C

o
p
i
a

a
u
t
o
r
i
z
a
d
a

p
o
r

C
D
R
Distribution of maternal and infant human papillomavirus: risk factors
associated with vertical transmission
H.S. Hahn
a
, M.K. Kee
b
, H.J. Kim
c
, M.Y. Kim
a
, Y.S. Kang
d
, J.S. Park
e,
**, T.J. Kim
a,
*
a
Department of Obstetrics and Gynaecology, Cheil General Hospital and Womens Healthcare Centre, Kwandong University, College of Medicine, Seoul,
Republic of Korea
b
Division of AIDS, Korea Centres for Disease Control and Prevention, Korea National Institute of Health, Republic of Korea
c
Department of Preventive Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea
d
Laboratory of Research and Development for Genomics, Cheil General Hospital and Womens Healthcare Centre, Kwandong University, College of Medicine,
Seoul, Republic of Korea
e
Department of Obstetrics and Gynaecology, College of Medicine, The Catholic University of Korea, Seoul St. Marys Hospital, Seoul, Republic of Korea
1. Introduction
Human papillomavirus (HPV) is a sexually transmitted virus
that gives rise to anogenital warts and cervical cancer in adults [1],
and laryngeal papilloma, conjunctival papilloma and recurrent
respiratory papillomatosis in children [26]. Recurrent respiratory
papillomatosis is transformed into malignant laryngeal carcinoma
in 35% of cases [6]. HPV infection is usually caused by sexual
intercourse, but non-sexual transmission has also been reported,
including vertical transmission from mother to neonate, horizontal
transmission from those in close contact with the neonate
including other family members, auto-inoculation from one
infection site to another, and indirect transmission through
contaminated objects [7].
The rate of HPV infection in pregnant women ranges widely
from6% to 65%, with an average of approximately 24%. The rate of
vertical transmission of HPV from mother to neonate also ranges
widely from 4% to 72% depending on regional and study population
differences [8,9].
This prospective study reports the rate of vertical transmission
of HPV infection in pregnant women in Korea. The study aimed to
evaluate the rate of HPV infection in pregnant women, and identify
the risk factors associated with vertical transmission. In addition,
the study evaluated whether neonatal HPV infection is acquired
through transplacental transmission during pregnancy.
European Journal of Obstetrics & Gynecology and Reproductive Biology 169 (2013) 202206
A R T I C L E I N F O
Article history:
Received 9 September 2012
Received in revised form 5 December 2012
Accepted 28 February 2013
Keywords:
Vertical transmission
Mode of delivery
HPV type
HPV load
A B S T R A C T
Objective: To evaluate the rate of human papillomavirus (HPV) infection in pregnant women and their
neonates, and the risk factors associated with vertical transmission of HPV infection from mothers to
neonates.
Study design: Cervical HPV testing was undertaken in pregnant women over 36 weeks of gestation, and
mouth secretions and oral mucosa of neonates were tested for HPV immediately after delivery. HPV-
positive neonates were rechecked 2 months postpartum to identify the persistence of HPV infection. In
HPV-positive mothers, the placenta, cord blood and maternal peripheral blood were also analysed for
HPV to conrm whether transplacental HPV infection occurred.
Results: HPV was detected in 72 of 469 pregnant women (15.4%) and in 15 neonates (3.2%). Maternal
HPV positivity was associated with primiparity and abnormal cervical cytology. The rate of vertical
transmission was 20.8%, and all HPV-positive neonates were born from HPV-positive mothers. Vertical
transmission was associated with vaginal delivery and multiple HPV types in the mother. Neonates with
HPV showed a tendency for higher maternal total HPV copy number than neonates without HPV, but this
difference was not signicant (p = 0.081). No cases of HPVinfection were found in the infants at 2 months
postpartum, and no HPV was detected in placenta, cord blood or maternal blood.
Conclusions: Vertical transmission of HPV is associated with vaginal delivery and multiple HPV types in
the mother; however, neonatal HPV infection through vertical transmission is thought to be a transient.
2013 Elsevier Ireland Ltd. All rights reserved.
* Corresponding author at: 1-19 Mukjeong-dong, Jung-gu, Cheil General Hospital
and Womens Healthcare Centre, Kwandong University College of Medicine, Seoul
100-380, Republic of Korea. Tel.: +82 2 2000 7577; fax: +82 2 2000 7183.
** Corresponding author at: 505, Banpo-dong, Seocho-gu, Seoul St. Marys
Hospital, The Catholic University of Korea, Seoul, 137-701, Republic of Korea.
Tel.: +82 2 2258 2810; fax: +82 2 2258 2724.
E-mail addresses: jspark@catholic.ac.kr (J.S. Park), kimonc@hotmail.com
(T.J. Kim).
Contents lists available at SciVerse ScienceDirect
European Journal of Obstetrics & Gynecology and
Reproductive Biology
j ou r nal h o mepag e: w ww. el sevi er . co m / l oc at e/ ej og r b
0301-2115/$ see front matter 2013 Elsevier Ireland Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.ejogrb.2013.02.024
15/04/2014
C
o
p
i
a

