Publication of the International Union Against Cancer

Int. J. Cancer: 107, 811 816 (2003)

2003 Wiley-Liss, Inc.

CONDOM USE PROMOTES REGRESSION OF CERVICAL INTRAEPITHELIAL

NEOPLASIA AND CLEARANCE OF HUMAN PAPILLOMAVIRUS:
A RANDOMIZED CLINICAL TRIAL
Cornelis J.A. HOGEWONING1, Maaike C.G. BLEEKER2, Adriaan J.C. VAN DEN BRULE2, Feja J. VOORHORST3, Peter J.F. SNIJDERS2,
Johannes BERKHOF3, Pieter J. WESTENEND4 and Chris J.L.M. MEIJER2*
1
Department of Gynaecology and Obstetrics, Albert Schweitzer Hospital, Dordrecht, the Netherlands
2
Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands
3
Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands
4
Department of Pathology, Albert Schweitzer Hospital, Dordrecht, the Netherlands
Women with persistent HPV infections have increased risk
of progressive CIN lesions. Transmission of HPV between
sexual partners might maintain viral infection and, consequently, may inuence the clinical course of CIN. We investigated the effect of condom use on regression of CIN lesions
and on clearance of HPV. Women with CIN and their male
sexual partners were randomized for condom use (condom
group n 72 and noncondom group n 76). They were
conservatively managed and followed every 3 6 months by
colposcopy, cytology and HPV testing by GP5/6 PCR.
Baseline cervical biopsy specimens were taken. Median follow-up time for women was 15.2 months (range 3.0 85.4).
Outcomes of interest were clinical regression of CIN at colposcopy and clearance of HPV. Outcomes were assessed in
64 women of the condom group and 61 women of the noncondom group. Women in the condom group showed a
2-year cumulative regression rate of 53% vs. 35% in the noncondom group (p 0.03). The 2-year cumulative rates of
HPV clearance were 23% vs. 4%, respectively (p 0.02).
Although lower regression rates were found if women were
HPV-positive and had >CIN2 lesions at baseline, effects of
condom use were found both in women with CIN1 and in
women with >CIN2 lesions. Condom use promotes regression of CIN lesions and clearance of HPV.
2003 Wiley-Liss, Inc.
Key words: cervical intraepithelial neoplasia; human papillomavirus; condom use; clinical course

Persistent infection of the cervical epithelium with high-risk

types of HPV plays a major role in the development, maintenance
and progression of CIN.1,2 HPV has been found in 99.7% of
cervical cancers worldwide.3
Sexual intercourse is the primary mode for transmission or
acquisition of HPV, and prevalence is related to many determinants involving sexual behavior characteristics.4 6 Case-control
studies of male sexual partners of women with cervical cancer
have shown a relation between male sexual behavior and cervical
cancer.7,8 The presence of HPV DNA in penile swabs conveyed a
5-fold risk of cervical cancer to their wives.5 Studies on the risk
factors of CIN supported a protective effect of condom use in
women, emphasizing the venereal nature.9 11 Coker et al.12 found
that among high-risk HPV-positive women longer-duration barrier
method use was associated with a reduced risk of CIN. Manhart
and Koutsky13 reported in a meta-analysis that data on effects of
condom use preventing HPV infection and HPV-related conditions
were inconsistent. However, none of these studies was conducted
explicitly to assess the effectiveness of condoms at preventing
HPV infection and HPV-related conditions.
Previously, we showed that at penile lesions are associated
with the presence of HPV and that regression is dependent on the
presence of HPV14 (see also Bleeker and Hogewoning, 2003,
accompanying paper). Continuous transmission of HPV in sexual
partners having HPV-associated genital lesions might reduce the
chance of viral clearance. In a randomized clinical trial, we investigated the inuence of condom use on the clinical course of

HPV-associated genital lesions and HPV infection in sexual partners. In the present report, we evaluate the effects of condom use
on CIN regression and HPV clearance.
MATERIAL AND METHODS

