With the increasing prevalence of human papillomavirus (HPV) infection in the population, the issue of delivery methods for pregnant women with co-infection with HPV is gradually attracting the attention of medical practitioners. The mode and mechanism of transmission of HPV infection are still not well understood, and there is a lack of clinical trial results and expert consensus-based recommendations for treatment in large samples internationally, which has caused many problems for clinicians and patients.
Many pregnant women wonder whether HPV infection in pregnancy can be delivered via vaginal delivery, and whether cesarean section can effectively prevent mother-to-child transmission. With these questions, we first need to understand the characteristics of HPV infection during pregnancy, the route of HPV transmission between mother and child, and the impact of HPV infection on the prognosis of the newborn.
1. Characteristics of HPV infection during pregnancy
Investigations on the incidence of HPV co-infection during pregnancy have shown widely varying results. According to a meta-data published in 2013, the incidence ranged from 6 to 65%, with an average of 24%. HPV is divided into two categories, low-risk HPV and high-risk HPV, according to the level of viral oncogenicity. It is currently believed that the susceptibility to HPV is increased due to the occurrence of a series of physiological changes in the body after pregnancy, which acts as an independent factor.
The physiological changes that occur in the body after pregnancy include.
(1) Changes in immune status: To avoid maternal immune rejection of the fetus, the placenta secretes large amounts of such hormones as human chorionic gonadotropin (hCG), human placental prolactin (hPL), estrogen and progesterone, as well as increased secretion of adrenaline in the body. These hormones suppress the immune response in the body and also promote the production of large amounts of suppressors in the plasma to inhibit lymphocyte transformation. The fetus also produces a variety of carcinoembryonic antigens such as methemoglobin during development, which can also suppress the maternal immune response. As a result, the mother is in a state of immune tolerance or immune non-response during pregnancy. The body’s immunity is low, the ability to fight the virus is reduced, and HPV replication is active, resulting in a higher rate of maternal infection than during non-pregnancy. If there are other obstetric comorbidities (such as gestational diabetes), the infection rate will increase further.
(2) Increased secretion of estrogen, progesterone and gonadotropin during pregnancy can increase the transcriptional activity of HPV non-coding and increase HPV susceptibility.
(3) Pelvic congestion, abundant blood supply to the reproductive system, increased vaginal secretions and humid environment during pregnancy are all extremely favorable conditions that can promote HPV invasion and proliferation.
2. HPV transmission mechanism from mother to child
It is currently believed that HPV transmission between mothers and infants can occur vertically and horizontally.
(1) Vertical transmission between mothers and infants can be caused by intrauterine infection of the fetus through amniotic fluid, placenta and umbilical cord blood, or transmission through the birth canal during delivery. In studies of HPV-infected pregnant women, HPVDNA was detected in fetal appendages, or in the penile foreskin and oral cavity of fetuses delivered by cesarean section, and its consistency with the type of HPV infection in pregnant women confirmed the presence of intrauterine infection. An additional route of vertical transmission is through contact of the newborn with the HPV-infected cervix or vagina during delivery.
(2) HPV can be transmitted horizontally from mother to child through breastfeeding, or through daily contact. Although the incidence of transmission is low, it needs to be taken seriously as a mode of transmission, and further studies should include newborn contact groups, such as parents and siblings, in the study.
3. Impact of HPV infection on mother and child
(1) Effects on pregnant women: Since pregnancy can be an independent factor affecting HPV infection, most pregnant women show high levels of asymptomatic HPV infection. Women with HPV infection are more likely to have combined condyloma acuminatum or cervical intraepithelial neoplasia (CIN) after pregnancy. Compared to non-pregnant women, warts during pregnancy are more numerous, larger, and grow more rapidly, and may even develop into Buschkel
Oewenstein tumors (giant tumors). Sometimes warts can cover the vagina and perineum, resulting in heavy local bleeding during transvaginal delivery and even soft birth canal lacerations. Also warts tend to break down, further increasing the rate of genital infection. It has also been suggested that HPV infection may be associated with the occurrence of premature rupture of membranes.
(2) Impact of HPV infection on fetal and neonatal prognosis: Pregnancy combined with HPV infection may lead to miscarriage and preterm delivery, and there is no definite conclusion as to whether it increases the incidence of fetal malformation and intrauterine distress.
Current studies suggest that most HPV infections in neonates are from vertical transmission between mothers and infants (especially type 6/11). Some scholars have dynamically monitored HPV infections in pharyngeal secretions of neonates at birth, 48-72 hours after birth, and 6 weeks after birth, and found that pharyngeal HPV infections showed a decreasing trend as time lengthened, and HPV infections in neonates often spontaneously turned negative 6 months after birth.
Clinically uncommon HPV-associated skin and mucosal lesions in infants and children manifest as congenital condyloma acuminata in the anal and genital areas, conjunctival papilloma, and laryngeal papillomatosis. The incidence of neonatal whistle tract papillomatosis is approximately 0.7%, with a high mortality rate. Whistler’s papillomatosis can also develop in adolescence and manifests as scattered corn-like or polypoid or cauliflower-like growths in the pharynx, causing hoarseness and inspiratory difficulties, and is characterized by easy recurrence and difficulty in eradication. In the clinic, for non-sexual adolescents infected with genital warts, or recurrent inhalation papillomatosis, should be highly suspicious of congenital HPV infection may.
4. Choice of delivery method for HPV-infected patients
In a meta-analysis published by K. Chatzistamatiou et al. in 2015, the rate of neonatal HPV infection after cesarean section and transvaginal delivery was 15% and 28%, respectively, in women with co-infection with HPV. Combining the results of existing studies.
(1) cesarean section only avoids the occurrence of vertical transmission of HPV between mothers and infants through the birth canal, and there are other transmission routes such as horizontal transmission between mothers and infants and breastfeeding after delivery, and there is still about 15% infection rate in newborns after cesarean section, which does not fully achieve the effect of protecting the offspring.
(2) HPV infection in newborns has a good prognosis, often spontaneously turning negative 6 months after birth, and persistent HPV infection rarely occurs.
(3) The occurrence of serious complications such as neonatal and adolescent whistling papillomatosis is extremely rare.
Therefore, women with co-infection with HPV can deliver via vaginal delivery, and cesarean section is not effective in preventing transmission from mother to child. Cesarean section is preferred only when large genital warts prevent vaginal delivery or may cause severe bleeding or genital tract injury. However, active clinical campaigns should still be conducted to reduce the rate of HPV infection during pregnancy and, in turn, to reduce the rate of infection in the newborn.