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doi:10.1111/jog.12155

J. Obstet. Gynaecol. Res. Vol. 40, No. 1: 200207, January 2014

Genotypic prevalence of human papillomavirus infection

during normal pregnancy: A cross-sectional study
Yun Hwan Kim1, Joong Shin Park2, Errol R. Norwitz8, Jeong Woo Park6, Sun Min Kim2,
Seung Mi Lee2,4, Chan-Wook Park2, Byoung Jae Kim2,4, Ja Nam Koo7, Ig Hwan Oh7 and
Yong Sang Song2,3,5
1

Department of Obstetrics and Gynecology, Ewha Womans University School of Medicine, 2Department of Obstetrics and
Gynecology and 3Cancer Research Institute, Seoul National University College of Medicine, 4Department of Obstetrics and
Gynecology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, 5Major in Biomodulation,
World Class University, Seoul National University, Seoul, 6Department of Obstetrics and Gynecology, Inje University College
of Medicine, Ilsan-Paik Hospital, Gyeonggi, 7Seoul Womens Hospital, Incheon, Korea; and 8Department of Obstetrics and
Gynecology, Tufts University School of Medicine, Boston, Massachusetts, USA

Abstract
Aim: Genital human papillomavirus (HPV) infection is a necessary factor in most cases of cervical cancer, but
malignant transformation requires the presence of additional cofactors such as pregnancy. Little is known
about the effect of pregnancy on genital HPV carriage. We therefore analyzed the prevalence and genotypic
patterns of genital HPV infections in normal pregnancies.
Methods: The prevalence of HPV infection was measured in 960 consecutive normal pregnant or post-partum
women by HPV-DNA chip analysis of cervical swabs. Data were analyzed by trimester and adjusted for
sociodemographic, reproductive and reported sexual history.
Results: The overall prevalence of HPV infection in the population was 24.3%. High-risk HPV genotypes were
detected in 68.2% of infected subjects, including HPV 16 (18.7%), 39 (16.4%), 53 (10.1%), and 56 (9.4%).
High-risk HPV genotypes were significantly more prevalent in the second trimester (23.8%) compared with the
other periods (first trimester, 13.2%; third trimester, 17.4%; post-partum, 15.1%; P = 0.010). However, the
high-risk HPV genotypes 16 or 18 were detected most frequently in the third trimester (7.2%) as compared to
the other periods (first trimester, 2.9%; second trimester, 5.2%; post-partum, 2.1%; P = 0.03). After adjusting for
confounding variables, overall HPV infection (odds ratio = 1.84, 95% confidence interval = 1.242.75) and
high-risk HPV genotypes (odds ratio = 1.94, 95% confidence interval = 1.233.05) were significantly more
common in the second trimester.
Conclusion: The second trimester may be the most vulnerable period in high-risk HPV infections, which
necessitates future investigations.
Key words: genotype, human papillomavirus, pregnancy, prevalence, risk factor.

Introduction
Genital human papillomavirus (HPV) infection is
regarded as a necessary factor in most cases of cervical
cancer,1 but is not sufficient to cause invasive disease.
Malignant transformation appears to require the pres-

ence of additional cofactors such as pregnancy,2,3

smoking and immunosuppression. Whether pregnancy
predisposes to HPV infection and/or malignant transformation is not known. A number of investigators
have proposed that the physiological and hormonal
changes in pregnancy may modulate immune function

Received: December 3 2012.

Accepted: April 16 2013.
Reprint request to: Professor Joong Shin Park and Professor Yong Sang Song, Department of Obstetrics and Gynecology, Seoul
National University College of Medicine, 28 Yeongeon-Dong, Jongno-Gu, Seoul 110-744, Korea. Email: jsparkmd@snu.ac.kr
Conflict of interest: The authors have no conflict of interest.

200

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Journal of Obstetrics and Gynaecology Research 2013 Japan Society of Obstetrics and Gynecology

HPV infection during normal pregnancy

leading to changes in the behavior of HPV infection.46

Some reports have suggested that susceptibility to, and
persistence of, HPV infection is increased during
pregnancy,4,7,8 whereas others found no differences in
HPV infections between pregnant and non-pregnant
women.9,10 However, most of these studies failed to
control for gestational age,11 and little is known about
the genotypic patterns of genital HPV infections in
normal pregnancies. Therefore, we designed a large
prospective cross-sectional study to determine the
HPV prevalence and genotypic pattern in relation to
gestational age in normal pregnancy.

