MAJOR ARTICLE

Risk Factors for Cervicitis among Women

with Bacterial Vaginosis
Jeanne M. Marrazzo,1 Harold C. Wiesenfeld,2 Pamela J. Murray,3 Barbara Busse,3 Leslie Meyn,2 Marijane Krohn,2
and Sharon L. Hillier2

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1
Department of Medicine, University of Washington, Seattle; 2Department of Obstetrics, Gynecology, and Reproductive Sciences and Magee-
Womens Research Institute, University of Pittsburgh, and 3Department of Pediatrics, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania

Background. Cervicitis commonly occurs in women with bacterial vaginosis (BV), often without concomitant
chlamydial or gonococcal infection. The risk factors for cervicitis have not been described.
Methods. We characterized the risk factors for cervicitis, which is defined as endocervical mucopurulent
discharge or easily induced bleeding, among women with BV who were 14–45 years of age. Associations between
cervicitis and the characteristics of the subjects, including the presence of specific vaginal bacteria and chlamydial
or gonococcal infection detected by strand displacement assay, were analyzed.
Results. Of 424 women with BV, 63 (15%) had cervicitis. Of these 63 women, only 8 (13%) had chlamydia
or gonorrhea. The risk factors for cervicitis, adjusted for variables, included older age (P ! .001 , for trend), ⭐12
years of education (odds ratio [OR], 2.4 [95% confidence interval {CI}, 1.3–4.6]; P p .006 ), new male sex partner
(OR, 2.7 [95% CI, 1.4–5.4]; P p .004), female sex partner (OR, 6.2 [95% CI, 1.3–28.3]; P p .02 ), recent oral sex
(OR, 2.3 [95% CI, 1.2–4.2]; P p .008), and absence of vaginal H 2O2-producing Lactobacillus species (OR, 2.7;
95% CI, 3.3–5.9; P p .01). No association with cervicitis was seen for current douching or smoking, race, time
since or frequency of intercourse, or presence or quantity of vaginal bacteria other than H 2O2-producing Lacto-
bacillus species.
Conclusions. Cervicitis is common among women with BV and is associated with some risk factors that are
distinct from those associated with endocervical infection with Neisseria gonorrhoeae or Chlamydia trachomatis.
Absence of H2O2-producing lactobacilli may contribute to the development of cervicitis.

Cervicitis is an inflammatory condition of the cervix
that is generally considered to result from infection with
a sexually acquired organism, most commonly Chla-
mydia trachomatis or Neisseria gonorrhoeae. However,
in many women with cervicitis, these organisms are not
detected, even when highly sensitive diagnostic tests are
performed [1–4]. Some investigators have reported an
association between bacterial vaginosis (BV) and cer-
vicitis, independent of concomitant chlamydial and gon-
ococcal infection [2, 5–7]. BV is the most common
Received 29 July 2005; accepted 27 September 2005; electronically published
2 February 2006.
Presented in part: 2003 International Society for Sexually Transmitted Diseases
Research, Ottawa, Canada, 27–31 July 2003 (abstract 197).
Potential conflicts of interest: none reported.
Financial support: National Institutes of Health (grant U01-AI-47785 to S.L.H.).
Reprints or correspondence: Dr. Jeanne M. Marrazzo, Harborview Medical
Center, Div. of Infectious Diseases, 325 Ninth Ave., Mailbox #359931, Seattle,
WA 98104 (jmm2@u.washington.edu).
The Journal of Infectious Diseases 2006; 193:617–24
 2006 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2006/19305-0002$15.00
cause of vaginitis in most clinical settings, and it is
characterized by the overgrowth of commensal anaer-
obic flora relative to the H 2O2–producing Lactobacillus
species that predominate in the healthy vagina [8, 9].
Although BV has been associated with the acquisition
of C. trachomatis and N. gonorrhoeae [10, 11], 3 lines
of evidence support an independent association be-
tween cervicitis and BV. First, BV is strongly associated
with adverse outcomes related to the upper genital tract,
including increased risks of preterm delivery; low birth
weight; postpartum and postabortal endometritis; and,
in nonpregnant women, increased risks of clinically evi-
dent pelvic inflammatory disease and subclinical en-
dometritis [12–16]. Accordingly, the vaginal bacteria
that are associated with BV have been identified (1) in
the endometrium of women with BV and endometritis;
(2) after laparoscopy, in the fallopian tubes of women
with pelvic inflammatory disease; and (3) in the am-
niotic fluid of women with chorioamnionitis [17–20].
These bacteria clearly traverse the endocervical mucous
barrier in women with BV, and they could conceivably

