Questions Surround Transmission Route of Human Papillomavirus

By Sharon Myoji Schnare, RN, FNP, CNM, MSN

Summary—Estimates indicate 6-60% of women are infected with human papillomavirus (HPV), which is implicated in causing cervical cancer and intraepithelial neoplasia (CIN) in women as well as laryngeal papillomytosis in infants and children.1 A study of 55 women was conducted to determine the incidence of HPV in amniotic fluid in a general population of pregnant patients. Polymerase chain reaction (PCR) analyses of cervical-vaginal mucus from 42 of the women found 10 subjects were positive for HPV, although all amniotic fluid samples were HPV-negative. Researchers concluded the study did not support prenatal transmission of HPV via amniotic fluid.2 Other studies report opposing results. Considerable research is needed before definitive answers are available for patients and clinicians. Pregnant patients with HPV should be informed of the diagnosis and counseled about its risks. They do not require special treatment unless condylomatous lesions create a hazard to normal delivery. Cesareans are not recommended.

Human papillomavirus (HPV) is one of the most common sexually transmitted diseases (STDs), and it has been estimated that 6-60% of women are infected.1 Up to 90% of women with cervical intraepithelial neoplasia (CIN) have concomitant HPV infection. The incidence of HPV infection in the cervix and vagina of pregnant women ranges from 13-35%.3,4 Laryngeal papillomas are known to occur in infants whose mothers have genital warts (one form of HPV) at the time of delivery.5 Finding laryngeal papillomatosis in neonates raises the question of possible transmission of HPV from mother to fetus via placenta or amniotic fluid.

Fifty-five pregnant women enrolled in a multicenter study at William Beaumont Army Medical Hospital and Texas Tech Health Sciences Center, both in El Paso, which proposed to determine the incidence of HPV in amniotic fluid in a general population of pregnant patients.2 Forty-two women undergoing amniocentesis were evaluated for evidence of HPV using polymerase chain reaction (PCR) to amplify the amniotic and cervicalvaginal fluid DNA. Indications for amniocentesis were:

• genetic counseling, 72%;

• determination of fetal lung maturity, 24%;

• and rule-out chorioamnionitis, 4%.

Investigators obtained and analyzed cervical-vaginal mucus from 42 of the 55 subjects. Results showed:

• 10 (23.8%) of the subjects were positive for HPV on PCR analysis.

• One (2.4%) of two subjects with prenatal Pap smears suggesting HPV was negative for HPV.

• Two (4.1%) of the 49 patients with prenatal Pap smears evidenced dysplasia.

• Four (8.2%) reported a lifetime history of dysplasia.

PCR analysis of amniotic fluid revealed the absence of HPV in all the patients. The two women with documented cervical intraepithelial neoplasia (CIN I and II), also demonstrated negative findings for HPV in their amniotic fluid. Researchers concluded the absence of HPV in the amniotic fluid of women with confirmed cervical HPV does not support of vertical prenatal transmission of HPV.2

In general, colleagues support the investigators' conclusions. In one study, the infants of 112 women with historic, clinical, or DNA evidence of genital HPV during pregnancy were evaluated periodically for 36 months.6 During 479 infant visits, HPV DNA was detected in only:

• five (1.5%) of 335 genital samples;

• four (1.2%) of 324 anal samples;

• none (0%) of 372 oral or nasopharyngeal samples.

In comparison, the same study found only three (4%) positive-reacting specimens from 80 infants born to women testing positive for HPV at 34 weeks gestation. They also found positive-reacting specimens from five (8%) of 63 infants born to women testing negative for HPV at 34 weeks gestation. Researchers pointed out that study results do not rule out perinatal transmission of HPV, but it does suggest the risk of perinatal transmission of genital HPV from infected mothers is only 2.8% (confidence interval 95%).6

One author wrote that the risk of intrapartum transmission is extremely low, cesarean delivery for the prevention of HPV transmission is not indicated, and that "Recent work has demonstrated that HPV DNA can be transmitted transplacentally."7

The risk of viral transmission to the neonate has been estimated as less than one in 10,000, and cesarean is only recommended for patients with large condylomata that may be obstructive during delivery.1

The Other Side of the Coin

Rarely do scientists find overwhelming evidence for only one possible conclusion in scientific inquiry. The question of perinatal transmission of maternal HPV is no exception. A study reported in February 1998 found HPV infection three times as prevalent in specimens from spontaneous abortion than in specimens from elective abortion.8 Syncytiotrophoblasts were identified as the cellular target of HPV. Trophoblast cells maintain contact between placenta and maternal tissue to facilitate nutrient exchange. Authors propose the hypothesis that HPV infection may have altered characteristics of the trophoblasts leading to compromised gestation.

An earlier study (May 1996) reported HPV might be transmitted to the fetus during gestation or delivery.9 This study stated that the possibility of HPV-DNA transmission from mother to fetus was high when maternal PCR is positive at delivery or in the event of a high viral load. The author points out the risk of laryngeal papillomatosis in the first five years of life may spread to the point of causing severe respiratory obstruction or aphonia. The author recommends checking all HPV-DNA positive neonates one year post-delivery.

