HPV infection is considered a sexually transmitted disease common in sexually active young women, with an estimated prevalence between 20% and 46%[4
]. In pregnant women the prevalence of HPV infection fluctuates around 25%[24
]. Prior studies suggested that the HPV infection could be transmitted during the perinatal period [26
]. This is a study between mother and newborn, whose type specific HPV agreement between the pair characterized the vertical transmission of the virus.
The presence of HPV-DNA in the maternal genital area may be considered a risk factor for fetal exposure to the virus. In this study, among the types of HPV identified in the maternal genital samples, 54.9% were considered a high carcinogenic risk. HPV infection has been identified in 1% to 20%[27
] of babies newly born to pregnant women who do not show any evidence of cervical HPV infection, and in 5% to 72%[30
] in newborns of women with a diagnosis of the viral infection during pregnancy. Gajewska et al. (2006)[25
], detected HPV genital (prevalence of HPV types 6/11 – 18%; HPV type 16 – 13%) in 26% (n = 10/39) of the pregnant women and observed a high percentage (70%) of HPV transmission from mother to neonate. Rice et al. (2000)[32
] identified HPV-DNA type 16 in samples of the oral cavity of children aged 3 to 11 years, and related the results to possible perinatal and interfamilial transmission. On concluding, these authors suggested that in future vaccination programs and studies of the different transmission routes of HPV should be introduced.
Sedlacek et al. (1989)[33
] showed the presence of HPV-DNA in nasopharyngeal aspirates of newborns delivered by vaginal route to mothers with HPV-DNA in uterine cervix cells. Authors have described the presence of HPV-DNA in amniotic liquid[13
], in cord blood[14
], in fetuses with malformations[7
] and in specimens from first trimester spontaneous abortions[34
]. The presence of HPV-DNA in newborns no implies the presence of viral infections but may demonstrate the mechanism by which the virus can be transmitted during the perinatal period.
In the study discussed here, on analyzing the samples of buccal and body scrapings, nasopharyngeal aspirate and arterial cord blood obtained in the first minutes of life, it was observed that 11 NB (22.4%, n = 11/49) were positive for HPV-DNA research, 54.9% of which were considered of high carcinogenic risk. Concordance of the type specific HPV was also observed between mother/NB in 16.3% (n = 8/49) of the pairs, characterizing the possibility of transmission of HPV-DNA intrauterine or during the delivery. The different types of HPV identified among the mother/newborn pairs (6.1%, n = 3/49) can be explained by contamination of the sample or of the PCR technique (unlikely, due to the methodologies used to prevent contamination of the PCR methods), or by infection from multiple types of HPV, or by viral subtypes and/or variants.
This study also showed the efficacy of the multiple sample methodology in the newborn, eliminating false negative results for HPV-DNA research. The results obtained corroborate Mazzatenta et al. (1996)[35
] who in their study concluded that a simple sample can have a satisfactory result in clinical screening, even if it is not a reliable method to evaluate the risk of vertical transmission of HPV.