Methods
We performed a prospective cross-sectional study of
healthy pregnant women presenting to a single obstetric clinic in Incheon, Korea. All women aged 18 years
or older with a sonographically confirmed intrauterine
pregnancy who visited the clinic for prenatal and/or
post-partum care between May 2009 and June 2010
were approached and offered inclusion in the study.
Subjects were excluded if they had evidence of immunosuppression (such as HIV infection, transplantation
or malignancy), a connective tissue disorder or were
receiving medications related to immune modulation
(such as corticosteroids). The study was approved by
the institutional review board (H-0901-030-268), and
written informed consent was obtained from all study
participants.
Each participant completed a comprehensive medical history questionnaire, which included questions
about sociodemographic characteristics, smoking,
drinking, Papanicolaou smear screening, reproductive
and sexual history, and use of contraception. Thereafter, all subjects underwent a routine gynecological
examination. Cervical swab samples were collected
using a liquid cytology device (SurePath Technology;
TriPath Imaging, Burlington, NC, USA). The 2001
Bethesda System terminology was used to report the
results of the cervical cytology.12 All women with
abnormal Papanicolaou test results were referred for
colposcopic examination and biopsy.
High- and low-risk HPV were classified according to
the consensus of the International Agency for Research
on Cancer (IARC).13 The presence of HPV-DNA in the
cervical swabs was detected using the GG HPV Genotyping Chip Kit (Goodgene, Seoul, Korea),14 which can
identify 40 HPV genotypes (6, 11, 16, 18, 26, 30, 3135,
39, 40, 4245, 5156, 58, 59, 61, 62, 6670, 72, 73, 8184,
90 and 91). The GG HPV Genotyping Chip Kit had a

sensitivity of 98100% and specificity of 98100% when

compared to the result of sequencing and another HPV
test kit, with minimum detection limit of 1 102 to
1 103 copies, according to the permission document
of the Korea Food and Drug Administration.
Sequences of the HPV L1 gene and human b-globin
gene were amplified and labeled by Cy5-dUTP (NEN
Life Science Products, Boston, MA, USA) to serve as
positive controls. A mixture of 10 mL of HPV amplified
product and 10 mL b-globin amplified product were
denatured by heating at 95C for 2 min, followed by
cooling for 3 min on ice. The samples were mixed with
50 mL of GG hybridization buffer (Goodgene) and
0.2% sodium dodecylsulfate, and then applied to a
HPV-DNA chip (Goodgene). The perfusion eight-well
chamber (Schleicher and Schuell BioScience, Dassel,
Germany) was then attached to the chip and used as a
hybridization reaction chamber. The hybridization was
performed at 40C for 30 min to 2 h, followed by
washing with 3 SSPE for 2 min, 1 Saline Sodium
Phosphate EDTA (SSPE) for 2 min, and air drying at
room temperature. The hybridization signal on the
HPV-DNA chip was visualized by using an Affymetrix
428 Array Scanner (Affymetrix, Santa Clara, CA, USA).
Each group was compared by anova for continuous
variables and by Pearson c2-test for categorical variables. Odds ratios (OR) for the detection of HPV-DNA
and corresponding 95% confidence intervals (CI) were
calculated by unconditional multiple logistic regression equations, and adjusted for maternal age (24,
2529, 3034 and 35 years). All variables that showed
statistically significant associations with HPV-DNA
in the age-adjusted analyses were then included in
the subsequent modeling. All statistical tests were
two-tailed, and statistical significance was defined as
P < 0.05. SPSS package ver. 17.0 (SPSS, Chicago, IL,
USA) was used for all analyses.

