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CME / ABIM MOC / CE

Does HPV Infection in Pregnant Women Result in Preterm Birth?

  • Authors: MDEdge News Author: Jaleesa Baulkman; CME Author: Laurie Barclay, MD
  • CME / ABIM MOC / CE Released: 10/29/2021
  • THIS ACTIVITY HAS EXPIRED
  • Valid for credit through: 10/29/2022
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Target Audience and Goal Statement

This activity is intended for obstetricians/gynecologists, family medicine/primary care practitioners, nurses, pediatricians, pharmacists and other members of the health care team who treat and manage pregnant women with human papillomavirus infection.

The goal of this activity is to describe the association of human papillomavirus infection during pregnancy with preterm birth, based on the prospective HERITAGE cohort study conducted at 3 academic hospitals in Montreal, Québec, Canada, between November 8, 2010, and October 16, 2016.

Upon completion of this activity, participants will:

  • Assess the association of HPV infection during pregnancy with preterm birth, based on the prospective HERITAGE cohort study
  • Evaluate the clinical and public health implications of the association of HPV infection during pregnancy with preterm birth, based on the prospective HERITAGE cohort study
  • Outline implications for the healthcare team


Disclosures

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Medscape, LLC encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.


MDEdge News Author

  • Jaleesa Baulkman

    Disclosures

    Disclosure: Jaleesa Baulkman has disclosed no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

Editor

  • Stephanie Corder, ND, RN, CHCP

    Associate Director, Accreditation and Compliance
    Medscape, LLC

    Disclosures

    Disclosure: Stephanie Corder, ND, RN, CHCP, has disclosed no relevant financial relationships.

CE Reviewer

  • Esther Nyarko, PharmD

    Director, Accreditation and Compliance
    Medscape, LLC

    Disclosures

    Disclosure: Esther Nyarko, PharmD, has disclosed no relevant financial relationships.

CME Reviewer/Nurse Planner

  • Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP

    Associate Director, Accreditation and Compliance
    Medscape, LLC

    Disclosures

    Disclosure: Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP, has disclosed no relevant financial relationships.

None of the nonfaculty planners for this educational activity have relevant financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.


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CME / ABIM MOC / CE

Does HPV Infection in Pregnant Women Result in Preterm Birth?

Authors: MDEdge News Author: Jaleesa Baulkman; CME Author: Laurie Barclay, MDFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED

CME / ABIM MOC / CE Released: 10/29/2021

Valid for credit through: 10/29/2022

processing....

Clinical Context

Human papillomavirus (HPV) is the most common genital tract viral infection. In Canada, the age group with highest prevalence of HPV infection (15-30 years) overlaps with the age group with highest birth rates (25-34 years).

Study Synopsis and Perspective

Persistent HPV 16 and HPV 18 during a pregnancy may be associated with an increased risk for premature birth.

Findings published online in JAMA Network Open found that 15.9% of individuals who had a persistent HPV 16 or 18 infection during the first and third trimesters of their pregnancy gave birth prematurely compared with 5.6% of those who did not have an HPV infection at all.

The findings prompted the question of "the pathophysiology of HPV in pregnancy and how the virus is affecting the placenta," said Lisette Davidson Tanner, MD, MPH, FACOG, who was not involved in the study.

Researchers said that the findings are the first to show the association between preterm birth and HPV, which is an incurable virus that most sexually active individuals will get at some point in their lives, according to the Centers for Disease Control and Prevention.

"The results of this study are very important in helping us understand the burden caused by HPV in pregnancy," study author Helen Trottier, MSc, PhD, researcher at the Centre Hospitalier Universitaire Sainte-Justine, Montreal, Québec, Canada, said in an interview. "We may have just pinpointed an important cause of preterm birth that has so far been unexplained."

Dr Trottier and colleagues examined data from 1052 pregnant women from 3 university-affiliated health care centers in Montreal between November 8, 2010, and October 16, 2016.

Only 5.6% of those who did not have an HPV infection had a premature birth compared with 6.9% of those who tested positive for any HPV infection in the first trimester.

When looking at the first trimester, researchers found that 12.1% of those diagnosed with HPV 16 and 18 had a preterm birth compared with 4.9% of those who had a high-risk HPV infection other than HPV 16/18. When looking at the third trimester, researchers found that 15.9% of those with HPV 16/18 had an increased risk of giving birth prematurely compared with those who had other high-risk HPV infections.

When researchers looked at the persistence of these HPV infections, they found that most HPV infections detected in the first trimester persist to the third trimester. The findings also revealed that persistent vaginal HPV 16/18 detection was significantly associated with all preterm births and spontaneous preterm births. This association was also found among those who had HPV infections detected in their placentas.

Meanwhile, 5.8% of those who had an HPV infection only during the first trimester experienced a preterm birth.

The researchers also found that HPV infections were frequent in pregnancy even among populations "considered to be at low risk based on sociodemographic and sexual history characteristics," they wrote. Dr Trottier said she hopes the findings will strengthen support for HPV vaccination.

Dr Trottier's study adds to a growing body of research regarding the adverse effects of HPV, according to Dr Tanner, assistant professor of gynecology and obstetrics at Emory University, Atlanta. "It is already well known that HPV is associated with a number of anogenital and oropharyngeal cancers," Dr Tanner said in an interview. "The potential association with preterm birth only adds weight to the recommendations to screen for and prevent HPV infection."