a
u
t
o
r
i
z
a
d
a

p
o
r

C
D
R
2. Materials and methods
2.1. Study population
Pregnant women over 36 weeks of gestation who planned to
give birth at the Cheil General Hospital and Womens Healthcare
Centre were recruited between March 2010 and April 2011. The
institutions ethical committee approved this research, and all the
participants gave informed consent to participate. Women with
severe intrauterine growth restriction, severe oligohydramnios,
preterm premature rupture of membranes, severe hypertension
during pregnancy, a history of malignancy within the last 5 years,
liver cirrhosis, renal failure, chronic disease affecting maternofetal
immunity, a history of psychological disease and alcoholism were
excluded. The rate of vertical transmission, and demographic and
reproductive characteristics associated with vertical transmission
were analysed, and the HPV viral loads of HPV-positive mothers
were measured to investigate the relationship between vertical
transmission and viral load.
2.2. Samples
Cervical HPV testing was undertaken in the pregnant women,
and mouth secretions and oral mucosa of the neonates collected
immediately after delivery were tested for HPV. HPV-positive
neonates were rechecked at 2 months postpartum to verify
persistence of the HPV infection. In HPV-positive mothers, the
placenta, cord blood and maternal peripheral blood were also
analysed for HPV to conrm whether transplacental HPV infection
occurred.
Maternal peripheral blood was taken before delivery, and
placenta and umbilical venous cord blood were obtained
immediately after delivery. A 2 2 cm sample of central placenta
including all tissue layers was taken, and the samples were xed in
neutral 10% formalin and processed in parafn blocks.
2.3. Isolation of DNA
DNA from exfoliated cervical cells, placenta and neonate oral
mucosa was isolated using a QIAGEN tissue genomic DNA Kit
(QIAGEN Inc., Valencia, CA, USA) according to the manufacturers
instructions. DNA from cord and maternal peripheral blood was
isolated using a QIAamp Blood Mini Kit (QIAGEN) according to the
manufacturers instructions.
2.4. SYBR green I real-time polymerase chain reaction (PCR)
SYBR Green I real-time PCR reactions were performed with
4 pmol GPM7 forward primers (F1, F2), 8 pmol Cy5-labelled reverse
primer (R) and 2 ml DNA sample, containing 10 ml of 2X SYBRGreen I
Master Mix (Roche Diagnostics GmbH, Mannheim, Germany) and
0.5 units uracil DNA glycosylase in a 20 ml reaction. The nucleotide
sequences (5
0
3
0
) of GPM7 F1 and F2 are AGTGGT CATCCWTTWTT-
WAATAAATTKGATGA and AGTGGCCATCCWTTDTWKAA TAG-
GYWKGATGA, respectively. The nucleotide sequence of GPM R
(5
0
3
0
) is Cy5-CCAWAGCCWGTATCWACCATRTCACCATC. SYBR
Green I real-time PCR conditions for human beta globin were the