Results
One thousand consecutive women were approached for
inclusion in the study. Of these, 40 (4.0%) declined to
participate and 960 women were enrolled (first trimester, n = 380; second trimester, n = 193; third trimester,
n = 195; post-partum, n = 192), representing an acceptance rate of 96.0%. All subjects were Korean, and the
median age was 31 years (range, 1946). There were
significant differences in parity, level of education,
smoking, drinking, previous screening of cervical cytology, age of sexual debut and number of previous sexual
partners among the four groups (P < 0.05; Table 1).

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Journal of Obstetrics and Gynaecology Research 2013 Japan Society of Obstetrics and Gynecology

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Y. H. Kim et al.

Table 1 Demographic characteristics of participants at each trimester and post-partum

Age, years, mean SD

Age at menarche, years, mean SD
Age at first pregnancy, years, mean SD
Age at marriage, years, mean SD
No. of births, n (%)
0
1
2
Spontaneous abortion, n (%)
Ever
Induced abortion, n (%)
Ever
Years of education, n (%)
12
1316
17
Alcohol drinking, n (%)
Ever
Smoking, n (%)
Ever
Previous Papanicolaou smear, n (%)
Ever
20
Age at sexual debut, years, n (%)
2123
24
No. of previous sexual partners, n (%)
1
2
Husbands extramarital affair, n (%)
No
Uncertain
Possible
Contraception, n (%)
None
OCP
Condom
IUD

First
trimester
n = 380

Second
trimester
n = 193

Third
trimester
n = 195

Postpartum
n = 192

P-value*

31.1 4.0
14.2 1.4
28.5 4.0
28.6 3.5
182 (47.9)
156 (41.1)
42 (11.1)
70 (18.4)
88 (23.2)
120 (31.7)
233 (61.5)
26 (6.9)
65 (17.1)
87 (22.9)
276 (72.6)
55 (29.4)
66 (35.3)
66 (35.3)
94 (51.4)
89 (48.6)
160 (86.5)
24 (13.0)
1 (0.5)
80 (43.0)
15 (8.1)
86 (46.2)
5 (2.7)

31.4 4.1
14.3 1.3
28.6 4.1
28.6 3.0
132 (68.4)
41 (21.2)
20 (10.4)
24 (12.4)
45 (23.3)
75 (38.9)
101 (52.3)
17 (8.8)
4 (2.1)
32 (16.6)
113 (58.6)
33 (21.6)
42 (27.5)
78 (51.0)
84 (54.9)
69 (45.1)
122 (79.7)
29 (19.0)
2 (1.3)
56 (36.6)
23 (15.0)
71 (46.4)
3 (2.0)

30.9 3.6
14.3 1.3
28.9 3.7
28.5 2.7
146 (74.9)
42 (21.5)
7 (3.6)
28 (14.4)
35 (18.0)
76 (39.0)
109 (55.9)
10 (5.1)
11 (5.6)
23 (11.8)
131 (67.2)
26 (16.1)
55 (34.0)
81 (50.0)
106 (65.4)
56 (34.6)
139 (85.8)
20 (12.4)
3 (1.9)
53 (32.7)
14 (8.6)
94 (58.0)
1 (0.60)

31.5 3.9
14.4 1.3
28.8 3.7
28.9 2.9
0 (0.0)
141 (73.4)
51 (26.6)
28 (14.6)
38 (19.8)
57 (29.7)
121 (63.0)
14 (7.3)
18 (9.4)
53 (27.6)
133 (69.3)
38 (22.9)
60 (36.1)
68 (41.0)
58 (34.9)
108 (65.1)
142 (85.5)
23 (13.9)
1 (0.6)
59 (35.5)
20 (12.1)
81 (48.8)
6 (3.6)

0.41
0.42
0.70
0.70
<0.01*
0.25
0.43
0.17
<0.01*
<0.01*
0.01*
0.01*
<0.01*
0.50
0.12

anova for continuous variables and Pearson c2-test for categorical variables. *P < 0.05. IUD, intrauterine device; OCP, oral contraceptive pill;
SD, standard deviation.