Study population and design

Women referred to the colposcopy clinic of the Albert
Schweitzer Hospital, Dordrecht, the Netherlands, from January
1995 to June 2002 were asked to bring in their male sexual partner.
Eligible were women with an abnormal cervical smear (mild
dysplasia or worse) and/or cCIN and/or hCIN. Women were evaluated for CIN by colposcopy and by histologic evaluation of
cervical biopsy specimens at baseline. Cervical smears were taken
for cytology and HPV testing by PCR. The outline of the study was
verbally explained and written information given to couples who
had no other sexual partners. Willing couples returned within 2
weeks to discuss the study protocol in detail, and additional questions were answered. Both the period of condom use, i.e., only
during the study and for at least 3 months, and the instructions on
condom use, i.e., during genital genital contact, were discussed
with participants. Latex condoms (Durex fetherlite; Netherlands
LRC, Leerdam, the Netherlands) with basic lubricant (without
spermicidal and/or virus-inactivating substances) were given free,
to increase study compliance. Exclusion criteria were surgical
treatment of the cervical lesion and regular condom use at baseline,
i.e., using condoms for birth control. CIN2 and CIN3 lesions over
Abbreviations: cCIN, colposcopicly cervical intraepithelial neoplasia;
CI, condence interval; CIN, cervical intraepithelial neoplasia; EIA, enzyme immunoassay; hCIN, histologicly cervical intraepithelial neoplasia;
HPV, human papillomavirus; HR, hazard ratio; LLETZ, large-loop biopsy
of the entire transformation zone; STD, sexually transmitted disease.
Grant sponsor: Dutch Prevention Fund/Zorg Onderzoek Nederland;
Grant number: 28-2725.
This work is dedicated to Jan M.M. Walboomers, who passed away on
2 February 2000. He was one of the principal investigators of this project.
The rst 2 authors contributed equally to this work.
*Correspondence to: Department of Pathology, VU University Medical
Center, PO Box 7057, 1007 MB, Amsterdam, the Netherlands.
Fax: 31-020-444-2964. E-mail: cjlm.meijer@vumc.nl
Received 13 March 2003; Revised 1 July 2003; Accepted 18 July 2003
DOI 10.1002/ijc.11474

812

HOGEWONING ET AL.

FIGURE 1 Trial prole.

2 cervical quadrants were treated according to standard protocols. Irrespective of CIN grade at baseline, couples were randomized for condom use in blocks of 2 if conservative management of
the CIN lesion was decided. Per block of 2 couples, the sequence
of condom and noncondom allocation was based on a table of
random numbers. Colposcopic and cervical smears were repeated
after 3, 6 and 12 months and subsequently every 6 months.
Condom use was verbally veried at each visit by asking the
frequency of condom use failure. To minimize interference with
the natural course of CIN, a biopsy specimen was taken during
follow-up only when progression of CIN lesions was suspected on
the basis of ndings at colposcopy and/or cytology to justify the
LLETZ procedure. Follow-up was ended if women were treated by
LLETZ. Couples were asked to complete a questionnaire on lifestyle habits, including sexual behavior. Independently of each
other and in separate rooms, questionnaires were completed. This
questionnaire was introduced in 1999. The study protocol was
approved by the ethics review board of the hospital (protocol
CGE/95/238), and the couples signed informed consent before
enrollment.
Colposcopy
Before colposcopic evaluation, cervical smears were taken for
cytologic and HPV testing. For HPV testing, a Cervex brush
(Rovers Medical Devices, Oss, the Netherlands) was used to
collect cells from the cervix. The brush was placed in 5 ml of PBS
solution with 0.001% thimerosal (Merthiolate) (BDH, Poole, UK),
and samples were sent to the laboratory and stored at 4C until
testing.15 Standard colposcopy was performed after application of
3% acetic acid solution and blinded of data from previous visits.
Colposcopic characteristics such as acetowhiteness, mosaic, punctation, leukoplakia and atypical vessels were assessed and classied according to the international terminology.16 Minor changes,