Studies published in 1994 and 199310,11 found HPV in the amniotic fluid of women with a history of cervical HPV. In one study, the rate was as high as 50%, and in women with CIN, the rate was 100%.11

In August, a French scientist reported a virologic study of amniotic fluid and placenta from a patient diagnosed with epidermodysplasia verruciformis (EV) (a form of warty lesion caused by HPV).12 Analyses found variants of EV HPV5, HPV8, HPV24, and HPV36 and of HPV3 in skin lesions. Interestingly, HPV5, HPV8, HPV25\4, and HPV3 were detected in the patient's placenta but had not been found in peripheral blood mononuclear cells collected two years and six months before cesarean. The author commented that this makes bloodborne transmission unlikely. The same HPV variants were identified in the patient's cervical scrapes, which may indicate an ascending placental infection. In conclusion, the author reports that this first report of EV HPV in amniotic fluid, placenta, and cervical scrapes of an EV patient makes vertical transmission of EV HPV likely.13

Implications for Practice

The importance of HPV in women cannot be overlooked. (See patient education handout enclosed in this issue.) The possibility of perinatal transmission to fetus or neonate is sobering, as is the acknowledged risk for development of CIN or cervical cancer. While there is no doubt of the danger of HPV infection, more studies are needed to determine the extent of danger to a fetus or neonate and how such transmission occurs, if it does. The implications for practice however, are quite clear.

Pregnant patients with evidence of HPV on PAP smears or with condyloma acuminata lesions should be told they have HPV and counseled about its association with cervical cancer. Pregnant women with evidence of HPV do not need special treatment in pregnancy unless condylomatous lesions are large enough to obstruct the birth canal, or if lesions present a potential bleeding problem at delivery. Cesarean delivery currently is not recommended as a preventive measure to reduce HPV transmission to infants because little evidence supports its use. Newborns who later develop hoarseness should be evaluated for laryngeal papillomatosis. Women with HPV should be encouraged, as all women should, to have annual PAP smears, avoid cigarette smoking, and use condoms, unless they are in monogamous relationships.

References

1. Jackson SL, Soper DE. Prescribing in pregnancy: sexually transmitted diseases in pregnancy. Obstet Gynecol Clinics 1997;24;641-642.

2. Maxwell LG, Carlson J, Zakarean M, et al. The absence of human papillomavirus in amniotic fluid. J Lower Genital Tract Disease 1998;2:151-154.

3. Schneider A, Holtz M, Gissmann L. Increased prevalence of human papillomavirus in the lower genital tract of pregnant women. Int J Cancer 1997;48:198-201.

4. Peng, TC, Searle CP, Shah KV, et al. Prevalence of human papillomavirus infections in term pregnancy. Am J Perinatol 1990;7;89-192.

5. Robinson KM. Sexually transmitted infections. In McCance K, Huether S. Pathophysiology: The Biologic Basis for Disease in Adults and Children. St. Louis: Mosby; 1998:834.

6. Watts DH. Low risk of perinatal transmission of human papillomavirus: results from a prospective cohort study. Am J Obstet Gynecol 1998;178:365-73.

7. Scott JR, Disaia PH, Hammond CB, et al (eds). Viral infections. In Scott: Danforth's Obstetrics and Gynecology. 7th ed. Philadelphia: Lippincott-Raven Publishers; 1994.

8. Hermonat PL. Trophoblasts are the preferential target for human papillomavirus infection in spontaneously aborted products of conception. Hum Path 1998;29: 170-174.

9. Alberico S. Maternal-fetal transmission of human papillomavirus. Minerva Ginecol 1996;48:199-204.

10. Armbruster-Morales E, Ioshimoto LM, Leao E, et al. Detection of human papillomavirus deoxyribonucleic acid sequences in amniotic fluid during different periods of pregnancy. Am J Obstet Gynecol 1993;169: 1074-1075.

11. Armbruster-Morales E, Ioshimoto LM, Leao E, Zugaib M. Presence of human papillomavirus DNA in amniotic fluids of pregnant women with cervical lesions. Gynecol Onc 1994;54:152-158.

12. Huether SE. Structure, function, and disorders of the integument. In McCance KL, Huether SE. Pathophysiology: The Biologic Basis for Disease in Adults and Children. St. Louis: Mosby; 1998:1539.

13. Favre M. A possible vertical transmission of human papillomavirus genotypes associated with epidermodysplasia verruciformis. J Invest Derm 1998:111: 333-336.

For More Information

• To obtain a copy of 1998 Guidelines for Treatment of Sexually Transmitted Disease, published in the Morbidity and Mortality Weekly Report 1998;47(No. RR-1);1-118, contact:

Office of Communication, NCHSTP, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop E-06, Atlanta, GA 30333. Tele phone: (888) 232-3228. Press 2,5,1,1, to go straight to STD info that you can order by voice mail. No charge for single copy. Fax: (404) 639-8628.

The guidelines also are available on the World Wide Web: http://www.cdc.gov. This report and many others are available via the Wonder Web site, http://wonder.cdc.gov/. You will be asked to register (free) and to logon with each use.