Of the 960 study subjects, 940 (97.9%) had normal

Papanicolaou smear results, 12 (1.3%) had atypical
squamous cells of undetermined significance, five
(0.5%) had low-grade squamous intraepithelial lesions
and three (0.3%) had high-grade squamous intraepithelial lesions. All 20 women with abnormal cytological findings underwent colposcopic examinations and
biopsies. Of these, 11 had chronic cervicitis, six had
mild dysplasia (cervical intraepithelial neoplasia,
grade I [CIN I]) and three had severe dysplasia (CIN
III). None had invasive cervical cancer.
The prevalence of HPV-DNA among the 960 study subjects was analyzed by HPV genotype and cytological
findings. Overall, 233 (24.3%) were infected with HPV.
Of these, 159 (68.2%) were infected with high-risk HPV
genotypes. The most frequent high-risk HPV genotypes
were 16 (30/159; 18.7%), 39 (26/159; 16.4%), 53 (16/159;
10.1%) and 56 (15/159; 9.4%). Infection with multiple HPV
genotypes was seen in 18.5% (43/233) of study subjects.
The prevalence rate of HPV infection was significantly
different at different gestational ages: first trimester, 78

202

of 380 (20.5%); second trimester, 66 of 193 (34.2%); third

trimester (45 of 195 (23.1%); and post-partum period 44
of 192 (22.9%) (P = 0.004; Table 2 and Fig. 1). Moreover,
high-risk HPV genotypes were significantly more
prevalent during the second trimester (23.8%) as compared with other periods (first trimester, 13.2%; third
trimester, 17.4%; and post-partum, 15.1%; P = 0.01). On
the other hand, the high-risk HPV genotypes 16 or 18
were detected most frequently in the third trimester
(7.2%) as compared to the other periods (first trimester,
2.9%; second trimester, 5.2%; post-partum, 2.1%;
P = 0.03) (Table 2; Fig. 1).
Human papillomavirus DNA detection was
inversely related to maternal age. The risk of HPV
infection was significantly reduced in women aged
older than 30 years compared to those aged 24 years or
younger (age 3034 vs 24, OR = 0.46, 95% CI = 0.22
0.94; age 35 vs 24, OR = 0.34, 95% CI = 0.160.74)
(Appendix 1). The level of education was also inversely
associated with HPV infection. The risk of HPV infection was lower in women who had college education

2013 The Authors

Journal of Obstetrics and Gynaecology Research 2013 Japan Society of Obstetrics and Gynecology

HPV infection during normal pregnancy

Table 2 HPV infection at each trimester and post-partum

HPV infection
High-risk HPV genotype
Genotype 16 or 18
Low-risk HPV genotype
Multiple HPV infection

First
trimester
n = 380

Second
trimester
n = 193

Third
trimester
n = 195

Postpartum
n = 192

P-value*

78
50
11
37
14

66
46
10
26
12

45
34
14
17
11

44
29
4
20
6

<0.01*
0.01*
0.03*
0.44
0.39

(20.5)
(13.2)
(2.9)
(9.7)
(3.7)

(34.2)
(23.8)
(5.2)
(13.5)
(6.2)

(23.1)
(17.4)
(7.2)
(8.7)
(5.6)

(22.9)
(15.1)
(2.1)
(10.4)
(3.1)

All data are shown as n (%). Pearson c2-test. *P < 0.05. HPV, human papillomavirus.

Figure 1 Pattern of human papilloma virus (HPV) prevalence in relation to gestational age in normal pregnancy.
, HPV infection;
, high-risk HPV;
, genotype
16 or 18.

than those who had only attended high school

(OR = 0.66, 95% CI = 0.480.90) (Appendix 1).
The difference in HPV infection rates at different
periods of pregnancy persisted after adjustment for
maternal age. In this model, the second trimester was
associated with a significantly increased risk for HPV
infection (e.g. second vs first trimester, OR = 1.94, 95%
CI = 1.322.87) and for infection with a high-risk HPV
genotype (e.g. second vs first trimester, OR = 2.13, 95%
CI = 1.363.33) (Appendix 2). On the other hand, infection with high-risk HPV genotypes 16 or 18 was significantly higher in the third trimester of pregnancy
(e.g. third vs first trimester, OR = 2.67, 95% CI = 1.19
6.01) (Appendix 2). Among sexual indicators, the
number of previous sexual partners was significantly
associated with HPV type 16 or 18 infection (e.g. 2 vs
1, OR = 2.40, 95% CI = 1.065.42). However, no significant association was evident between HPV infection

