By Philip R. Fischer, MD, DTM&H
Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN; Department of Pediatrics, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates
SYNOPSIS: Nearly half of pregnant women in a Canadian study had vaginal swabs positive for human papillomavirus (HPV) deoxyribonucleic acid (DNA). Only about one-fourth of placentas and newborns produced by those HPV-positive women carried detectable HPV DNA, and all HPV-positive babies had cleared their positivity by 6 months of age.
SOURCE: Khayargoli P, Niyibizi J, Mayrand MH, et al; HERITAGE Study Group. Human papillomavirus transmission and persistence in pregnant women and neonates. JAMA Pediatr 2023; May 22. doi: 10.1001/jamapediatrics.2023.1283. [Online ahead of print].
Realizing that the prevalence of intra-partum human papillomavirus (HPV) infection is not well known and that the risk of mother-to-child transmission of HPV is not well studied, a research team in Montreal, Canada, prospectively studied 1,050 women and their offspring from the first trimester of pregnancy through six months post-delivery from 2010 through 2016 at three academic medical centers. Vaginal, placental, and infant samples were tested for HPV deoxyribonucleic acid (DNA).
At study enrollment, the mean age of participating pregnant women was 31 years. Overall, 71% of participants identified as white. The median number of years of education was 17 (i.e., most had completed college/university studies). They reported a median age of first sexual encounter of 17 years; 26% had had one or two lifetime sexual partners, and 25% had had three to five lifetime sexual partners. During the preceding 12 months, 92% of study participants had had no new sexual partners. Overall, 85% had not received even one dose of HPV vaccine.
When first tested, 40% of women were HPV-positive. Of those, 45% had multiple HPV genotypes identified (with eight different genotypes reported in a single patient), and 66% had at least one high-risk genotype. HPV was identified on 11% of placentas but only from under the amniotic membrane on the fetal side of 4%. HPV was identified in 7% of babies at birth and/or 3 months of age, with positive swabs identified from conjunctivae, mouth, genitals, and pharynx (in decreasing order of frequency). All infants who tested positive at birth or 3 months of age tested negative at 6 months of age.
This research group previously had reported on serology results in 58 of these mother-baby pairs in whom the mother had been HPV-positive by vaginal swab. Maternal and neonatal HPV immunoglobulin G (IgG) levels were strongly correlated, but by 12 months of age, 80% of previously seropositive newborns had become HPV IgG-negative, and by 24 months of age, all previously seropositive children were HPV IgG-negative.1
While HPV infection was common in pregnant women, the authors found minimal evidence for transmission of actual infection to newborns (even though placental swabs were sometimes positive, and HPV was transiently detected on the bodies of some infants). However, evaluation of subsequent results at 5 years of age will be important since it is possible that some babies became swab-negative while harboring dormant HPV in basal cells where infection might reactivate at a later time.
COMMENTARY
Women were enrolled in this study from 2010 through 2016, just a few years after 2006 when Canada started offering a quadrivalent HPV vaccine for 9- to 26-year-olds.2 Thus, many of the women who enrolled in this study were potentially infected with HPV before they would have had access to even the initial vaccines. Indeed, the vast majority of women were unvaccinated, and the prevalence of HPV in vaginal secretions was 40%. Thus, this study provides a “natural experiment” of maternal-to-child transmission of HPV.
Clearly, babies were exposed to vaginal HPV during the birth process, and 6% had positive skin or mucosal swabs at birth, with 3% positive at 3 months of age. Whether an actual infection was established in the newborns is less clear, and all of these previously HPV-positive babies tested negative at 6 months of age. Ongoing studies will help reveal if some of these exposed children might actually have become infected and are at risk of future reactivation of infection and even the development of HPV-related tumors.
In the United States, the Centers for Disease Control and Prevention (CDC) currently suggests that HPV vaccine be given routinely at 11-12 years of age and that unvaccinated individuals up to 26 years of age be vaccinated.3 Between ages 27 and 45 years, HPV vaccination could be considered if there is concern for new exposure, such as prior to contact with a new sexual partner.3 HPV vaccination protects against infection but not against sequelae of a previously established infection.3
In the Montreal study, 94% of women had had a normal cervical cytology study, but 1% had had squamous intraepithelial lesions on their most recent cytology tests. There usually is a decade or two between the initial HPV infection and the development of cancer.4 Thus, regular screening can identify women with precancerous lesions so that effective treatment can prevent life-threatening cancer from being established.4 Newer self-sampling methods have allowed for effective screening without the discomfort of a medical visit and a pelvic exam.4
There are approximately 13 million new cases of HPV infection in the United States each year, yet vaccines are 96% effective in preventing precancerous lesions.5 A recent meta-analysis confirms that HPV vaccination around the time of conception or during pregnancy is not associated with any adverse outcomes of pregnancy.6
The study population in this new study from Montreal was mostly white, was highly educated, and had access to academic health centers. This suggests that these women were at least representative of some of the patients for whom we care. And perhaps their baseline data at enrollment in the study can help debunk some common perceptions. First, a common belief is that “all adolescents have sex.” However, half of the women in this study did not have their first sexual encounter until age 17 years or later. Second, there is a perception that “everyone knows about ‘safe sex.’” Clearly, the high rate of vaginal secretions that were positive for HPV of many different genotypes makes it clear that unprotected sexual intercourse is common; even if some people “know about safe sex,” protective measures are not always implemented. Of course, reserving sexual intercourse for monogamous relationships and, in other cases, using barrier protection should protect against most if not all HPV infections. Encouragingly, the CDC says that “people who are in a long-term, mutually monogamous relationship are not likely to get a new HPV infection.”3 Completing an HPV pre-exposure vaccination series remains effective for those who practice riskier behaviors.
REFERENCES
- Zahreddine M, Mayrand MH, Therrien C, et al. Antibodies to human papillomavirus types 6, 11, 16 and 18: Vertical transmission and clearance in children up to two years of age. EClinicalMedicine 2020;21:100334.
- National Advisory Committee on Immunization. An Advisory Committee Statement: Update on human papillomavirus (HPV) vaccines. The Public Health Agency of Canada. 2012;38:ACS-1. https://www.canada.ca/en/public-health/services/reports-publications/canada-communicable-disease-report-ccdr/monthly-issue/2012-38/canada-communicable-disease-report.html
- Centers for Disease Control and Prevention. HPV Vaccination Recommendations. Last reviewed Nov. 16, 2021. https://www.cdc.gov/vaccines/vpd/hpv/hcp/recommendations.html
- Di Gennaro G, Licata F, Trovato A, Bianco A. Does self-sampling for human papilloma virus testing have the potential to increase cervical cancer screening? An updated meta-analysis of observational studies and randomized clinical trials. Front Public Health 2022;10:1003461.
- Markowitz LE, Unger ER. Human papillomavirus vaccination. N Engl J Med 2023;388:1790-1798.
- Yan X, Li H, Song B, et al. Association of periconceptional or pregnancy exposure of HPV vaccination and adverse pregnancy outcomes: A systematic review and meta-analysis with trial sequential analysis. Front Pharmacol 2023;14:1181919.
