ajog.

org

Editorials

Treatment of cervical dysplasia and the risk of

preterm birth: understanding the association
Heather A. Frey, MD, MSCI; Shayna N. Conner, MD, MSCI

ver the past decade, there has been an evolution in the

screening and management of cervical dysplasia toward
a more conservative approach. Accumulating data from large
studies demonstrating a low risk of cervical cancer among
adolescents and women 21-24 years of age supported these
changes.1,2 However, a major stimulus for the new guidelines
was concern regarding the potential adverse effects of excisional procedures on subsequent pregnancy outcomes,
namely, preterm birth.3,4 The published evidence overall reects an increased risk of preterm birth in women with a
history of a cervical excisional procedure.5,6 However, recent
studies have found a similar increased risk for preterm birth in
women with cervical dysplasia without a history of cervical
excision.7-11 This suggests that perhaps cervical excisional
procedures do not cause subsequent preterm birth, but rather
the risk factors for cervical dysplasia are similar to those for
preterm birth. As a result of these recent ndings, there has
been a renewed interest in clarifying the relationship among
cervical dysplasia, excisional procedures, and preterm delivery.
Published in this issue of the journal, the study by Miller
et al12 aims to further investigate whether cervical dysplasia
without a cervical excisional procedure is associated with an
increased risk of preterm birth, and to determine if the
possible increased risk can be attributed to the presence of a
short cervix. Miller et al12 conducted a retrospective cohort
study including 18,528 pregnant women who underwent
routine cervical length screening over the 4-year study period.
These women were stratied into 3 groups based on review of
medical records: no prior dysplasia, history of dysplasia
without cervical excisional procedure, and prior excisional
procedure. Using multivariable logistic regression equations,
they found that after adjusting for the presence of a short
cervix and other potential confounders, a prior excisional
procedure (adjusted odds ratio [aOR], 1.31; 95% condence
interval [CI], 1.04e1.64), but not prior dysplasia alone (aOR,
1.02; 95% CI, 0.85e1.21) was associated with preterm birth.

From the Departments of Obstetrics and Gynecology at Ohio State

University School of Medicine, Columbus, OH (Dr Frey) and Washington
University in St Louis, St Louis, MO (Dr Conner).
Received July 6, 2015; accepted Aug. 5, 2015.
The authors report no conict of interest.
Corresponding author: Heather A. Frey, MD, MSCI. Heather.Frey@
osumc.edu
0002-9378/free
2015 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.ajog.2015.08.012

See related article, page 543

One of the key strengths of this study was the incorporation of cervical length data in the analysis. This is
fundamental to understanding possible mechanisms by which
cervical excisional procedures increase the risk of preterm
delivery. The authors report that women with a prior cervical
excisional procedure had the highest incidence of short cervix
(2.2%) within the cohort. Despite this, prior excisional procedure was independently associated with an increased risk of
preterm birth regardless of cervical length. The implication is
that the increased risk of preterm birth following a cervical
excisional procedure is not solely the result of the loss of
cervical tissue leading to a short cervix. This is further supported by the nding that an interaction term for short cervical length and prior excisional procedure in relation to
preterm birth was not signicant.
Ideally, the question of whether or not a cervical excisional
procedure actually causes subsequent preterm birth would be
best answered in a randomized controlled trial. However, this
is not possible for obvious ethical reasons, thus we rely on
large, well-conducted observational studies like this study
performed by Miller et al12 to guide clinical care. However,
there are some limitations to this study that should be
considered. First, dysplasia history and history of an excisional procedure were determined by patient report on the
prenatal record, thereby increasing the likelihood of recall
bias and misclassication bias. Women are more likely to
recall and report cervical excisional procedures than untreated dysplasia, which could have biased the results away
from the null. In addition, the authors do not report the
amount of missing data with regards to dysplasia history. It is
important to note that the primary outcome in this study was
preterm birth <37 weeks, which includes both spontaneous
and indicated preterm births, and may not accurately reect
the mechanism of preterm birth as a result of cervical excision. Despite including all preterm births, the overall preterm
birth rate in this study (6.6%) is low, making the results less
generalizable to high-risk populations. Finally, as the authors
discuss, there is the potential for residual confounding, which
may account for their results. In this study, they did not
control for severity of dysplasia, depth of cervical excision, or
socioeconomic factors. Due to these limitations, especially in
a study where the CI of the positive nding so closely approaches 1, the results should be interpreted with caution.
When a new study is published, it is wrong to immediately
incorporate the results into clinical care, and disregard prior
studies on the subject. We must instead integrate these new
ndings with previous literature. Ideally, this assessment can
be aided by patient levelebased quality metaanalyses.
To properly assess the effect of cervical dysplasia on the
incidence of preterm birth, women with cervical dysplasia but
OCTOBER 2015 American Journal of Obstetrics & Gynecology