and age of sexual debut, husbands extramarital affairs

and methods of contraception (Appendix 3).
Using multivariable logistic analysis to control for
other potential confounding variables, we confirmed
that the second trimester of pregnancy was associated
with a significantly increased risk for HPV infection
(e.g. second vs first trimester, OR = 1.84, 95% CI = 1.24
2.75) and for infection with high-risk HPV genotypes
(e.g. second vs first trimester, OR = 1.94, 95% CI = 1.23
3.05) (Table 3). Infection with the high-risk HPV genotypes 16 and 18 was significantly higher in the third
trimester of pregnancy (e.g. third vs first trimester,
OR = 4.51, 95% CI = 1.3515.04), and was related to the
number of previous sexual partners (e.g. 2 vs 1
partner, OR = 2.84, 95% CI = 1.246.54) (Table 3). The
risk for infection with multiple HPV genotypes was
decreased according to the level of education (e.g.
1316 vs 12 years, OR = 0.49, 95% CI = 0.270.90) and
parity (1 vs 0, OR = 0.12, 95% CI = 0.020.89) (Table 3).

Discussion
This study was designed to evaluate HPV prevalence
and genotypic pattern during normal pregnancy and
post-partum. The results revealed that overall infection
with HPV and with high-risk HPV genotypes is
highest during the second trimester of pregnancy.
Among the high-risk HPV genotypes, infection with
HPV 16 or 18 is seen most commonly during the third
trimester of pregnancy.
A number of studies have suggested that pregnancy
may increase susceptibility to HPV infection. In one
publication from Mexico, screening of 274 pregnant
and 1060 age-matched non-pregnant patients showed a
3.5-fold increased risk of high-risk HPV infection
during pregnancy (37.2% vs 14.2%).7 A similar study
from Turkey confirmed a higher prevalence of HPV
infection (29.2% vs 19.6%) and high-risk HPV genotypes (14.6% vs 9.6%) among pregnant compared with
non-pregnant women.15 The current study in a Korean

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Journal of Obstetrics and Gynaecology Research 2013 Japan Society of Obstetrics and Gynecology

203

204
0.01

0.04

0.04

<0.01

1.00
0.67 (0.490.92)#

1.00
0.82 (0.561.20)
0.73 (0.421.29)

1.00
0.72 (0.331.56)
0.69 (0.321.48)
0.50 (0.221.15)

1.00
1.84 (1.242.75)#
1.06 (0.691.63)
1.32 (0.832.09)

HPV
OR (95% CI)

0.35

0.41

0.12

0.04

0.06

1.00
0.72 (0.471.12)
0.64 (0.341.20)

1.00
1.94 (1.233.05)#
1.27 (0.782.07)
1.41 (0.822.44)

High-risk genotypes
OR (95% CI)

0.01

0.05

0.34

0.06

0.03

0.21

1.00
2.84 (1.246.54)#

1.00
1.52 (0.613.77)
0.46 (0.063.75)

1.00
2.88 (0.8210.11)
4.51 (1.3515.04)#
0.88 (0.213.72)

Genotypes 16 or 18
OR (95% CI)

0.03

0.28

0.50

0.03

0.14

0.29

1.00
0.63 (0.420.96)#

Low-risk genotypes
OR (95% CI)

0.44

0.48

0.26

0.03

0.01

0.40

1.00
0.49 (0.270.90)#

1.00
0.57 (0.301.10)
0.12 (0.020.89)#

Multiple infection
OR (95% CI)

0.34

Pearson c2-test. c2-Test for trend. Adjusted for stage of pregnancy, age, parity, education (logistic regression analysis). Adjusted for stage of pregnancy, parity (logistic regression
analysis). Adjusted for stage of pregnancy, parity and number of previous partners (logistic regression analysis). Adjusted for parity, education (logistic regression analysis).
#P < 0.05. CI, confidence interval; HPV, human papillomavirus; OR, odds ratio.