e.g., thin acetowhite epithelium, ne mosaic, ne punctation and

thin leukoplakia, were noted as cCIN1 and major changes, e.g.,
dense acetowhite epithelium, coarse mosaic, coarse punctation and
atypical vessels, as cCIN2 or cCIN3. Other diagnoses, e.g., squamous metaplasia, inammatory changes, polyps or atrophic
changes, were also noted. An overview of the colposcopic impression was drawn and categorized on the basis of the most atypical
site: no cCIN, cCIN1, cCIN2 and cCIN3. Subsequently, colposcopic ndings were documented by photographs. Photographs
were reviewed by an experienced colposcopist blinded of any
clinical data. In case of discrepancies (10%), a consensus diagnosis was made. Lesions were graded before linking these data on
condom use.
HPV testing
Processing and testing of cervical scrapings for HPV analysis
were performed as described previously at the Department of
Pathology, VU University Medical Center.15 Samples were centrifuged and cell pellets resuspended in 1,000 l TRIS buffer. In
PCR tests, aliquots of 10 l were used. The quality of the specimen was tested by -globin PCR, and 14 high-risk (16, 18, 31, 33,
35, 39, 45, 51, 52, 56, 58, 59, 66 and 68) and 6 low-risk (6, 11, 40,
42, 43 and 44) HPV genotypes were identied by the clinically
validated HPV GP5/6 PCR EIA. Samples negative on both the
-globin and HPV PCR tests were considered inadequate and
excluded.
Definitions of CIN regression and HPV clearance
Regression of the cCIN lesion was dened as 2 consecutive no
cCIN diagnoses at colposcopy. Women were considered to have
cleared the HPV infection when 2 consecutive negative HPV tests
were obtained.

CONDOM USE AND CIN REGRESSION/HPV CLEARANCE

813

Statistical analysis
Analyses for condom use were by intention to treat. Differences
between the condom and the noncondom groups were assessed by
2 tests or independent t-tests. In survival analysis, the time point
of CIN regression and HPV clearance was taken as the midpoint
between the last positive and the rst negative results. KaplanMeier curves, for regression of cCIN lesions and clearance of
HPV, were compared by means of 2-sided log-rank tests. Cox
regression analyses were performed to calculate the HR and 95%
CI, adjusted for condom use, HPV status, histologic CIN grade
(either hCIN1 or hCIN2) and age (tertiles). HPV status was
dened by the presence of HPV at baseline. HPV-positive women
were stratied into HPV-16, other high-risk HPV or only low-risk
HPV to assess whether CIN regression and/or HPV clearance was
related to HPV type. Interaction terms were added to the Cox
model to assess whether the effect of condom use was related to
HPV status or the hCIN grade of the lesions. Within the condom
group, whether the effect was dependent on the duration of condom use was assessed. Therefore, Kaplan-Meier analyses were
performed on women who still had colposcopic CIN or HPV
present at 6 months and were stratied for condom use at this time
point. Statistical signicance was set at the 0.05 level. For statistical analyses, SPSS (Chicago, IL) version 9.0 software was used.
RESULTS