same except for the primer condition, which was conducted with
5 pmol GPM F1, F2 and Cy5-labelled GPM R.
2.5. Cheil HPV DNA chip assay
Each product (5 ml) from the SYBR Green I real-time PCR of HPV
and human beta globin was denatured in a single tube at 95 8C for
10 min, and transferred immediately to ice. The mixture contain-
ing real-time PCR products and hybridization buffer (5X SSC, 0.2%
SDS) was injected slowly into the hole of cover slips on the
prepared slides. Hybridization was performed at 60 8C for 30 min
under high humidity. After hybridization, the slides were washed
three times with washing solution (1X SSC, 0.1% SDS) and rinsed
three times with 1 SSC. After drying the slides, HPV types were
identied using a chip scanner (NimbleGen MS 200, Roche
NimbleGen, Switzerland) and analysed with GenePix Pro Version
6.0 (Axon Instruments, Inc., Union City, CA, USA). The Cheil HPV
DNA chip can detect the presence of HPV 16, 18, 31, 33, 35, 39, 45,
51, 52, 53, 56, 58, 59, 66, 67, 68, 68a and 82 (high-risk types) and
HPV 6, 11, 30, 32, 40, 42, 43, 44, 54, 55, 62, 69, 70, 72, 81, 84, 90 and
91 (low-risk types).
2.6. In situ hybridization (ISH)
To conrm the absence of placental HPV by PCR, HPV DNA in
situ hybridization (ISH) was conducted on the placentas of eight
HPV-positive women whose HPV was detectable using Ventana
INFORM HPV probes (Ventana Medical Systems Inc., Tucson, AZ,
USA). For ISH, 6 mm-thick sections were cut from formalin-xed
and parafn-embedded placental samples. The sections were
hybridized with HPV DNA probe cocktails after proteolytic
treatment. The Family 6 probe cocktail has an afnity for HPV
genotypes 6 and 11, and the Family 16 probe cocktail has an
afnity for HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58,
and 66. Placental cells harbouring HPV DNA were identied by
haematoxylin-eosin staining, using the HPV genome in SiHa cells
as the positive control.
2.7. Statistical analysis
To identify the factors associated with HPV infection in
pregnant women and neonates, participants were assigned into
one of two groups according to the presence or absence of HPV.
Continuous and discrete variables were compared using Students
t-test and Chi-squared test, respectively. A p-value <0.05 was
considered statistically signicant with the use of a two-sided
test.
Fig. 1. In situ hybridization of human papillomavirus (HPV) DNA in placental sections. (A) Chorionic plate, (B) Chorionic villi and (C) SiHa cells, as a positive control. The
positive control was hybridized with HPV DNA probes, and blue colour indicates the presence of HPV DNA. Panels A and B show an absence of HPV DNA. H&E stain X200.
H.S. Hahn et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 169 (2013) 202206 203
15/04/2014
C
o
p
i
a