No. of previous partners

1
0.13
2

Age at sexual debut (years)

20
0.28
2123
24

Education
High school
College

Parity
0
1
2

Age (years)
24
2529
3034
35

Stage of pregnancy
First trimester
Second trimester
Third trimester
Post-partum

Characteristic

Table 3 Univariate and multivariable analysis for HPV infection in pregnancy

Y. H. Kim et al.

2013 The Authors

Journal of Obstetrics and Gynaecology Research 2013 Japan Society of Obstetrics and Gynecology

HPV infection during normal pregnancy

population did not measure HPV prevalence in the

non-pregnant population (outside of the puerperium);
however, the prevalence of high-risk HPV infection in
the second trimester in this cohort (23.8%) is indeed
higher than that in historic non-pregnant controls in a
similar population measured in 2010 (15.5% in women
aged 2039 years).16
The reason why HPV infection rates may be more
common in pregnancy than in the non-pregnant state is
not clear. Most HPV infections in young women are
temporary and have little long-term significance.
Indeed, 70% of genital HPV infections are cleared
within 1 year and 90% are cleared in 2 years.17 It has
been proposed that pregnancy may be associated with
immunological changes that make it more difficult for
the body to clear HPV infection.4,6,11 In one such study,
HPV infection persisted in pregnancy but declined significantly in the post-partum period.4
However, not all studies have confirmed an
increased risk of HPV infection in pregnancy,9,18 and
yet other reports have suggested that the clearance of
HPV infection is not different between pregnant and
non-pregnant patients.10,19 As such, the association
between HPV infection and pregnancy remains controversial. We propose that this apparent contradiction in
the literature may be due in part to the fact that HPV
prevalence rates change throughout gestation, a fact
that is not accounted for in these prior publications.
Indeed, few studies have examined HPV infection rates
at different gestational ages. In one study of 213 pregnant Lithuanian women, the HPV prevalence rate was
17.8% in the first trimester and 10.3% in the third trimester (although the second trimester was not examined).20 A recent longitudinal study performed in
Uganda reported that HPV prevalence was unchanged
in the first/second versus third trimesters of pregnancy.10 However, this study was underpowered (with
only 105 pregnant patients), the baseline prevalence of
HPV (60%) and HIV (7.3%) were very high, and a large
number of cases were lost to follow-up, all of which
makes interpretation of these results tentative.
The current cross-sectional study showed that the
rate of high-risk HPV detection was significantly
elevated during the second trimester of pregnancy and
decreased thereafter. However, the most virulent highrisk HPV genotypes, 16 and 18, were seen most frequently in the third trimester (Table 2; Fig. 1). One
possible explanation is that the immunological and/or
hormonal changes in pregnancy may make it more
difficult for the body to clear HPV genotypes 16 and 18
as compared with other HPV genotypes, thereby

allowing these genotypes to persist into the latter stage

of pregnancy.20 The reason why HPV-DNA detection
was more common during the second trimester of
pregnancy in the current study remains unresolved.
Although compromised cell-mediated immunity could
explain an elevated HPV prevalence in pregnancy,21,22 it
is still unclear whether the mechanism involves reactivation of latent HPV infection or new HPV infection.
Efforts to address this question by controlling for
sexual behavior and extramarital affairs have not to
date been successful. Further immunological and
behavioral studies are needed to investigate the reason
behind the different susceptibility to HPV infection in
relation to the stage of pregnancy.
The limitations of our study relate primarily to study
design. A cross-sectional study design inherently limits
the ability of investigators to draw firm conclusions
about the causal relationship between pregnancy and
HPV infection. Although we did not include nonpregnant women as a control group, we were able to
use HPV prevalence data from a recent epidemiological
study of non-pregnant Korean women published in
2010.16 In an effort to mitigate these limitations, we
enrolled a large number of pregnant women, including
a reasonable number at each trimester and postpartum, and used multivariable logistic regression
analysis to adjust for various risk indicators of HPV
infection including sociodemographic, reproductive
and sexual factors.
In conclusion, the current study suggests that the
second trimester of pregnancy may be associated with
cervical HPV infection, especially infection with highrisk HPV genotypes. Further studies should be followed to confirm this specific pattern of HPV
infections, and to estimate the impact of HPV infections
during the pregnant period and thereafter.