Characteristics of the study population

The trial prole is given in Figure 1. Of 255 couples selected for
the presence of CIN in the female partner, 17 were not willing to
participate, 78 women were treated by LETTZ and 12 women were
excluded due to regular condom use, leaving 148 women randomized (condom group n 72 and noncondom group n 76).
Women were excluded because of no colposcopic CIN (n 9), no
colposcopic diagnosis (n 4) or loss to follow-up (n 10). The
remaining 125 women were followed: 64 in the condom group and
61 in the noncondom group. Median follow-up time was 16.4
(range 3.0 85.4) months in the condom group and 12.8 (range
3.1 63.0) months in the noncondom group. Median duration of
condom use was 6.0 (range 3.0 53.7) months, and failure to use
condoms was reported by 7 women with a median of 2 times
during the period of condom use (range 15). Characteristics of
both groups are shown in Table I. At baseline, colposcopic diagnoses were, in the condom group, cCIN1 (n 34), cCIN2 (n 29)
and cCIN3 (n 1) and, in the noncondom group, cCIN1 (n 36),
cCIN2 (n 24) and cCIN3 (n 1). Representative histologic
diagnoses of biopsy specimens were not available in 6 (9%)
women of the condom group and 4 (7%) women of the noncondom
group. Eight of them had cCIN1 lesions and 2 had a cCIN2 lesion.
The remaining biopsies showed, in the condom group, no hCIN in
8 (14%), hCIN1 in 18 (31%), hCIN2 in 31 (53%) and hCIN3 in 1
(2%) and, in the noncondom group, no hCIN in 11 (19%), hCIN1
in 25 (44%), hCIN2 in 19 (33%) and hCIN3 in 2 (4%). Histologic
evaluation of cCIN1 lesions (n 62) showed no hCIN in 13
(21%), hCIN1 in 31 (50%), hCIN2 in 17 (27%) and hCIN3 in 1
(2%) biopsy specimens. Histologic evaluation of cCIN2 lesions
(n 51) showed no hCIN in 6 (12%), hCIN1 in 11 (22%), hCIN2
in 32 (63%) and hCIN3 in 2 (4%) biopsy specimens. The 2 women
with cCIN3 were included in the study because histologic specimens showed hCIN1 and hCIN2, respectively. Three women with
hCIN3 lesions were included because their lesions were small (2
cervical quadrants). At baseline, 2/64 (3%) cervical scrapes of the
condom group and 2/61 (3%) cervical scrapes of the noncondom
group were inadequate for HPV testing, i.e., were negative in both
the -globin and HPV PCR tests. Of the remaining, 101 (84%)
scrapes were positive for HPV: 54 (87%) of the condom group and
47 (80%) of the noncondom group. Of the HPV-positive women,
HPV-16 was found in 27 (50%) of the condom group and in 22
(47%) of the noncondom group and other high-risk HPV (not
HPV-16) was found in 26 (48%) and 22 (47%), respectively. Only

FIGURE 2 Effect of condom use on regression of CIN lesions (a)

and clearance of HPV (b).

low-risk HPV was found in 1 (2%) HPV-positive woman of the

condom group and in 3 (6%) HPV-positive women of the noncondom group. Questionnaires were obtained from 51/125 (41%)
women, 26/64 (41%) of the condom group and 25/61 (41%) of the
noncondom group. No statistical differences were found between
the condom and noncondom groups for smoking habits, age at rst
sexual intercourse, number of sexual partners, number of noncondom sexual partners, history of STDs, other sexual partners last
year, duration of the current relation, frequency of sexual intercourse and contraceptive use (Table I).
Regression of CIN
The 2-year cumulative regression rate of cCIN was 53% in the
condom group (n 57) vs. 35% in the noncondom group (n 51,
log rank p 0.03; HR 3.1, 95% CI 1.4 7.1) (Fig. 1, Table II).
Since regression was dened as 2 consecutive no cCIN diag-

814

HOGEWONING ET AL.
TABLE I CHARACTERISTICS OF THE STUDY POPULATION

Study subjects
Age (mean, range, in years)
30.8
30.836.4
36.4
Follow-up time (median, range, in months)
HPV at baseline
Positive
HPV-16
Other high-risk HPV (not HPV-16)
Only low-risk HPV
Negative
ND1
CIN grade at colposcopy
CIN1
CIN2
CIN3
CIN grade at histology
No biopsy
No CIN
CIN1
CIN2
CIN3
Characteristics obtained by questionnaires
Study subjects
Smoking
No
Yes
Years (mean, range)
Cigarettes per day (mean, range)
Oral contraceptive use
No
Yes
Age at rst sexual intercourse (years, mean, range)
History of STD
No
Yes
Lifetime sexual partners
Overall (mean, range)
Noncondom partners (mean, range)
Other sexual partner last year
No
Yes
Type of relationship
Married/living together
Living apart
Duration relation in years (mean/range)
Frequency sexual Intercourse
Frequency per month (mean, range)
Frequency last month (mean, range)

