Cervical Cancer Management

Cervical intraepithelial neoplasia: Management of low-grade and high-grade lesions - UpToDate 3/27/19, 17)19
Official reprint from UpToDate®

www.uptodate.com ©2019 UpToDate, Inc. and/or its affiliates. All Rights Reserved.
Cervical intraepithelial neoplasia: Management of low-grade and high-grade lesions
Author: Jason D Wright, MD

Section Editor: Barbara Goff, MD
Deputy Editor: Sandy J Falk, MD, FACOG
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2019. | This topic last updated: Apr 30, 2018.
INTRODUCTION — Cervical intraepithelial neoplasia (CIN) is a premalignant condition of the uterine cervix [1]. The ectocervix
(surface of the cervix that is visualized on vaginal speculum examination) is covered in squamous epithelium, and the
endocervix, including the cervical canal, is covered with glandular epithelium. CIN refers to squamous abnormalities. Glandular
cervical neoplasia includes adenocarcinoma in situ and adenocarcinoma. (See "Cervical cytology: Evaluation of atypical and
malignant glandular cells" and "Cervical adenocarcinoma in situ" and "Invasive cervical adenocarcinoma".)
Screening tests for cervical cancer include cervical cytology and testing for oncogenic subtypes of human papillomavirus (HPV)
(table 1). Follow-up of abnormalities in screening tests with colposcopy and cervical biopsy may result in a diagnosis of CIN,
glandular neoplasia, or cervical cancer [2].
CIN may be low grade or high grade. Women with low-grade CIN have a low potential for developing cervical malignancy, while
those with high-grade lesions are at high risk of progression to malignancy. In managing women with CIN, the goal is to prevent
possible progression to invasive cancer while avoiding overtreatment of lesions that are likely to regress.
Management of CIN is reviewed here. Related issues are discussed separately:
● Treatment of CIN (see "Cervical intraepithelial neoplasia: Treatment and follow-up")
● Cervical cancer screening (see "Screening for cervical cancer")
● Evaluation of abnormal screening tests and diagnosis of CIN (see "Cervical cytology: Evaluation of atypical squamous cells
(ASC-US and ASC-H)" and "Cervical cytology: Evaluation of low-grade squamous intraepithelial lesions (LSIL)" and
"Cervical cytology: Evaluation of high-grade squamous intraepithelial lesions (HSIL)")
● Techniques for CIN treatment (see "Cervical intraepithelial neoplasia: Procedures for cervical conization" and "Cervical
intraepithelial neoplasia: Ablative therapies")
● Reproductive effects of CIN treatment (see "Cervical intraepithelial neoplasia: Reproductive effects of treatment")
● Diagnosis of cervical cancer (see "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and
diagnosis")
TERMINOLOGY — In 2012, the Lower Anogenital Squamous Terminology (LAST) project of the College of American Pathology
and American Society for Colposcopy and Cervical Pathology published changes in the terminology used to describe human
papillomavirus (HPV)-associated squamous lesions of the anogenital tract [3,4]. In the LAST system, histologic cervical findings
are described using the same terminology as cytologic findings, as follows (figure 1):
● CIN 1 in the previous terminology system is referred to as low-grade squamous intraepithelial lesion (LSIL).
● CIN 2 is stratified according to p16 immunostaining to identify precancerous lesions. CIN 2 has poor reproducibility and is
likely a heterogeneous mix that includes lesions that could be classified as CIN 1 or 3. Specimens that are p16-negative are
referred to as LSIL and those that are p16-positive are referred to as high-grade squamous intraepithelial lesions (HSIL).
● CIN 3 is referred to as HSIL.
https://www.uptodate.com/contents/cervical-intraepithelial-neoplas…earch_result&selectedTitle=1~150&usage_type=default&display_rank=1 Page 1 of 20
CIN terminology is commonly used in clinical and practice, and in this topic, the CIN terminology will be used because that
terminology is used in the American Society of Colposcopy and Cervical Pathology guidelines [2].
Terminology for CIN is discussed in detail separately. (See "Cervical intraepithelial neoplasia: Terminology, incidence,
pathogenesis, and prevention", section on 'Terminology'.)