Cervicitis and Bacterial Vaginosis • JID 2006:193 (1 March) • 617

elicit a local inflammatory response as a result. Second, the
inclusion of intravaginal antibiotic therapy for BV in a standard
treatment regimen for cervicitis has been associated with an
enhanced cure rate for cervicitis in 2 small studies [21, 22].
Finally, the observation that cervical shedding of HIV is in-
creased in women with BV provides further evidence to sup-
port the hypothesis that BV itself may have direct effects on
the endocervical mucosa [23, 24].
To further characterize the association between cervicitis and
BV, we assessed the presence of cervicitis among women with
BV. This evaluation occurred at the time of enrollment of
women into a large, randomized, placebo-controlled study of
intravaginal Lactobacillus capsules for the treatment of BV [25].
SUBJECTS, MATERIALS, AND METHODS
Subjects and clinical definitions. The study population com-
prised women 18–45 years of age who were seeking health care
at 3 clinics (a women’s health clinic and a clinic for adolescents
[both located in Pittsburgh, PA] and a clinic for the management
of sexually transmitted diseases [located in Seattle, WA]). After
written, informed consent was obtained from each woman, the
women were interviewed about their medical history. Current
douching and smoking were defined as douching and smoking
that occurred during the month before enrollment, and sexual
practices were assessed by asking subjects to estimate the recent
frequency of and the time to last occurrence of specific behav-
iors. All subjects underwent a standardized physical examina-
tion, including speculum examination and visual inspection and
collection of vaginal fluid for Gram staining, saline microscopic
examination, pH measurement, and KOH preparation. The pres-
ence of BV was required for enrollment in the study, and BV
was diagnosed on the basis of both clinical criteria (i.e., a vaginal
pH 14.5, clue cells that comprised 120% of all vaginal epithelial
cells on saline microscopic examination, an amine odor that
developed on addition of KOH, and homogeneous vaginal dis-
charge) [26] and an abnormal result of Gram staining of vaginal
fluid (Nugent score, ⭓4) [27].
Because this was a clinical trial of a new therapy for BV,
criteria for exclusion from the study included pregnancy, cur-
rent menses, concomitant vulvovaginal candidiasis (defined as
the presence of compatible clinical symptoms and the pres-
ence of yeast forms on KOH preparation of vaginal fluid) or
trichomoniasis (defined by saline microscopic examination of
vaginal fluid performed at the time of examination), use of
intravaginal or systemic antimicrobials during the week before
enrollment, use of any investigational drug during the month
before enrollment, hypersensitivity to metronidazole, the pres-
ence of an intrauterine device, spontaneous or surgical men-
opause, concurrent anticoagulation therapy, and ingestion of
alcohol during the 24 h before enrollment. The conduct of the
study adhered to standard guidelines for research involving hu-
618 • JID 2006:193 (1 March) • Marrazzo et al.
mans, and the study was approved by the human subjects re-
view committees of the University of Washington and the Uni-
versity of Pittsburgh.
Cervicitis was defined as the presence of either mucopurulent
(yellow) endocervical discharge and/or endocervical bleeding
(graded as “moderate” or “severe,” as defined by the clinician)
induced by gentle passage of a cotton swab. Women with cer-
vicitis received standard antibiotic regimens for the treatment
of C. trachomatis and N. gonorrhoeae infection [28] and were
asked to return 1 week after treatment for reevaluation and for
consideration for enrollment into the prospective trial of BV
treatment.
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Microbiological analysis. Vaginal swab specimens from the
lateral vaginal wall were collected and used for aerobic and an-
aerobic cultures, as well as for nucleic acid amplification testing
performed using the strand displacement assay (BDProbeTec)
for C. trachomatis and N. gonorrhoeae [29]. Swab specimens