Number (%)

Condom group
Number (%)

Noncondom group
Number (%)

125
34.6 (19.154.7)
42 (34)
41 (33)
42 (34)
15.2 (3.085.4)

64 (51)
34.1 (19.154.7)
21 (33)
23 (36)
20 (31)
16.4 (3.085.4)

61 (49)
35.1 (22.552.6)
21 (34)
18 (30)
22 (36)
12.8 (3.163.0)

101 (84)
49 (49)
48 (48)
4 (4)
20 (17)
4

54 (87)
27 (50)
26 (48)
1 (2)
8 (13)
2

47 (80)
22 (47)
22 (47)
3 (6)
12 (20)
2

70 (56)
53 (42)
2 (2)

34 (53)
29 (45)
1 (2)

36 (59)
24 (39)
1 (2)

10
19 (17)
43 (37)
50 (43)
3 (3)

6
8 (14)
18 (31)
31 (53)
1 (2)

4
11 (19)
25 (44)
19 (33)
2 (4)

51 (41)

26 (41)

25 (41)

25 (49)
26 (51)
18.7 (735)
16.2 (230)

16 (62)
10 (38)
17.0 (1025)
15.2 (230)

9 (36)
16 (64)
19.5 (735)
16.8 (530)

23 (45)
28 (55)
16.3 (1321)

14 (54)
12 (46)
16.3 (1321)

9 (36)
16 (64)
16.2 (1321)

45 (88)
6 (12)

24 (92)
2 (8)

21 (84)
4 (16)

5.9 (130)
3.9 (110)

5.6 (115)
4.3 (110)

6.3 (130)
3.6 (110)

49 (96)
2 (4)

24 (92)
2 (8)

25 (100)
0 (0)

46 (90)
5 (10)
9.2 (0.635)

24 (92)
2 (8)
9.7 (0.635)

22 (88)
3 (12)
8.7 (128)

0.7

7.2 (022.5)
5.5 (020)

7.2 (022.5)
4.6 (020)

7.2 (122.5)
6.4 (120)

1.0
0.2

0.9
0.7
0.4
0.6
0.3
0.5

0.3

0.2

1.0
0.1
0.5
0.6
0.3
0.7
0.4

0.6
0.3
0.5
0.7

1
Not be determined due to samples being inadequate for HPV testing. CIN grade (at colposcopy and histology) refers to diagnoses made at
baseline.

noses, 17 women were excluded due to lack of follow-up data after

they showed a normal colposcopy once. Age was not related to
regression of CIN in our study population. Less regression of cCIN
was seen in HPV-positive women (HR 0.2, 95% CI 0.1 0.5)
and in women with hCIN2 at baseline (HR 0.3, 95% CI
0.1 0.7). In HPV-positive women, regression of CIN was not
related to HPV type when stratied into HPV-16, other high-risk
HPV or only low-risk HPV. The effect of condom use was not
related to HPV status (p 0.4) or hCIN grade at baseline (p
0.8). Since the outcome variable for regression of cCIN was
dened by colposcopy, analyses were also performed with inclusion of the cCIN grade instead of the hCIN grade dened at
baseline. Less regression of cCIN was observed in women with
cCIN2 compared to women with cCIN1 at baseline (HR 0.3,
95% CI 0.1 0.6, p 0.003). In women who still had cCIN lesions
at 6 months, no different regression rates were found during
follow-up to 24 months in those who used condoms longer than 6