Acknowledgment
This study was supported by the Basic Science Research
Program through the National Research Foundation of
Korea (NRF) funded by the Ministry of Education,
Science and Technology (20090074892), Korea.

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Appendix 1 Risk for HPV infection according to sociodemographic characteristics

High-risk genotypes
OR
95% CI

Type 16 and 18
OR
95% CI

Low-risk genotypes
OR
95% CI

Multiple infection
OR
95% CI

1.00
0.372.17
0.311.76
0.221.46
c2 for trend, P = 0.06

1.00
0.40
0.111.51
0.51
0.141.80
0.23
0.051.06
c2 for trend, P = 0.21

1.00
0.37*
0.150.88
0.36*
0.160.85
0.35*
0.140.88
c2 for trend, P = 0.29

1.00
0.55
0.152.01
0.41
0.111.47
0.53
0.132.05
c2 for trend, P = 0.40

Education (years)
12
1.00
1316
0.66*
0.480.90
17
0.71
0.381.34
2
c for trend, P = 0.02*

1.00
0.75
0.521.07
0.57
0.261.26
2
c for trend, P = 0.07

1.00
0.57
0.291.12
0.25
0.031.93
2
c for trend, P = 0.06

1.00
0.63*
0.400.98
0.93
0.412.10
2
c for trend, P = 0.11

1.00
0.56
0.301.05
0.23
0.031.72
2
c for trend, P = 0.03*

Alcohol
Never
Ever

1.00
0.84

0.511.40

1.00
0.61

0.321.17

1.00
0.99

0.342.86

1.00
1.01

0.502.01

1.00
0.43

0.101.80

Smoking
Never
Ever

1.00
1.18

0.831.70

1.00
0.95

0.621.46

1.00
1.38

0.652.92

1.00
1.33

0.812.16

1.00
1.43

0.722.85

Previous Pap
Never
1.00
Ever
0.81

0.591.11

1.00
0.74

0.521.06

1.00
0.56

0.291.08

1.00
0.82

0.531.28

1.00
0.58

0.311.07

OR

HPV
95% CI

Maternal age (years)

24
1.00
2529
0.48
0.231.01
3034
0.46*
0.220.94
35
0.34*
0.160.74
c2 for trend, P = 0.04*

Logistic regression analysis and c -test for trend. *P < 0.05. Reference category. CI, confidence interval; HPV, human papillomavirus; OR, odds ratio.
2

206

2013 The Authors

Journal of Obstetrics and Gynaecology Research 2013 Japan Society of Obstetrics and Gynecology

HPV infection during normal pregnancy

Appendix 2 Maternal age-adjusted risk for HPV infections according to demographic

and reproductive characteristics
HPV
95% CI

OR
Age at menarche (years)
14
1.00
15
0.98

0.731.33

High-risk genotypes
OR
95% CI

Genotypes 16 and 18
OR
95% CI

Low-risk genotypes
OR
95% CI

Multiple infection
OR
95% CI

1.00
0.99

1.00
1.35

1.00
1.01

1.00
1.24

0.701.41

0.702.60

0.661.54

0.672.27

Age at marriage (years)

24
1.00
2529
1.41
0.722.77
30
1.50
0.733.08
c2 for trend, P = 0.68

1.00
1.37
0.642.92
1.12
0.492.54
c2 for trend, P = 0.18

1.00
0.50
0.171.45
0.45
0.131.48
c2 for trend, P = 0.11

1.00
1.88
0.635.59
2.66
0.848.42
c2 for trend, P = 0.53

1.00
1.18
0.324.32
0.98
0.244.04
c2 for trend, P = 0.58

Age at first pregnancy (years)