The behavior of the presence of HPV-DNA in newborns can be understood by prospective follow up studies and obtaining repeated samples. The present study suggests that the presence of the HPV-DNA in children of mothers HPV-DNA+ in genital sample fluctuates during the first six months of life. Out of the 11 NB who presented HPV-DNA+, only two children continued HPV-DNA+ in samples obtained from the buccal after the first month of life. Three children (6.1%, n = 3/49) became HPV-DNA+ during the first month of life. When children were evaluated in the 6th
month of life, all of them became HPV-DNA negative, even if a new case of a HPV-DNA+ appeared for buccal samples. This "regression" of the presence of HPV-DNA in buccal could be explained by the silent neutralization of antibodies that have migrated transplacentally, from the mother to the fetus, and that are functionally active in neonatal circulation, or contamination by maternal infected cells in NB delivered vaginally and that tend to disappear during the first months of life. This diminished number of HPV-DNA+ children could be explained by the results shown by Kawana et al. (2003)[36
]. These authors found type 6 anti-HPV antibodies in the maternal blood and in the blood of newborns of infected mothers. The authors suggested that their finding should be better defined and that their study could be considered an important step to understand the prevention of vertical transmission of HPV. Kaye et al. (1996)[37
], Cason et al. (1995)[6
], Pakarian et al. (1994)[29
] Tenti et al. (1999)[38
] demonstrated that the HPV-DNA in children examined at three different moments, tends to become negative between birth and the 6th month of life. Puranen et al. (1997)[9
] reported the persistence of HPV throughout the first 3 years of life, although the persistence of oral HPV-DNA was not detected in other follow up studies[27
The new cases of children who were HPV-DNA+ in the buccal at the end of the first (n = 3) and sixth (n = 1) month of life, could be explained by the agreement (100%) of the type specific HPV between mother/NB. This agreement of HPV-DNA suggests that these children may have been exposed to HPV-DNA: during the intrauterine period or during the delivery and that the HPV-DNA was only identified after birth[39
]; or during the post-birth period, when caring for the child (interfamilial transmission – mother/child)[40
One (n = 1/63, 1.6%) child had anogenital warts (HPV-DNA type 6/11) in the 12th
month of life. The incidence of anogenital warts in children has increased dramatically since 1990 [41
]. Before 1990, only 136 cases of anogenital warts had been reported in children, yet between 1990 and 1994, at least 326 additional cases were described [42
]. The increase in incidence of anogenital warts in children is thought to parallel the increase in incidence of anogenital warts in the adult population[43
]. Adams (2001)[44
] classification scale for evaluation medical findings of suspected sexual abuse lists anogenital warts/condyloma in a child younger than 2 years of age as a nonspecific finding for sexual abuse-perinatal transmission must be considered. Vertical transmission can occur through the bloodstream prior to birth, or at the time of birth, as the infant passes through the infected birth canal. Delivery via cesarean section does not eliminate the possibility of vertical transmission of HPV; there are reports of congenital condyloma after cesarean section without premature rupture of membranes[43
]. HPV can be transmitted no sexually from direct contact with caretaker contaminate with genital HPV or common warts [41
]. For example, caretakers with genital warts who touch or scratch their genitals and then without washing their hands change a baby's diaper or assist a child with toileting/bathing may transmit the virus to the child's genitals. A caretaker with common warts of the hands could transmit HPV in the same manner. HPV transmission via contact with contaminated objects or surfaces is possible [43
]. Sexual abuse must never be eliminated when considering possible modes of transmission for anogenital HPV in younger children[42
In three cases no concordance of the type specific HPV between mother/NB were observed. The different types of HPV-DNA identified among the mother/NB pairs can be explained by infection from multiple types of HPV, or by viral subtypes and/or variants.
The positive and significant correlation between presence HPV-DNA+ in the newborn or child and the maternal variables "history of immunodepression" (HIV, p = 0.007) may be related to the special characteristics of the pregnancy, especially to the changes in the hormonal and immunological balance prevailing during this period, which could favor vertical transmission of the virus. In adults, the risk factors for HPV-DNA transmission have been well established. The chances of perinatal transmission and the differences in the known rates of HPV-DNA transmission, are probably more closely related to the viral load of the infected cells than to the risk factors established for HPV infection[38
Although the nested multiplex PCR methodology is used to identify only 9 types of HPV represented as the most prevalent in the city of Caxias do Sul, it had an excellent performance to identify maternal HPV-DNA, and also considerably increased the total number of pregnant women with infections caused by multiple viruses. In the samples of newborns, the nested multiplex PCR showed its great sensitivity and specificity to identify HPV. The use of that method was also essential to evaluate the agreement of type specific HPV-DNA between the maternal/newborn samples, thus defining the perinatal transmission rates.
The perinatal transmission of HPV-DNA was suggested when concordance of the type specific HPV was observed between mother/NB and mother/child: eight newborns, three children at the end first month of life and a child in the 6th month of life. In conclusion, perinatal transmission of HPV-DNA was suggested in 24.5% (n = 12/49) of the newborns of mothers with genital warts or intraepithelial lesions of the uterine cervix. Thus, a different management can be adopted for each of the different stages (pre-gestational, gestation, delivery, and the first months post partum), both from the diagnostic and therapeutic perspective. Clinical observation of the mother and the newborn must be maintained, and preventive educational measures established for forms of HPV-DNA transmission, besides effective strategies for specific immunization.