a
u
t
o
r
i
z
a
d
a

p
o
r

C
D
R
3. Results
In total, 500 pregnant women were enrolled during the study
period, and 469 patients with cognate neonate samples available
for analysis were included in this study. Three hundred of these
women (64.0%) had a vaginal delivery and 169 women (36.0%) had
a caesarean section. The rate of maternal HPV infection was 15.4%
(72/469), and there were no signicant differences in age,
gravidity, number of abortions, bacterial genital infection and
gestational diabetes mellitus between the HPV-positive and HPV-
negative groups (Table 1). Maternal HPV positivity was associated
with abnormal cervical cytology (p = 0.001) and primiparity
(p = 0.015). The rate of neonatal HPV detection was 3.2% (15/
469), and all of these neonates had HPV transmitted from their
mothers: therefore, the rate of vertical transmission was 20.8% (15/
72). No babies with HPV-negative mothers showed HPV positivity.
The vertically transmitted HPV genotypes were considered to be
concordant if the HPV genotypes detected in the baby corre-
sponded with those in the mother. All motherneonate pairs in this
study showed concordant HPV genotypes (Table 2). These results
suggest that all HPV-positive neonates are infected through
vertical transmission from their mothers. Of the neonatal HPV
genotypes, HPV 53 and 16 were detected most frequently (three
cases and two cases, respectively). Other HPV-type infections were
also detected. To check persistent neonatal HPV infection, HPV
DNA tests were repeated at 2 months postpartum for all 15 HPV-
positive neonates, and all showed negative ndings.
HPV 16 was the most common genotype found in the maternal
cervix (n = 9, 12.5%), followed by HPV 53 (n = 7, 9.7%), and HPV 56
and 70 (n = 6, 8.3%). Multiple HPV types were noted in 10 cases
(13.9%). Thirty-nine of 72 HPV-infected women (54.2%) were
infected with at least one high-risk type of HPV.
Gestational age, birth weight, bacterial genital infection, length
of labour, premature rupture of the amniotic membrane and risk of
HPV type were not signicantly different when comparing HPV-
positive women by neonatal HPV status (Table 3). The risk of
vertical transmission of HPV from the mother to the neonate was
higher in women who had a vaginal delivery and women with
multiple HPV types (p = 0.031 and p = 0.001, respectively).
In the data on HPV load (Table 4), neonates with HPV infection
had a tendency to be associated with a higher maternal total HPV
copy number than neonates without HPV infection, but this
difference was not signicant (p = 0.081). There were no differ-
ences in maternal HPV copy number infected per cervical cell
between HPV-positive and HPV-negative neonates (p = 0.880).
To conrm whether neonatal HPV infection occurred through
the placenta during pregnancy, placenta, cord blood and maternal
peripheral blood were tested by PCR. No HPV was detected in the
placenta, cord blood or maternal peripheral blood. ISH using HPV
DNA probes showed no HPV DNA in the placenta. These results
suggest that all cases of vertical transmission of HPV in this study
occurred through an infected birth canal and not through a
transplacental pathway (Fig. 1).
4. Comment
In this study, primiparity and abnormal cervical cytology were
associated with the prevalence of maternal HPV infection (Table 1).
Previous studies have reported that the prevalence of HPV
infection peaks in women aged <25 years, and then declines
and stabilizes at 45 years of age [10,11]. Age was not associated
with the prevalence of maternal HPV infection, but a signicant
association was found between parity and maternal HPV infection.
It is therefore likely that recent experience of sexual intercourse
inuenced the prevalence of HPV infection, because primiparous
women are more likely to have had sexual intercourse with other
sex partners more recently before marriage and pregnancy
compared with multiparous women. Typically, HPV infection is
transient and disappears within one year of initial exposure, but if
the HPV infection persists, it could develop into various HPV-
related diseases including cervical dysplasia and cancer [12].
Table 1
Demographic characteristics according to maternal human papillomavirus (HPV) status (n = 469).
Characteristics HPV (+) (n = 72) (%) HPV () (n= 397) (%) p-value
Age (years) 30 25 (19.2) 105 (80.8) 0.352
3135 30 (13.8) 188 (86.2)
36 17 (14.0) 104 (86.0)
Gravida 1 31 (15.3) 171 (84.7) 0.536
2 30 (17.1) 145 (82.9)
3 11 (12.0) 81 (88.0)
Para 0 54 (18.5) 238 (81.5) 0.015
1 18 (10.2) 159 (89.8)
Abortion 0 44 (13.7) 277 (86.3) 0.146
1 28 (18.9) 120 (81.1)
Bacterial genital infection () 71 (15.2) 395 (84.8) 0.386
(+) 1 (33.3) 2 (66.7)
GDM () 70 (15.6) 379 (84.4) 0.497
(+) 2 (10.0) 18 (90.0)
Abnormal cytology () 63 (14.0) 387 (86.0) 0.001
(+) 9 (47.4) 10 (52.6)
GDM, gestational diabetes mellitus.
Table 2
Concordance of human papillomavirus (HPV) genotypes in motherneonate pairs
(n= 15).
Participant no. Mother HPV Newborn HPV
Genital sampling Oral sampling
At delivery After 2 months
1 11, 56 11
2 40, 53 53
3 40, 44, 53 40, 44, 53
6 35 35
7 31, 58, 68 58
10 Other type Other type
28 16 16
29 16 16
34 6 6
197 45, 54 45, 54
204 90 90
207 81 81
213 56, 81 56
215 53 53
218 42, 90 42
H.S. Hahn et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 169 (2013) 202206 204
15/04/2014
C
o
p
i
a