obtained for culture were immediately placed into Port-a-Cul
anaerobic transport tubes (Becton Dickinson), which were held
and transported at room temperature to the central laboratory
(Magee-Womens Research Institute, Pittsburgh) and were pre-
pared for culture immediately on receipt. Vaginal swab speci-
mens were used to culture aerobic and anaerobic organisms
and genital mycoplasmas by use of a quantitative method, as
described elsewhere [30], focusing particularly on bacteria that
have been consistently associated with BV. Trichomonas vagi-
nalis was cultured using the InPouch TV system (BioMed Di-
agnostics). Lactobacilli were identified to the genus level by
Gram staining; colony morphologic findings; negative results
of a catalase test; and production of lactic acid, as assessed by
gas chromatographic analysis [31]. Lactobacillus isolates were
tested for the production of H 2O2 in a qualitative assay per-
formed on a tetramethylbenzidine agar plate [32]. Organisms
grown anaerobically for 2–3 days were exposed to ambient air.
Colonies of H 2O2-producing organisms form a blue pigment
as horseradish peroxidase reacts with tetramethylbenzidine in
the presence of H 2O2.
Statistical analysis. By use of SPSS statistical software (ver-
sion 10.1.4; SPSS), the association between cervicitis detected
at the enrollment visit and the characteristics of the subjects
was measured by x 2 analysis, the Mann-Whitney U test (for
nonparametric comparisons of continuous variables), and lo-
gistic regression (for multivariable analysis). The characteristics
that were assessed included demographic characteristics, as well
as current smoking and douching, a history of genital herpes,
sexual behavior, current use of hormonal contraception, cur-
rent phase of the menstrual cycle, the presence of cervical ec-
topy, and the detection of individual bacterial species by vagi-
nal cultures. For analysis of the menstrual cycle phase, subjects
were included in the analysis if they reported that menses oc-
curred within the 28 days before enrollment. To define the as-
sociation between cervicitis and vaginal bacteria, we considered
both the presence and the absence of individual species and,
among women colonized with individual species, their absolute
quantity. All tests for statistical significance were 2-sided; P !
.05 denoted statistical significance. Interactions between vari-
ables entered into the multivariable analysis were assessed us-
ing a likelihood ratio test.
RESULTS
A total of 424 women with BV were enrolled in the study; of
these women, 63 (15%) had cervicitis. Cervicitis was defined
by the presence of endocervical mucopurulent discharge in 44
women (70% of women with cervicitis), by easily induced bleed-
ing in 15 women (24%), and by both of these clinical signs in
4 women (6%). Of the 63 women with cervicitis, 4 (6%) had
C. trachomatis and 4 (6%) had N. gonorrhoeae infection, as de-
tected by strand displacement assay; 55 (87%) of the women
had neither of these infections. In addition to the exclusion
criteria noted, none of the subjects had T. vaginalis detected
by culture, clinically evident genital herpes, or any of the cri-
teria for exclusion from the study.
Table 1 displays the univariate relationships between the char-
acteristics of the subjects and the presence of cervicitis. The like-
lihood of cervicitis was higher with increasing age, previous tubal
ligation, report of a higher number of recent male or female sex
partners, report of a new male sex partner, and report of a more
recent episode of receptive oral sex. Women who had used de-
pomedroxyprogesterone acetate (DMPA) in the month before
enrollment or who had cervical ectopy detected at examination
had a lower likelihood of developing cervicitis. No association
was found between reports of current smoking, current douch-
ing, receptive anal sex, infection with C. trachomatis or N. gon-
orrhoeae, or the other risk behaviors noted. The date of the last
menstrual period was available for 321 women (75.9% of all
subjects), of whom 273 reported that the time since their last
menstrual period was ⭐28 days. Detection of cervicitis did not
