all women received the quadrivalent vaccine (which prevents about two-thirds of such infections), the rate of preeclampsia would fall from 5,189 to 5,020 cases per 100,000 women.
"When you are doing a preeclampsia study like this, the clinical diagnosis in multiparas has a high degree of uncertainty. So did you look separately at your nulliparas?" one attendee asked.
"In order to achieve numbers, we did include nulliparous and multiparous women in our study. We haven’t looked specifically at this, but in our regression model, we did control for nulliparity. We could certainly, hopefully with more numbers, look exclusively at nulliparas," replied Dr. McDonnold, who is an obstetrician-gynecologist at the University of Texas Medical Branch in Galveston.
Another attendee noted that Pap test results were often used as a surrogate for HPV status. "Could you separate out the effect of HPV status from the effect of Pap status – the difference between the groups could not only be HPV driven but also Pap driven?" he wondered.
Women did not necessarily have HPV testing unless it was clinically indicated, Dr. McDonnold acknowledged. And some classified as noninfected may have had HPV infection. "The reason why we asked to have two normal Pap smears was to increase the sensitivity and specificity of the Pap smear of being negative for HPV. But certainly you could say that this was Pap smear data only."
Giving some study background, she noted that high-risk HPV has been previously implicated in both adverse pregnancy outcomes and adverse cardiovascular outcomes.
"This association between HPV and cardiovascular disease is relevant in pregnancy, as preeclampsia and cardiovascular disease share a similar pathophysiology," including endothelial dysfunction and inflammation, as well as vascular risk factors such as obesity, hypertension, diabetes, and dyslipidemia, Dr. McDonnold elaborated.
High-risk HPV transfects trophoblasts, causing changes that interfere with normal placentation, and also disables tumor suppressor proteins, accelerating unfavorable vascular changes typically seen in atherosclerosis.
"So we believe there is a biologic plausibility to support a role of high-risk HPV and preeclampsia," Dr. McDonnold said.
For the study, the investigators classified women as having high-risk HPV if they had atypical squamous cells of undetermined significance (ASCUS) plus detection of a high-risk type on reflex DNA testing, or if they had a cervical pathology known to be associated with this infection. A total of 314 pregnant women were classified as having high-risk HPV.
The investigators matched each infected woman by delivery date with two noninfected women who had negative Pap test results both before and during the pregnancy.
The groups were similar with respect to obstetric risk factors such as chronic hypertension and twin gestations, according to Dr. McDonnold.
Women infected with high-risk HPV had a higher rate of preeclampsia than their noninfected counterparts did (10.2% vs. 4.9%, P = .004). They also tended to have a higher rate of severe preeclampsia (5.1% vs. 2.7%, P = .09).
After adjustment for age, nulliparity, blood pressure at entry to care, and smoking, the difference corresponded to a more than doubling of the odds of preeclampsia for the high-risk HPV group (odds ratio, 2.29), according to data reported at the meeting.
The women with high-risk HPV also were significantly more likely to have a spontaneous preterm birth before 37 weeks (OR 1.83), any preterm birth before 35 weeks (2.58), and spontaneous preterm birth before 35 weeks (6.85).
However, the two groups were statistically indistinguishable with respect to the outcomes of gestational hypertension, gestational diabetes, intrauterine growth restriction, and cesarean delivery.
Dr. McDonnold disclosed no relevant conflicts of interest.