a
u
t
o
r
i
z
a
d
a

p
o
r

C
D
R
Table 2 shows that all cases of vertical HPV infection were
temporary and persisted for less than 2 months. Cason et al.
reported that at 6 months postpartum, HPV 16 and HPV 18
infection persisted in 83% and 20% of infants infected with HPV at
birth, respectively, and suggested that long-term follow-up is
required for HPV-infected infants [13]. On the other hand,
Rombaldi et al. reported that all HPV DNA positive children at
birth were negative at 6 months postpartum [14]. The present
study is consistent with the work by Rombaldi et al., but discordant
with the study of Cason et al. This discordance could be due to
differences in study design, regional differences in the women
recruited, and differences in the method used to detect HPV. The
persistence of vertically transmitted HPV is a crucial issue for both
the mother and baby; therefore, a more thorough and planned
examination of pregnant women and HPV-infected neonates is
necessary if neonatal HPV persists and induces various HPV-
related diseases in infants.
Table 3 shows that multiple HPV types in pregnant women and
vaginal delivery were risk factors for vertical transmission. Only
one baby delivered by caesarean section was HPV positive, and
vaginal delivery had been attempted prior to surgery. As such, no
babies delivered by caesarean section, without at least an attempt
at vaginal delivery, were found to be HPV positive. Premature
rupture of membranes, long duration of labour, and infection with
a high-risk HPV type were not risk factors for vertical transmission
in this study. These results are not in accordance with some
previous studies. Tenti et al. reported that vertical transmission of
HPV is mainly caused by contamination during delivery, such as
premature rupture of membranes [15]. Bandyopadhyay et al.
analysed 135 pregnant women in India and reported that the
frequency of HPV transmission from infected mothers to their
infants was 18.42% (7/38), and the proportion of infants with HPV
infection delivered by caesarean section was 78.57% (11/14),
which was higher than the rate among infants delivered vaginally.
They suggested that caesarean section was not protective for
infants against perinatal HPV transmission [16]. However, Tseng
et al. [17] found that the risk of perinatal HPV transmission was
higher for vaginal deliveries. They analysed 301 pregnant women,
and found that 51.4% (18/35) of cases of vertical transmission of
HPV were delivered vaginally, whereas 27.3% (9/33) of cases were
delivered by caesarean section. Medeiros et al. [8] also observed a
higher risk of HPV infection following vaginal delivery compared
with caesarean section (relative risk 1.8).
Likewise, there are different ndings among studies regarding
the risk factors associated with vertical transmission of HPV and
the relationship between mode of delivery and HPV transmission.
These contradictory reports could be due to differences in HPV