OVERVIEW OF MANAGEMENT — There are two management approaches to CIN: continued observation (with cervical
cytology, human papillomavirus [HPV] testing, and colposcopy) and treatment with an excision or ablation of the cervical
transformation zone (an anatomic area that contains the transition from the squamous epithelium of the ectocervix to the
glandular epithelium of the endocervix), or less commonly, hysterectomy.
In some clinical contexts, "see-and-treat" protocols are used, in which evaluation and management are performed at the same
visit.
Observation versus treatment — Decisions regarding management of CIN depend upon the risk of cervical cancer, risks
associated with treatment, and the likelihood of compliance with a management plan.
Observation is used for lesions that are highly likely to regress (CIN 1). CIN 2,3 lesions are associated with a high risk of
developing cervical cancer, and these are typically treated with cervical excision or ablation. However, there is some chance that
these lesions will regress, and observation is used in some patients. This is particularly the case for women who plan future
childbearing, since excisional procedures may result in future adverse obstetric outcomes. (See "Cervical intraepithelial
neoplasia: Treatment and follow-up", section on 'Future obstetric risks' and "Cervical intraepithelial neoplasia: Reproductive
effects of treatment".)
Treatment is generally performed only based upon histologic results from colposcopically-directed biopsy. In some cases,
colposcopy is not adequate and/or there are recurrent high-grade cytologic findings (atypical squamous cells, cannot rule out
high-grade squamous intraepithelial lesion [ASC-H] or high-grade squamous intraepithelial lesion [HSIL]); an excisional
procedure is performed for the purpose of diagnosis, but this is the same procedure used for treatment, and further treatment
may not be required. In addition, treatment in "see-and-treat" protocols is provided based upon colposcopic appearance of a
lesion without confirmation from biopsy result.
The evaluation approach presented here is provided by the 2012 consensus guidelines of the American Society for Colposcopy
and Cervical Pathology in collaboration with multiple professional societies and government organizations in the United States
and Canada, including the American College of Obstetricians and Gynecologists, the Society of Obstetricians and
Gynaecologists of Canada, the Society of Gynecologic Oncology, the American Cancer Society, Centers for Disease Control and
Prevention, and the US Food and Drug Administration. The algorithms for the consensus guidelines can be found online.
See-and-treat protocols — Immediate treatment based upon a "see-and-treat" or "screen-and-treat" protocol is used for women
who are unlikely to be able to comply with a management plan (either observation or treatment at a later date after histologic
results are available) and is acceptable for women with HSIL cytology.
"See-and-treat" protocols consist of evaluation and treatment in one visit, with an excisional procedure performed if there is a
lesion with a high-grade colposcopic appearance. This approach is discussed in detail separately. (See "Screening for cervical
cancer in resource-limited settings", section on 'Screen and treat protocols'.)
LOW-GRADE LESIONS: CIN 1 — CIN 1 is a low-grade lesion caused by human papillomavirus (HPV) subtypes of both low and
high oncogenic risk (table 1). The management of women with CIN 1 depends upon the preceding cytology. When CIN 1 is
preceded by low-grade cytologic findings (atypical squamous cells of undetermined significance [ASC-US] or low-grade
squamous intraepithelial lesions [LSIL]), observation is advised rather than treatment, unless CIN 1 persists for two or more
years.
The risk of high-grade preinvasive disease or cancer is higher in women with CIN 1 preceded by a cytologic finding of atypical
squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) or high-grade squamous intraepithelial
lesion (HSIL). These women may be managed either with observation or immediate treatment.
Risk of malignant disease — CIN 1 lesions will regress in most women. As an example, a retrospective study of 680 women
with biopsy-proven CIN 1 found the following cytology and/or histology results: (1) at six months, 49 percent regressed to
negative, 35 percent had persistent CIN 1, and 7 percent had high-grade lesions; (2) at 12 months, among the patients with
negative results at six months: 80 percent were negative, 17 percent had low-grade lesions, and 4 percent had high-grade
https://www.uptodate.com/contents/cervical-intraepithelial-neoplas…arch_result&selectedTitle=1~150&usage_type=default&display_rank=1 Page 2 of 20
lesions; and (3) at 12 months, among patients with persistent CIN 1 at six months: 50 percent were negative, 46 percent had low-
grade lesions, and 4 percent had high-grade lesions [5].
