Introduction 

The human papilloma virus (HPV), a member of the Papovaviridae family, is a double stranded DNA virus with more than 60 subtypes identified; 20 of these subtypes affect the epithelium of the genital tract. Condylomata acuminata (subtypes 6 and 11) and cervical dysplasia (subtypes 16, 18, 31, 33 and 35) are the most common clinical manifestations of HPV infections. With respect to pregnancy, the increased prevalence, potential for precluding safe vaginal delivery, and possible maternal-fetal transmission of HPV are reviewed in this issue of Clinical Discussions.

Prevalence and Treatment

HPV disease is common, with approximately 20% of the population affected with overt lesions. Polymerase chain reaction (PCR) analysis has identified HPV DNA in as many as 60% of sexually active females. The incidence of HPV infections appears to have increased some 10-fold over the past 10 years in both private offices and sexually transmitted disease (STD) clinics, although improved detection rather than actual increase in infection rate has been postulated by some experts. Genital warts, condylomata acuminata, are thought to be sexually transmitted, although other direct person-to-person contact may result in inoculation. The incubation period from exposure to overt infection ranges from 3 weeks to 8 months, and the infection rate from exposure is approximately 60%. Recurrence following treatment is common, and more often results from reactivation of virus than from reinfection by sexual partners.

Schneider et al found HPV-DNA in 28% of cytologically normal pregnant women and in only 12.5% of nonpregnant controls. The rate of HPV DNA detection increased from 9% in the first trimester of pregnancy to 28% in the second, and 33% in the third trimester. Infected pregnant women also had greater amounts of HPV DNA in their cells. HPV growth is stimulated by estrogen and glucocorticoids. Furthermore, the T-helper to T-suppressor ratio decreases with gestational age; temporary depression of cell-mediated immunity is thought to account for the increased prevalence of HPV during pregnancy.

There are several treatment modalities available during pregnancy. Application of 50-90% trichloroacetic acid (TCA), cryotherapy with liquid nitrogen or cryoprobe, electrocautery, and CO₂ laser are considered safe, and variably effective, during pregnancy, whereas podophyllin, 5-FU, bleomycin, and interferon are contraindicated during pregnancy. Treatment is not curative: success rates of 22-94%, and a recurrence rate of approximately 25%, have been reported with the various modalities in the nonpregnant state. Spontaneous regression is also common, especially postpartum. However, there is no proof that treatment (debulking) or spontaneous regression reduces sexual or maternal-fetal transmission of HPV as potentially infectious virus remains in the tissue after exophytic lesions resolve.

Labor and Delivery

Juvenile Laryngeal Pappilomatosis 

In 1871, MacKenzie noted the frequent association of skin warts and laryngeal papillomas. Two forms of laryngeal papillomas have been described. An adult form, nonaggressive and with solitary lesions and a male predilection, is often cured following a single operative procedure. Juvenile laryngeal papillomatosis (JLP), also called recurrent respiratory papillomatosis, on the other hand, is extremely aggressive and resistant to treatment, usually surgical. It typically involves the trachea, but may spread to the esophagus and bronchi, and rarely, to the lung where it actually destroys tissue, dramatically worsening the prognosis. Although rare, it is the most common benign tumor of the larynx.

The incidence of JLP has been reported as 1:1500 live births. Because of its rarity, together with the relatively high prevalence of genital HPV, there has been some doubt about the cause of JLP. However, subtypes 6 and 11 of the HPV virus have been isolated from nearly all JLP lesions tested, and many experts believe that maternal-fetal transmission, is responsible for the lesions. Indeed, several retrospective studies have supported this mechanism of infection, with majorities of affected children born to mothers with documented HPV infection during pregnancy. One investigator found HPV DNA in nasotracheal aspirates of 48% of infants born to mothers with condylomata acuminata at the time of delivery. Prospective studies, however, have not been as supportive of maternal-fetal transmission. Among 44,000 infants followed for 7 years as part of the Collaborative Perinatal Project, none were found to have JLP. Another study, which found, retrospectively, that 5/9 infants with JLP were born to mothers with condylomata acuminata, found, prospectively, no cases of JLP in 31 infants born to women with overt HPV infection. Proponents of maternal-fetal transmission point out that the long latency period of 5 years or more for overt HPV infection of the larynx, and the small number of mother/infant pairs in the latter study, precluded any conclusion about the mechanism of infection in such a rare disease.

Cesarean delivery has been proposed as a potential means of preventing JLP. However, although cesarean delivery is rare among infants and children with JLP, HPV DNA has been found in amniotic fluid before rupture of the fetal membranes and in oropharyngeal swabs of infants born by cesarean section. It is also unclear whether, as with genital HSV, recurrent lesions are less likely than primary ones to result in maternal-fetal transmission. The protective potential to the fetus/neonate of cesarean delivery probably does not exceed its potential morbidity to the mother. Most experts, including the CDC in its most recent treatment guidelines of STD's, recommend cesarean delivery only for the usual obstetric and fetal indications, and for those with extensive lesions precluding a safe vaginal delivery for the mother.

Of course, there are the medicolegal concerns regarding the association of maternal HPV and JLP. In fact, there has been a recent case favoring the mother of a child with JLP who alleged that her obstetrician did not adequately explain this very association to her. The rarity of JLP and its long incubation period have made it difficult for obstetricians to appreciate this manifestation of perinatal HPV. For those interested, information for parents of children with JLP can be obtained from the Recurrent Respiratory Papillomatosis Foundation, 50 Wesleyan Drive, Hamilton Square, NJ, 08690.

1. Osborne NG, Adelson MD. Herpes simplex and human papillomavirus genital infections: controversy over obstetric management. Clin Obstet Gynecol 33(4):801,1990.
   
2. Sexually Transmitted Diseases Treatment Guidelines. MMWR 42(RR-14):83,1993.
   
3. Cripe TP. Human papilloma viruses: pediatric perspectives on a family of multifaceted tumorigenic pathogens. Pediatr Infect Dis J 9(11):836,1990.
   
4. Shah K, Kashima H, Polk BF, et al. Rarity of cesarean delivery in cases of juvenile-onset respiratory papillomatosis. Obstet Gynecol 68(6):795,1986.
   
5. Hallden C, Majmudar B. The relationship between juvenile laryngeal papillomatosis and maternal condylomata acuminata. J Reprod Med 31(9):804,1986.
   
6. A Patient Guide: HPV in Perspective. American Social Health Association, 1995.

1. Osborne NG, Adelson MD. Herpes simplex and human papillomavirus genital infections: controversy over obstetric management. Clin Obstet Gynecol 33(4):801,1990.
   
2. Sexually Transmitted Diseases Treatment Guidelines. MMWR 42(RR-14):83,1993.
   
3. Cripe TP. Human papilloma viruses: pediatric perspectives on a family of multifaceted tumorigenic pathogens. Pediatr Infect Dis J 9(11):836,1990.
   
4. Shah K, Kashima H, Polk BF, et al. Rarity of cesarean delivery in cases of juvenile-onset respiratory papillomatosis. Obstet Gynecol 68(6):795,1986.
   
5. Hallden C, Majmudar B. The relationship between juvenile laryngeal papillomatosis and maternal condylomata acuminata. J Reprod Med 31(9):804,1986.
   
6. A Patient Guide: HPV in Perspective. American Social Health Association, 1995.