differ on the basis of whether women were in the menstru-
al phase (2 [13.3%] of 15 subjects), the proliferative phase (12
[10.7%] of 112 subjects), or the secretory phase (25 [17.1%] of
146 subjects) of menses (P p .3).
Table 2 presents details of the comparison of both the qual-
itative presence and the quantity of vaginal bacteria, as detected
by cultivation, between women with and women without cer-
vicitis. The only significant association between cervicitis and
the presence of any individual bacterial species detected in the
vagina was that observed for H 2O2-producing Lactobacillus spe-
cies, which were associated with a lower likelihood of cervicitis
(P p .01). Furthermore, of the women who were colonized
with vaginal H 2O2-producing Lactobacillus species, those who
had cervicitis had significantly lower quantities of these lac-
tobacilli (P ! .001). There was no association between the pres-
ence of individual species alone and cervicitis, but women with
cervicitis had slightly higher quantities of Prevotella bivia than
did women without cervicitis (P p .04).
The risk factors for cervicitis, adjusted for the presence of
C. trachomatis and N. gonorrhoeae and for the other variables,
are displayed in table 3. The characteristics associated with an
increased likelihood of cervicitis included increasing age, ⭐12
years of education, report of a new male sex partner in the
month before enrollment or a female sex partner at the time
of evaluation, and report of receptive oral sex within the week
before enrollment. Vaginal colonization with H 2O2-producing
lactobacilli was associated with a reduced likelihood of cervi-
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citis. In the multivariable model, there was no association be-
tween cervicitis and douching, history of tubal ligation, race,
smoking, presence of cervical ectopy, type of hormonal con-
traception, time to last episode of intercourse, or frequency of
intercourse (data not shown). When individual species of vag-
inal bacteria were assessed in the multivariable model, nei-
ther the presence nor the quantity of any bacteria other than
H 2O2-producing Lactobacillus species was associated with cer-
vicitis (odds ratio [OR] for the absence of H 2O2-producing
Lactobacillus species is shown in table 3; adjusted OR for the
presence of H 2O2-producing Lactobacillus species, 0.4 [95%
confidence interval, 02–0.8]; P p .01).
DISCUSSION
In the present study of 424 women with BV, we found that
cervicitis was relatively common, occurring in 15% of subjects,
and that the overwhelming majority of cervicitis cases (87%)
were not associated with chlamydial or gonococcal infection of
the cervix. None of our subjects was infected with T. vaginalis,
which is a possible cause of cervical inflammation, or had clini-
cal evidence of genital herpes. In addition, among women with
cervicitis, no individual bacterial species associated with BV was
more common or more abundant than the other bacterial spe-
cies noted. Increasing age, fewer years of formal education, report
of a new male sex partner or a current female sex partner, more
recent receptive oral sex, and absence of H 2O2-producing Lac-
tobacillus species were independently associated with an increased
likelihood of cervicitis among women with BV. Vaginal coloni-
zation with H 2O2-producing Lactobacillus species was associated
with a 60% reduction in the likelihood of cervicitis. Douching,
cervical ectopy, and smoking, which were previously reported to
be associated with cervical inflammation and infection [33, 34],
were not independently associated with cervicitis.
Our findings have several implications, particularly for the
detection of associations distinct from those reported in earli-
er studies [33]. In our study, cervicitis was not associated with
some typical risk factors that indicate recent sexual exposure
to potential genital pathogens, including an increasing number
of partners and frequency of recent vaginal sex. Coupled with
Cervicitis and Bacterial Vaginosis • JID 2006:193 (1 March) • 619
Table 1. Univariate associations between the characteristics of the subjects and the presence of cervicitis.