detection methods, as well as different study populations with
various study designs. This study used the Cheil HPV DNA test to
detect HPV DNA, which is based on real-time PCR and micro-array
HPV genotyping. We were able to simultaneously identify the
genotype and quantify the viral load of HPV using the Cheil HPV
DNA chip. Conventional HPV DNA chips cannot quantify HPV load
as the PCR products do not reect the original template amount,
and the Hybrid Capture II system cannot detect HPV genotype as
the probes that cope with each HPV genotype are mixed [18]. We
tested novel primer sets (GPM7 F1, F2, R) that target the conserved
L1 region of the HPV genome to detect the 36 different HPV types
and to evaluate viral load infected per cervical cell. The generated
Cy5-labelled RT-PCR products are used directly to screen genotype
on the micro-array. Although not signicant, neonates with HPV
infection had a tendency for higher maternal total HPV copy
number in this study compared with neonates without HPV
infection (p = 0.081, Table 4). As the total HPV viral load could show
differences due to variations in sampling procedures between
practitioners, different sample amounts and disparity between
study populations, we attempted to identify HPV copy number per
cervical cell and no signicant differences were found (p = 0.880).
Rombaldi et al. [19] reported transplacental HPV transmission
in 12.2% (6/49) of patients and placental infection in 24.5% (12/49)
of patients. They reported that transplacental HPV transmission
was responsible for 54.5% (6/11) of cases of vertical transmission.
Table 3
Reproductive characteristics associated with neonatal human papillomavirus (HPV) status in HPV-positive women (n = 72).
Characteristics HPV(+) (n = 15) (SD or %) HPV() (n = 57) (SD or %) p-value
Gestational week 39.5 (0.8) 39.4 (1.0) 0.682
Birth weight (g) 3262 (303) 3298 (334) 0.696
Genital infection () 15 (21.1) 56 (78.9) 0.605
(+) 0 (0) 1 (100)
Length of labour (min) (n = 61) 965 (715) 965 (723) 0.999
PROM () 7 (17.5) 33 (82.5) 0.436
(+) 8 (25.0) 24 (75.0)
Mode of delivery CS 1 (4.8) 20 (95.2) 0.031
VD 14 (27.5) 37 (72.5)
Risk of HPV type LR or other type 5 (15.2) 28 (84.8) 0.275
HR type 10 (25.6) 29 (74.4)
Number of HPV type Single 8 (12.9) 54 (87.1) 0.001
Multiple 7 (70.0) 3 (30.0)
SD: standard deviation; PROM: premature rupture of membranes; CS: caesarean section; VD: vaginal delivery; LR: low risk; HR: high risk.
Table 4
Human papillomavirus (HPV) load according to neonatal HPV status in HPV-positive women (n = 72).
Neonate HPV status HPV load in HPV-positive pregnant women
HPV copy no. HPV copy no./cell
Mean SD p-Value Mean SD p-Value
Negative (n= 57) 6.83 10
2
3.01 10
3
0.35 1.92
Positive (n = 15) 4.95 10
3
1.76 10
4
0.30 0.88
0.081 0.880
SD: standard deviation.
H.S. Hahn et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 169 (2013) 202206 205
15/04/2014
C
o
p
i
a