months (n 14) compared to those who used condoms for less

than 6 months (n 15; log-rank p 0.6).
Clearance of HPV
The 2-year cumulative rate of HPV clearance was 23% in the
condom group (n 53) vs. 4% in the noncondom group (n 38,
log rank p 0.02; HR 12.1, 95% CI 1.597.2) (Fig. 2, Table II).
Of the 125 women, 34 were excluded in the HPV clearance
analyses since they were HPV-negative at baseline (n 20), they
had cervical scrapes that were inadequate for HPV testing at
baseline and/or during follow-up (n 7) or there was no available
follow-up data on HPV after they were HPV-negative once (n
7). No relation was found between clearance of HPV and age.
Clearance of HPV was related to hCIN grade; i.e., less HPV
clearance was found in women with hCIN2 compared to women
with hCIN1 at baseline (HR 0.2, 95% CI 0.04 0.8). However,
HPV clearance was not related to cCIN grade at baseline (HR

815

CONDOM USE AND CIN REGRESSION/HPV CLEARANCE

TABLE II PROGNOSTIC FACTORS FOR CIN REGRESSION AND HPV CLEARANCE
CIN regression
Number

Condom use
No
Yes
HPV
Negative
Positive
HPV-16
Other high-risk HPV (not HPV-16)
Only low-risk HPV
Histologic CIN grade
CIN1
CIN2
Age (years)
30.8
30.836.4
36.4

HR (95% CI)

HPV clearance
p

Number

HR (95% CI)

36
48

1.0
12.1 (1.597.2)

0.01

0.6
0.6

44
37
3

NA
NA
1.0
3.1 (0.614.6)
01

0.2
1.0

48
50

1.0
3.1 (1.47.1)

13
85
44
38
3

1.0
0.2 (0.10.5)
1.0
1.3 (0.53.5)
2.0 (0.032.3)

48
50

1.0
0.3 (0.10.7)

0.01

38
46

1.0
0.2 (0.040.8)

0.02

30
35
33

1.0
1.6 (0.64.3)
1.3 (0.53.6)

0.3
0.6

27
28
29

1.0
0.4 (0.044.0)
2.9 (0.811.7)

0.4
0.1

0.006
0.0003

Adjustments were made for all other factors in the table. NA, not applicable.1Could not be calculated since no clearance was observed in
this category.

0.4, 95% CI 0.11.7). In HPV-positive women, HPV clearance

was not related to HPV type when stratied into HPV-16, other
high-risk HPV or only low-risk HPV. hCIN grade at baseline
histology was not related to the effect of condom use on HPV
clearance (p 0.9). In women who still were HPV-positive after
6 months, no different clearance rates were found in those who
used condoms longer than 6 months (n 17) compared to those
who used condoms for less than 6 months (n 14, log-rank p
0.6).
DISCUSSION

In a randomized clinical study, performed in a non-STD clinic,

125 women with cCIN were followed by colposcopy and HPV
testing. We found that condom use promotes regression of cCIN
and clearance of HPV. The 2-year cumulative regression rate for
cCIN was 53% in the condom group vs. 35% in the noncondom
group (p 0.03), and 2-year cumulative rates of HPV clearance
were 23% vs. 4%, respectively (p 0.02). These benecial effects
of condom usage were independent of hCIN grade.
One limitation of our study was that regression of CIN was
dened by colposcopy and not veried by histology. Only baseline
biopsy specimens were taken for histopathologic diagnoses since
repeated biopsies would interfere too much with the natural course
of the CIN lesion. To minimize this potential weakness, regression
of cCIN was dened as disappearance of the total cCIN lesion and
events were scored only in women with 2 consecutive no cCIN
diagnoses. Our ndings on concordance between the colposcopic
and histopathologic diagnoses are in agreement with the positive
predictive rates reported by Hopman et al.17 They reported positive
predictive rates of the colposcopic impression to be 62% for no
CIN, 43% for CIN1, 59% for CIN2 and 78% for CIN3.
Women with a negative HPV test at baseline showed more
regression of cCIN compared to women who were HPV-positive.
This is in agreement with ndings on the relation between HPV at
baseline and cytologic regression in women with abnormal
smears.18,19 In analogy, a shorter regression time of at penile
lesions was found in the absence of HPV, as reported in the
accompanying paper on male sexual partners of women with CIN.
Another limitation of our study is that the number of women
included is relatively small and women were not randomized by
CIN grade. Compared to the noncondom group, a relatively high
number of women with high-grade CIN were included in the
condom group, which might result in underestimation of the effect
of condoms as the grade of the CIN lesion is an important prognostic factor for the regression of CIN.20 Analyses on the effects of