Subjects Subjects
with cervicitisa without cervicitisa
Characteristic (n p 63) (n p 361) OR (95% CI) P
Age, years .006
14–19 4 (6) 94 (26) 1.0b
20–24 18 (29) 110 (30) 3.8 (1.3–11.8)
25–29 16 (25) 68 (19) 5.5 (1.8–17.3)
⭓30 25 (40) 89 (25) 6.6 (2.2–19.7)
Race .07
European American 21 (33) 90 (25) 1.0b
African American 32 (51) 237 (66) 0.6 (0.3–1.1)
Other 10 (16) 34 (9) 1.3 (0.5–2.9)

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Education, no. of years .09
⭐12 39 (62) 180 (50) 1.6 (0.9–2.8)
⭓13 24 (38) 179 (50) 1.0b
Regular smoker .1
Yes 26 (41) 187 (52) 0.7 (0.4–1.1)
No 37 (59) 174 (48) 1.0b
Time since last douching, days .2
0–7 5 (8) 17 (5) 2.0 (0.7–5.8)
8–30 5 (8) 34 (9) 1.0 (0.4–2.8)
⭓31 or no history of douching 17 (27) 62 (17) 1.9 (1.0–3.6)
Does not currently douche 36 (57) 248 (69) 1.0b
Chlamydia trachomatis test result .5
Positive 4 (6) 16 (4) 1.5 (0.5–4.5)
Negative 59 (94) 345 (96) 1.0b
Neisseria gonorrhoeae test result .5
Positive 4 (6) 14 (4) 1.7 (0.5–5.3)
Negative 59 (94) 347 (96) 1.0b
Oral hormonal contraceptive use during month before enrollment .4
Yes 10 (16) 73 (20) 1.3 (0.7–2.8)
No 53 (84) 288 (80) 1.0b
Depo-Provera, administered during the month before enrollment .05
Yes 2 (3) 44 (12) 0.2 (0.1–1.0)
No 61 (97) 317 (88) 1.0b
Tubal ligation .02
Yes 11 (17) 29 (8) 2.4 (1.1–5.1)
No 52 (83) 332 (92) 1.0b
History of genital herpes .9
Yes 2 (3) 13 (4) 0.9 (0.2–4.0)
No 61 (97) 348 (96) 1.0b
Cervical ectopy .04
Present 5 (8) 69 (19) 0.4 (0.1–0.9)
Absent 58 (92) 291 (81) 1.0b
History of sex with male partners, no. of partners
During lifetime .1
0–1 2 (3) 17 (5) 1.0b
2–5 16 (27) 110 (31) 1.2 (0.3–5.9)
6–10 12 (20) 105 (30) 1.0 (0.2–4.7)
⭓11 30 (50) 119 (34) 2.1 (0.5–9.8)
During the year before enrollment .001
0 5 (8) 12 (3) 1.0b
1 12 (19) 153 (43) 0.2 (0.1–0.6)
2 23 (36) 100 (28) 0.6 (0.2–1.7)
3–9 18 (29) 90 (25) 0.5 (0.2–1.5)
⭓10 5 (8) 4 (1) 3.0 (0.6–16.1)
(continued)
Table 1. (Continued.)

Subjects Subjects
with cervicitisa without cervicitisa
Characteristic (n p 63) (n p 361) OR (95% CI) P
During the 30 days before enrollment .001
0 12 (19) 61 (17) 1.0b
1 35 (56) 266 (74) 0.7 (0.3–1.4)
⭓2 16 (25) 34 (9) 2.4 (1.01–5.6)
New male sex partner during the 30 days before enrollment .001
Yes 20 (32) 51 (14) 2.8 (1.5–5.2)
No 43 (68) 310 (86) 1.0b
Rectal sex during the 30 days before enrollment .7
Yes 4 (6) 28 (8) 0.8 (0.3–2.4)

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No 59 (94) 333 (92) 1.0b
Vaginal sex during the 30 days before enrollment, no. of episodes .2
0 12 (19) 66 (18) 1.0b
1–12 34 (54) 232 (64) 0.8 (0.4–1.6)
⭓13 17 (27) 63 (17) 1.5 (0.7–3.4)
Time since last episode of vaginal sex, no. of days .1
0–7 42 (67) 191 (53) 1.5 (0.7–3.2)
8–30 12 (19) 109 (30) 0.7 (0.3–1.9)
⭓31 or no history of vaginal sex 9 (14) 61 (17) 1.0b
History of sex with female partners, no. of partners
During lifetime .7
0 58 (92) 328 (91) 1.0b
1 0 11 (3) …
⭓2 5 (8) 21 (6) 1.3 (0.5–3.7)
During the year before enrollment .2
0 58 (92) 340 (94) 1.0b
1 1 (2) 12 (3) 0.5 (0.1–3.8)
⭓2 4 (6) 9 (3) 2.6 (0.8–8.7)
During the 30 days before enrollment .04
0 59 (94) 355 (98) 1.0b
⭓1 4 (6) 6 (2) 4.0 (1.1–14.6)
New partner during the 30 days before enrollment .08
Yes 2 (3) 2 (1) 5.9 (0.8–42.6)
No 61 (97) 359 (99) 1.0b
Time since last episode of receptive oral sex, no. of days .002
0–7 33 (52) 107 (30) 2.9 (1.5–5.4)
8–30 12 (19) 93 (26) 1.2 (0.5–2.6)
⭓31 or no history of receptive oral sex 17 (27) 158 (44) 1.0b

NOTE. Data are no. (%) of subjects, unless indicated otherwise. CI, confidence interval; OR, odds ratio.
a
Data were not available for all variables for all subjects.
b
Reference 95% CI.