445

ajog.org

Editorials
no excisional procedures should be compared to similar
women with neither cervical dysplasia nor prior excisional
procedures. No metaanalysis of such studies exists, and data
are very limited. One study including 75 women with precancerous lesions and no treatment found no increased risk
of preterm birth.13 Another study reported instead increased
risk of premature delivery in women with untreated cervical
dysplasia.14
To better delineate the effect of excisional procedures in
women with precancerous changes of the cervix, the most
appropriate control group is women with similar precancerous changes of the cervix, but no excisional procedure. One
metaanalysis of such studies shows a signicant 27%
increased incidence of preterm birth associated with excisional treatment, after adjusting for confounders.10 In
contrast, a metaanalysis limited to only loop electrosurgical
excision procedures showed no increased risk of preterm
birth when women with prior loop electrosurgical excision
procedure were compared to women with history of cervical
dysplasia but no cervical excision.11 Despite the major
contribution to assessing the association between precancerous cervical lesions (dysplasia alone) and preterm birth made
by Miller et al12 in this edition of our journal, clearly more
data are needed to make a nal conclusion.
Although the study from Miller et al12 shows an independent association between history of cervical excisional
procedure and the risk of preterm delivery, the magnitude of
the risk should be acknowledged when considering the clinical implications of this nding. In this study, a history of
cervical excision was associated with only a 30% increased
risk (aOR, 1.3) of preterm delivery, consistent with the
metaanalysis data.12 In contrast, use of in vitro fertilization to
conceive was associated with a 130% increased risk (aOR, 2.3)
of prematurity in the study. Furthermore, the risk of delivering prematurely was >5 times higher if a woman had a
cervical length of
2.5 cm, regardless of her history of cervical excisional procedure. In light of this, it seems reasonable
to counsel women about a potential increased risk of preterm
delivery if they have had a prior cervical excisional procedure.
However, without data from studies that specically evaluate
potential interventions to prevent prematurity in women with
a prior excisional procedure, these women should receive
routine prenatal care, which may include cervical length
measurement as part of universal cervical length screening.
Cerclage placement in the absence of other indications is not
currently supported by the literature.
Clearly there is a relationship between prior cervical excisional procedure and preterm birth, however the nature and

446 American Journal of Obstetrics & Gynecology OCTOBER 2015

etiology of this association remains undened. The study by

Miller et al12 shows that cervical shortening may not be the
only specic process that leads to an increased risk for preterm birth in these women. Further research is needed
focusing on clarifying the biological mechanism by which
prior cervical excisional procedure increases the risk of preterm delivery. Until this relationship is further delineated,
given the conicting data, the current less interventional
approach to the management of cervical dysplasia among
young women seems prudent.
REFERENCES
1. Moore G, Fetterman B, Cox JT, et al. Lessons from practice: risk of CIN3
or cancer associated with an LSIL or HPV-positive ASC-US screening
result in women age 21-24. J Low Genit Tract Dis 2010;14:97-102.
2. Katki HA, Schiffman M, Castle PE, et al. Estimating 5-year risk of
CIN3 to guide the management of women aged 21-24. J Low Genit
Tract Dis 2013;17:S64-8.
3. ACOG. Management of abnormal cervical cancer screening test results and cervical cancer precursors. Practice bulletin no. 140. Obstet
Gynecol 2013;122:1338-66.
4. Massad LS, Einstein MH, Huh WK, et al. 2012 Updated consensus
guidelines for the management of abnormal cervical cancer screening
tests and cancer precursors. Obstet Gynecol 2013;121:829-46.
5. Poon LCY, Savvas M, Zamblera D, Skyfta E, Nicolaides KH. Large
loop excision of transformation zone and cervical length in the prediction
of spontaneous preterm delivery. Br J Obstet Gynaecol 2012;119:
692-8.
6. Samson SA, Bentley JR, Fahey TH, McKay DJ, Gill GH. The effect of
loop electrosurgical excision procedure on future pregnancy outcome.
Obstet Gynecol 2005;105:325-32.
7. Himes KP, Simhan HN. Time from cervical conization to pregnancy
and PTB. Obstet Gynecol 2007;109:314-9.
8. Werner CL, Lo JY, Heffernan T, Grifth WF, McIntire DD, Leveno KJ.
Loop electrosurgical excision procedure and risk of PTB. Obstet Gynecol
2010;115:605-8.
9. Andia D, Mozo de Rosales F, Villasante A, Rivero B, Diez J, Perez C.
Pregnancy outcome in patients treated with cervical conization for cervical intraepithelial neoplasia. Int J Gynecol Obstet 2011;112:225-8.
10. Bruinsma FJ, Quinn MA. The risk of PTB following treatment for
precancerous changes in the cervix: a systematic review and metaanalysis. BJOG 2011;118:1031-41.
11. Conner SN, Frey HA, Cahill AG, Macones GA, Colditz GA, Tuuli MG.
Loop electrosurgical excision procedure and risk of preterm birth: a
systematic review and meta-analysis. Obstet Gynecol 2014;123:752-61.
12. Miller ES, Sakowicz A, Grobman WA. The association between
cervical dysplasia, a short cervix, and preterm birth. Am J Obstet Gynecol
2015;213:543.e1-4.
13. Watson LF, Rayner J-A, King J, Jolley D, Forster D. Intracervical
procedures and the risk of subsequent very preterm birth: a case-control
study. Acta Obstet Gynecol Scand 2012;91:204-10.
14. Bruinsma F, Lumley J, Tan J, Quinn M. Precancerous changes in
the cervix and the risk of subsequent preterm birth. BJOG 2007;114:
70-80.