condoms, however, were adjusted for the most important risk

factors (i.e., CIN grade and HPV status).
As characteristics of sexual behavior were collected in only 41%
of women, adjustments for these factors could not be done properly. However, no differences on sex-related factors between
groups were found, as one would expect given the randomized
design of our study. Moreover, as data collection was time-selected, the women who lled out the questionnaires comprised a
representative sample of the whole population. Therefore, we
conclude that these factors did not inuence our ndings on
condom use. Current sex-related factors, especially frequency of
sexual intercourse, might be relevant to assess the effect of condom use, though no differences were found among the couples
analyzed. However, failure to use condoms, as was found in the
condom branch, might result in a less favorable effect of condom
use on CIN regression and HPV clearance. Benecial effects of
condom use were found after a relatively short duration of use
(median 6.0 months). We used a minimal duration of 3 months
condom use before randomization, though the maximum duration
of condom use was not dened at baseline. An attractive, though
hypothetical, explanation for our ndings might be that condoms
interfere with continuous transmission of shed HPV between sexual partners. As a consequence, in individuals who benet from
this interference, the viral load would remain under a certain
critical threshold, allowing effective virus elimination by the immune system, thereby accelerating regression of the lesion. Noninterference in these individuals would, however, result in viral
load levels that are sufciently high to safeguard viral persistence.
That viral load may be an important determinant in the observed
phenomena is substantiated by another study, which demonstrated
that women with abnormal cytology and relatively low HPV-16
loads had an increased chance of viral clearance and cytologic
regression.21 Since the viral load appears to be proportional to the
size and severity of lesions, a more marked effect of condom use
is expected for smaller, less severe lesions that consequently have
lower viral loads.22 Indeed, the effect was much more pronounced
for penile than for cervical lesions. The former are generally
smaller and less severe and have viral loads that are 5- to 10-fold
lower than in their cervical counterparts (data not shown). In
contrast, individuals with high viral loads are unlikely to respond
to condom use since maintenance of the lesion would not depend
on exposure to virus of the partner. Because women with large and
severe lesions (cCIN2 on 2 quadrants) were treated for ethical
reasons, only women with relatively small lesions, having most
likely lower viral load values, were selected for study. Therefore,
an attractive subject of future studies may be to determine the HPV

816

HOGEWONING ET AL.

load by quantitative PCR methods, to further understand the mechanisms underlying the effect of condom use on male and female
HPV-associated lesions.
In conclusion, although this is a relative small study, it demonstrates that intervention with condom use for at least 3 months can
promote CIN regression and HPV clearance. Our results imply that
condom use should be considered as an alternative strategy in the
management of women with CIN and that the need for aggressive
treatments may be reduced. Condom use should also be advised in
pregnant women with CIN, in whom treatment is difcult.

Whether condom use might be helpful in decreasing the number of

latent HPV infections in HPV-positive cytologically normal
women is currently under investigation.
ACKNOWLEDGEMENTS

We thank Mr. R.E. van Andel and Mrs. M.C.G.T. Verkuyten for
technical assistance on HPV testing. We thank Dr. N. Munoz of
the IARC for critical reading of the manuscript and critical remarks.

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