a
u
t
o
r
i
z
a
d
a

p
o
r

C
D
R
Tseng et al. [20] detected HPV DNA in cord blood samples, and
suggested that HPV DNA in cord blood is closely related to the
presence of HPV DNA in maternal peripheral blood mononuclear
cells and HPV infection through transplacental transmission. The
present ndings are contrary to these results, however, as no HPV
was detected in the placenta, cord blood or maternal peripheral
blood on PCR or ISH. These results suggest that vertical
transmission occurred through an infected vaginal canal and not
via a transplacental pathway. As Rombaldi et al. suggested, future
HPV DNA testing is necessary in the normal endometrium of
women in order to observe HPV intrauterine infection, and also to
identify the possibility of vertical transmission through a
transplacental pathway.
In summary, this study found that vertical transmission of HPV
is associated with vaginal delivery and multiple HPV types in the
mother, but it is a transient contamination. Therefore, there is no
need to be concerned about the HPV status of pregnant women, as
HPV transmission from mother to baby has no practical interest.
This study, however, had some limitations that may induce
potential bias and imprecision. The small number of HPV-positive
mothers and infants limited the power of the studys conclusions,
and other factors that are not accounted for may have affected
vertical transmission of HPV. Future studies with a larger number
of patients are required to resolve these limitations.
Funding
Grants from the Korea Center for Disease Control and
Prevention (No. 2010-E51007-00) and the Korean Healthcare
Technology R&D Project, Ministry of Health & Welfare, Republic of
Korea (A10206510111250100) supported this work.
References
[1] Sigurdsson K, Taddeo FJ, Benediktsdottir KR, et al. HPV genotypes in CIN 2-3
lesions and cervical cancer: a population-based study. International Journal of
Cancer 2007;121:26827.
[2] Montgomery SM, Ehlin AGC, Spare n P, Bjo rkste n B, Ekbom A. Childhood
indicators of susceptibility to subsequent cervical cancer. British Journal of
Cancer 2002;87:98993.
[3] Wiatrak BJ, Wiatrak DW, Broker T, Lewis L. Recurrent respiratory papillomas: a
longitudinal study comparing severity associated with human papilloma viral
types 6 and 11 and other risk factors in a large pediatric population. Laryngo-
scope 2004;114:123.
[4] Silverberg MJ, Thorsen P, Lindeberg H, Grant LA, Shah KV. Condyloma in
pregnancy is strongly predictive of juvenile-onset recurrent respiratory papil-
lomatosis. Obstetrics and Gynecology 2003;101:64552.
[5] Syrja nen K, Syrja nen S. Papillomavirus infections in human disease. New York:
J. Wiley & Sons; 2000. p. 1615.
[6] Syrja nen S. Current concepts on human papillomavirus infections in children.
APMIS 2010;118:494509.
[7] Syrja nen S, Puranen M. Human papillomavirus infections in children: the
potential role of maternal transmission. Critical Reviews in Oral Biology
and Medicine 2000;11:25974.
[8] Medeiros LR, Ethur AB, Hilgert JB, et al. Vertical transmission of the human
papillomavirus: a systematic quantitative review. Cadernos de Saude Publica
2005;21:100615.
[9] Smith EM, Ritchie JM, Yankowitz J, et al. Human papillomavirus prevalence
and types in newborns and parents: concordance and modes of transmission.
Sexually Transmitted Diseases 2004;31:5762.
[10] Herrero R, Hildesheim A, Bratti C, et al. Population-based study of human
papillomavirus infection and cervical neoplasia in rural Costa Rica. Journal of
the National Cancer Institute 2000;92:46474.
[11] Takakuwa K, Mitsui T, Iwashita M, et al. Studies on the prevalence of human
papillomavirus in pregnant women in Japan. Journal of Perinatal Medicine
2006;34:779.
[12] Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervi-
covaginal papillomavirus infection in young women. New England Journal of
Medicine 1998;338:4238.
[13] Cason J, Kaye JN, Jewers RJ, et al. Perinatal infection and persistence of human
papillomavirus types 16 and 18 in infants. Journal of Medical Virology
1995;47:20918.
[14] Rombaldi RL, Serani EP, Mandelli J, Zimmermann E, Losquiavo KP. Perinatal
transmission of human papilomavirus DNA. Virol J 2009;6:83.
[15] Tenti P, Zappatore R, Migliora P, Spinillo A, Belloni C, Carnevali L. Perinatal
transmission of human papillomavirus from gravidas with latent infections.
Obstetrics and Gynecology 1999;93:4759.
[16] Bandyopadhyay S, Sen S, Majumdar L, Chatterjee R. Human papillomavirus
infection among Indian mothers and their infants. Asian Pacic Journal of
Cancer Prevention 2003;4:17984.
[17] Tseng CJ, Liang CC, Soong YK, Pao CC. Perinatal transmission of human
papillomavirus in infants: relationship between infection rate and mode of
delivery. Obstetrics and Gynecology 1998;91:926.
[18] Min KJ, So KA, Lee J, et al. Comparison of the Seeplex HPV4A ACE and the
Cervista HPV assays for the detection of HPV in hybrid capture 2 positive
media. Journal of Gynecological Oncology 2012;23:510.
[19] Rombaldi RL, Serani EP, Mandelli J, Zimmermann E, Losquiavo KP. Transpla-
cental transmission of human papillomavirus. Virol J 2008;5:106.
[20] Tseng CJ, Lin CY, Wang RL, et al. Possible transplacental transmission of human
papillomaviruses. American Journal of Obstetrics and Gynecology 1992;166:
3540.
H.S. Hahn et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 169 (2013) 202206 206
15/04/2014