24
1.00
2529
0.78
0.481.25
30
0.74
0.451.22
2
c for trend, P = 0.08

1.00
0.86
0.501.45
0.66
0.371.17
2
c for trend, P = 0.03*

1.00
0.51
0.191.38
0.84
0.302.31
2
c for trend, P = 0.62

1.00
0.74
0.371.48
1.09
0.532.22
2
c for trend, P = 0.81

1.00
0.88
0.322.42
1.14
0.393.33
2
c for trend, P = 0.77

1.00
0.72
0.491.04
0.73
0.401.32
c2 for trend, P = 0.04*

1.00
0.72
0.361.42
0.17
0.021.32
c2 for trend, P = 0.03*

1.00
0.90
0.581.41
0.56
0.251.25
c2 for trend, P = 0.14

1.00
0.57
0.291.11
0.11*
0.010.87
c2 for trend, P = 0.01*

No. of births
0
1
2

1.00
0.79
0.571.09
0.75
0.451.26
c2 for trend, P = 0.04*

Spontaneous abortion
Never
1.00
Ever
0.71

0.461.11

1.00
0.68

0.401.16

1.00
1.07

0.432.61

1.00
0.89

0.491.62

1.00
0.86

0.352.10

Induced abortion
Never
Ever

1.00
1.16

0.811.65

1.00
1.32

0.891.97

1.00
0.96

0.432.12

1.00
0.77

0.451.33

1.00
0.67

0.291.53

Stage of pregnancy
First trimester
Second trimester
Third trimester
Post-partum

1.00
1.94*
1.15
1.16

1.322.87
0.761.74
0.761.76

1.00
2.13*
1.41
1.21

1.363.33
0.882.27
0.741.98

1.00
1.83
2.67*
0.75

0.764.41
1.196.01
0.232.39

1.00
1.40
0.88
1.08

0.822.40
0.481.60
0.611.91

1.00
1.64
1.47
0.80

0.753.58
0.663.27
0.302.09

Logistic regression analysis and c2-test for trend. *P < 0.05. Reference category. CI, confidence interval; HPV, human papillomavirus; OR, odds ratio.

Appendix 3 Maternal age-adjusted risk for HPV infections according to sexual

indicators and contraceptive methods
Type 16 or 18
OR
95% CI

OR

1.00
1.57
0.982.52
0.89
0.511.54
2
c for trend, P = 0.41

1.00
1.33
0.493.63
0.76
0.262.28
2
c for trend, P = 0.34

1.00
1.36
0.712.62
0.89
0.451.76
2
c for trend, P = 0.50

1.00
0.89
0.352.26
0.78
0.302.05
2
c for trend, P = 0.26

No. of previous sexual partners

1
1.00
2
1.35
0.951.92

1.00
1.23

1.00
2.40*

1.00
1.33

1.00
1.36

Husbands extramarital affair

No
1.00
Uncertain 1.16
0.711.90
Possible
1.31
0.256.90
c2 for trend, P = 0.64

1.00
0.88
0.481.61
0.87
0.107.36
c2 for trend, P = 0.57

1.00
1.08
0.363.21
4.63
0.5240.98
c2 for trend, P = 0.51

1.00
1.51
0.822.79
1.38
0.1611.71
c2 for trend, P = 0.21

1.00
1.40
0.563.53

c2 for trend, P = 0.81

Contraception
None
OCP
Condom
IUD

1.00
1.49
0.80
0.38

1.00
1.19
1.27
2.49

1.00
1.14
0.86
0.51

1.00
2.13
0.44
1.11

OR
Age at sexual
20
2123
24

HPV
95% CI

debut (years)
1.00
1.27
0.792.07
0.93
0.571.53
2
c for trend, P = 0.28

1.00
1.19
0.92
0.50

0.662.14
0.621.34
0.112.32

OR

High-risk
95% CI

0.821.86

0.792.83
0.511.26
0.053.02

1.065.42

0.314.54
0.543.00
0.2822.21

Low-risk
95% CI

0.822.15

0.532.47
0.511.44
0.064.07

Multiple infection
OR
95% CI

0.672.76

0.855.35
0.191.03
0.139.38

Logistic regression analysis and c2-test for trend. *P < 0.05. Reference category. CI, confidence interval; IUD, intrauterine device; OCP, oral contraceptive
pill; OR, odds ratio.

2013 The Authors

Journal of Obstetrics and Gynaecology Research 2013 Japan Society of Obstetrics and Gynecology

207