our finding that increasing age was independently associated
with cervicitis, this suggests a potential role for an intrinsic
local host immune response as a mediator of cervical inflam-
mation. Further analyses will assess the presence of cervicovag-
inal cytokines in these subjects, which may offer some insight
about this hypothesis. We also identified risk factors for cer-
vicitis that are consistent with the epidemiological findings for
BV, including increasing age [8], absence of H 2O2–producing
lactobacilli, [35, 36], and report of sex with a female partner
[37]. These findings suggest that the development of cervicitis
may be promoted by factors associated with persistent or pro-
longed disruption of normal vaginal flora, a concept supported
by observations that levels of proinflammatory vaginal cyto-
kines—such as interleukin (IL)–1b, IL-6, and IL-8—decrease
after successful treatment of BV [38]. We also observed an
association between receptive oral sex and BV, as reported else-
where by other investigators [39, 40]. Finally, exogenous hor-
mone therapy may have directional effects on genital mucosal
inflammation, with estrogen up-regulating and progesterone
down-regulating the local immune response to some pathogens
[41]. Although we observed an inverse association between the
use of DMPA and cervicitis in univariate analysis, this asso-
ciation was not significant in multivariable analysis, likely be-
cause of the small numbers of women involved.

Cervicitis and Bacterial Vaginosis • JID 2006:193 (1 March) • 621

Table 2. Frequency and concentration of vaginal bacteria, by presence or absence of cervicitis.

No. (%) of subjects with vaginal bacteria Concentration of vaginal bacteria, cfu/mL
In subjects In subjects
With cervicitis Without cervicitis with cervicitis without cervicitis
Vaginal microorganism (n p 63) (n p 361) Pa (n p 63) (n p 361) P
b

Gardnerella vaginalis 63 (100) 354 (99) 1.0 108.1 108.3 .2

H2O2-producing lactobacilli 10 (16) 113 (32) .01 102.8 106.1 !.001
Escherichia coli 26 (41) 101 (28) .05 105.1 104.9 .9
Enterococcus species 22 (35) 112 (31) .7 105.1 104.6 .06
Coagulase-negative staphylococci 36 (57) 208 (58) .9 103.7 103.5 .5
Group B streptococci 12 (19) 74 (21) .9 105.1 105.1 .6
Viridans streptococci 34 (54) 197 (55) .9 105.2 105.1 .9
Diphtheroids 51 (81) 277 (78) .7 104.1 103.9 .09
Yeast 3 (5) 27 (8) .6 103.5 104.1 .4

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Mycoplasma hominis 46 (73) 262 (74) 1.0 106.3 106.1 .1
Ureaplasma urealyticum 52 (83) 297 (83) .9 105.3 105.1 .6
Bacteroides fragilis group 3 (5) 21 (6) 1.0 103.1 103.3 .3
Bacteroides ureolyticus 9 (14) 69 (19) .4 104.1 104.3 .8
Prevotella bivia 37 (59) 212 (60) .9 107.3 107.1 .04
Nonpigmented Prevotella species 48 (76) 287 (81) .4 107.2 107.1 .98
Black-pigmented anaerobic GNR 58 (92) 296 (83) .09 106.4 106.5 .8
Black-pigmented Prevotella species 31 (49) 166 (47) .8 106.7 106.6 .99
Porphyromonas species 45 (71) 238 (67) .6 106.1 105.7 .9
Mobiluncus species 11 (17) 64 (18) 1.0 106.1 105.6 .1
Anaerobic GPR 18 (29) 122 (34) .5 106.1 106.8 .2
Anaerobic GPC 53 (84) 312 (88) .4 106.3 106.1 .5

NOTE. GNR, gram-negative rod; GPC, gram-positive cocci; GPR, gram-positive rod.
a
x2 test.
b
Mann-Whitney U test, for colonized women.

Elucidation of the associations between cervicitis, vaginal
H 2O2-producing Lactobacillus species, and the anaerobic bac-
teria associated with BV will require prospective studies. How-
ever, existing data support several possible mechanisms. First,
H 2O2 itself has broad antimicrobial activity [42], and the pres-
ence of vaginal H 2O2-producing lactobacilli is strongly asso-
ciated with decreased prevalence and acquisition of gonorrhea
and HIV infection [10, 35] and with sustained long-term col-
onization with these lactobacilli [36]. Lactobacilli that pro-
duce H 2O2 may exert a direct effect not only against pathogens
known to cause MPC but also against anaerobes associated with
BV itself. The potential pathogenicity of these anaerobes—for
example, some augment expression of HIV in T cells in vitro
[43] and may potentiate HIV-1 RNA expression in the genital
tract of HIV-infected women [24]—may be enhanced in the
absence of Lactobacillus species. Second, vaginal mucins are
depleted in BV, along with their protective physical and im-
munologic components. This may expose vulnerable mucosa
to the effects of glycosidases and proteinases produced by BV-
associated flora [44, 45]. If this process occurs at the cervix,

Table 3. Risk factors for cervicitis, adjusted for the presence of Chlamydia trachomatis
and Neisseria gonorrhoeae and other characteristics.