HPV 16 and 18 are high-risk types that cause about 70% of cervical cancers and precancerous cervical lesions, according to the World Health Organization. However, there are 3 HPV vaccines--9-valent HPV vaccine, quadrivalent HPV vaccine, and bivalent HPV vaccine--that help protect against HPV 16/18.

The findings strengthen the benefits of HPV vaccination, Dr Trottier explained. "There is no cure when the HPV infection is present," Dr Trottier said. "If the link [between preterm birth and HPV infections] is indeed causal, we can expect a greater risk of preterm delivery in these women. The effective tool we have is the HPV vaccination, but it should ideally be received before the start of sexual activity in order to prevent future infections that could occur in women."

The American College of Obstetricians and Gynecologists recommends HPV vaccination for girls and women between the ages of 11 and 26 years. However, Dr Tanner said, women aged 27 to 45 years who were previously unvaccinated may still receive benefit from the vaccine.

"Despite the known efficacy of the vaccine, only 50% of patients are up to date with their HPV vaccination," Dr Tanner explained. "This study further highlights the need to educate and encourage patients to be vaccinated."

The researchers said that future studies should investigate the association of HPV vaccination and vaccination programs with the risk for preterm birth.

The experts disclosed no conflicts of interest.

JAMA Netw Open. 2021;4(9):e2125308.

Study Highlights

  • The prospective HERITAGE cohort study was conducted at 3 academic hospitals in Montreal.
  • Between November 8, 2010, and October 16, 2016, 899 women with singleton pregnancies were recruited and tested for vaginal HPV DNA detection in the first and third trimesters, as well as for placental HPV infection.
  • Mean age was 31.3±4.6 years (range, 19-47 years).
  • Follow-up was completed June 15, 2017.
  • The primary outcome was preterm birth (live birth or stillbirth between 20 weeks, 0 days, and 36 weeks, 6 days, of gestation).
  • HPV DNA was detected in vaginal samples in 378 women (42.0%) during the first trimester and in 91 (11.1%) of 819 placentas at delivery.
  • HPV detection in biopsy specimens and under the amniotic membrane suggest that these were true placental infections rather than placental contamination during delivery.
  • 55 women had preterm birth (38 spontaneous; 17 medically indicated).
  • Preterm birth occurred in 15.9% of women with persistent HPV 16 or 18 infection during the first and third pregnancy trimesters, in 6.9% of those with any HPV infection in the first trimester, and in 5.6% of those not infected with HPV.
  • Preterm birth occurred in 12.1% of those with HPV 16 and 18 and in 4.9% of those with other high-risk HPV infection during the first trimester.
  • Overall, 5.8% of those with HPV infection only during the first trimester had preterm birth.
  • Most HPV infections detected in the first trimester persisted to the third trimester.
  • On logistic regression, persistent vaginal HPV-16/18 detection was significantly associated with all preterm births (adjusted odds ratio [aOR], 3.72; 95% confidence interval [CI], 1.47-9.39) and spontaneous preterm births (aOR, 3.32; 95% CI, 1.13-9.80).
  • Placental HPV infection was significantly associated with all preterm births (aOR, 2.53; 95% CI, 1.06-6.03) and spontaneous preterm births (aOR, 2.92; 95% CI, 1.09-7.81).
  • Restricting the analysis to participants without history of cervical intraepithelial neoplasia treatment yielded similar results.
  • Vaginal HPV detection of any genotype in the first pregnancy trimester was not associated with preterm birth.
  • The investigators concluded that HPV infection is frequent in pregnancy even in a population thought to be low-risk based on sociodemographics and sexual history, and that most HPV infections detected in the first trimester persist to the third trimester.
  • In addition, persistent HPV-16/18 infection is associated with increased risk for preterm birth, above infections by other HPV genotypes, and independent of cervical treatment.
  • Low prevalence of cervical treatment makes it unlikely to explain the association between HPV and preterm birth, and excluding women with a history of treatment did not change the conclusions.
  • HPV infection may be associated with vaginal microbiota changes, which might trigger an immuno-inflammatory process leading to preterm birth, but further research is needed.
  • If confirmed in larger, more diverse populations, these findings would support a role for HPV vaccination programs to lower the burden of preterm births.
  • This positive association would likely occur during the next decade at the population level in settings with high-coverage HPV vaccination programs, when cohorts of girls vaccinated before sexual debut reach childbearing age.
  • ACOG recommends HPV vaccination for girls and women aged 11 to 26 years, but previously unvaccinated women aged 27 to 45 years may also benefit.
  • However, only 50% of eligible patients are up to date with HPV vaccination, highlighting the need to educate patients and encourage vaccination.
  • The investigators recommend that future research investigate the association of HPV vaccination and vaccination programs with risk for preterm birth.
  • Study limitations include possible residual confounding, inability to determine whether HPV infection conferred higher risk for preterm birth in women with elevated baseline risk, and possible placental contamination during birth.
  • The conclusions may also not be generalizable to higher-risk populations.

Clinical Implications

  • In a large, multicenter, cohort study, persistent HPV-16/18 infection during pregnancy was significantly associated with preterm birth.
  • If that association is causal, HPV vaccination may reduce preterm birth and the associated burden.
  • Implications for the Health Care Team: Only 50% of eligible patients are up to date with HPV vaccination, highlighting the need to educate patients and encourage vaccination.

 

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