Characteristic OR (95% CI) P

Age, years
a
14–19 1.0
20–24 6.7 (2.0–22.4) .002
25–29 9.7 (2.7–35.1) .001
⭓30 12.1 (3.6–40.2) !.001
Education, ⭐12 years 2.4 (1.3–4.6) .006
Sexual history during the 30 days before enrollment
New male sex partner 2.7 (1.4–5.4) .004
Female sex partner 6.2 (1.3–28.3) .02
Receptive oral sex during the 7 days before enrollment 2.3 (1.2–4.2) .008
Cervical infection with C. trachomatis or N. gonorrhoeae 2.8 (1.0–7.7) .051
Absence of vaginal H2O2-producing lactobacilli 2.7 (1.3–5.9) .01

NOTE. CI, confidence interval; OR, odds ratio.

a
Reference 95% CI.

622 • JID 2006:193 (1 March) • Marrazzo et al.

where endocervical mucous evidences intrinsic antimicrobial
activity [46, 47], cervicitis may conceivably result. Finally, com-
plete absence of H 2O2-producing lactobacilli (and high quan-
tities of the most proinflammatory gram-negative bacteria) may
be associated with extreme disruption of vaginal cytokine reg-
ulation. These cytokines include secretory leukocyte protease
inhibitor, which helps to maintain a healthy vaginal epithelium
[48]; IL-10, which may increase the susceptibility of macro-
phages to HIV-1 infection [49]; and IL-1b, which has been
associated with a higher number of vaginal neutrophils among
women with BV [50].
The scant data available suggest that antibiotics for the treat-
ment of C. trachomatis and N. gonorrhoeae infection do not
adequately treat nonchlamydial, nongonococcal cervicitis. The
combination of doxycycline and amoxicillin was initially ef-
fective in the treatment of cervicitis among clients of a sexually
transmitted diseases clinic, but, at 3 months after treatment, it
was associated with high rates (30%) of persistent (23%) or
recurrent (33%) cervicitis, in the absence of detectable infec-
tion with C. trachomatis, N. gonorrhoeae, genital mycoplasma,
or Gardnerella vaginalis [51]. In another study, treatment with
ofloxacin effected similar improvement of cervicitis, regardless
of whether C. trachomatis was detected [52]. Finally, of 51
women with cervicitis and BV who were randomized to receive
doxycycline and ofloxacin and either intravaginal metronida-
zole or placebo, those who received metronidazole had a higher
rate of resolution of cervicitis at 2 and 4 weeks after treatment,
and women whose BV resolved were more likely to have res-
olution of cervicitis at 2 weeks after treatment, regardless of
the regimen that they received [21].
The present study has some limitations. First, Mycoplasma
genitalium has recently been implicated as a sexually trans-
missible cause of cervicitis [53]; we did not look for this or-
ganism. Second, although our subjects had no clinical evidence
of genital herpes, and although a self-reported history of genital
herpes was not associated with cervicitis, herpes simplex virus
can cause cervical inflammation in the absence of visible lesions.
We did not perform diagnostic tests for this infection. Because
the presence of BV may increase the risk of acquiring genital
herpes simplex virus type 2 infection [54], this association re-
quires further study.
In summary, our findings support an independent role for
BV in the pathogenesis of cervicitis, and they extend our current
understanding of the critical role of H 2O2-producing Lacto-
bacillus species in the maintenance of a healthy cervicovagi-
nal environment. Because cervicitis occurring in the absence
of detectable gonococcal or chlamydial infection may confer
an increased risk of a poor outcome of pregnancy [55] and
may predict upper genital tract disease [56], definition of eti-
ologies and effective treatment should be a priority. Future
research should focus on clarifying the immune response of
the cervix to disruptions in the normal vaginal flora, as well
as ways to initiate and sustain vaginal colonization with H 2O2-
producing lactobacilli.
Acknowledgments
We thank the clinic staff responsible for the conduct of the present study,
as well as the women enrolled in the study.
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