The outcome of CIN 1 lesions depends upon the preceding cytology:
● CIN 1 preceded by ASC-US or LSIL cytology – Studies have reported that 4 to 13 percent of women with CIN 1 preceded by
low-grade cytology will be diagnosed with CIN 2,3 within 6 to 24 months of follow-up [6-9]. No studies have reported invasive
cervical cancer in this patient population within this follow-up period.
● CIN 1 preceded by ASC-H or HSIL cytology – In one study, women with CIN 1 preceded by HSIL had a five-year risk of CIN
3+ of 15 percent [9].
CIN 1 preceded by lesser abnormalities — The 2012 American Society for Colposcopy and Cervical Pathology guidelines use
the term "lesser abnormalities" to refer to: ASC-US cytology, LSIL cytology, HPV 16 or 18 infection (detected with HPV
genotyping), or persistent HPV infection [2].
Women ages 25 or older — Women ages 25 years or older with CIN 1 (or no lesion) preceded by lesser abnormalities are
managed as follows (algorithm 1) (these recommendations are the same as for a finding of no lesion at colposcopy) [2,10]:
● HPV/cytology cotesting should be performed in 12 months.
• If the results of cotesting are both normal cytology and HPV negative, age-appropriate cervical cancer screening tests
should be repeated in three years (table 2). If the results are again normal cytology and HPV negative (if HPV testing
was performed), the patient may resume routine screening.
• If cotesting results are either abnormal cytology (ASC-US or a more severe abnormality) or HPV positive, colposcopy
should be performed.
If no lesion is found, the patient should be followed using this algorithm (algorithm 1).
If CIN 1 is found and persists for at least two years, the patient should be either followed using this algorithm (algorithm
1) or treated with cervical ablation or a diagnostic excisional procedure. Excision is preferred in the following
circumstances: inadequate colposcopy, positive endocervical sampling, or previous treatment for CIN.
If CIN 2,3 is found, the results should be managed as appropriate. (See 'High-grade lesions: CIN 2,3' below.)
The safety of observation rather than immediate treatment of CIN 1 was illustrated in a randomized trial (n = 415) of women with
low-grade cytology [8]. The trial found no significant difference in the rate of CIN 2,3 at 18 months following immediate treatment
with loop electrosurgical excision procedure (LEEP) compared with observation every six months with cytology, HPV testing, and
colposcopy.
Observation using HPV/cytology cotesting appears to be superior to follow-up with cytology or HPV testing alone. This is based
upon observational data from the records of a large health maintenance organization, including 20,319 women who underwent
colposcopy and had a result of no lesion or CIN 1 [9]. In women for whom the antecedent screening tests were ASC-US, HPV
positive, or LSIL, the five-year risk of CIN 2+ was significantly lower in women who had a single negative cotest (1.1 percent)
than those with two sequential negative cytology results (4.0 percent), and was comparable to women with two sequential
negative HPV tests (1.8 percent).
By contrast, some data support use of HPV testing alone rather than HPV/cytology cotesting. Data from the ASC-US/LSIL Triage
Study (ALTS) randomized trial included follow-up results for 1539 women with low-grade screening results (ASC-US cytology,
HPV-positive, or LSIL cytology) who underwent colposcopy and had no lesion or CIN 1 [11]. The sensitivity for detection of CIN
2,3 was similar for HPV/cytology cotesting compared with HPV testing alone at 12 months (92 versus 95 percent). A
disadvantage of the cotesting approach was that more women were referred to colposcopy (64 versus 55 percent).
Women ages 21 to 24 — The recommendations for management of CIN differ for women ages 21 to 24 years from those for
women 25 and older. This is because the risk of cervical cancer is low in this patient population. From 1999 to 2008 in the United
States, the annual incidence of cervical cancer among women ages 20 to 24 was 1.4 per 100,000 women compared with women
ages 25 to 39, for whom the incidence was 5.9 to 14.2 per 100,000 [12]. In addition, the rate of HPV infection is high in this
patient population and cervical intraepithelial lesions often regress spontaneously [13,14]. In a cohort study of 2065 women 18 to
29 years of age, 61 percent of women with a newly diagnosed high-risk HPV infection cleared the infection at 12 months of
follow-up [15].
Women ages 21 to 24 with CIN 1 (or no lesion) preceded by ASC-US or LSIL are managed as follows (algorithm 2) [2,10]:
● Cytology should be repeated in 12 months.
• If the result is negative, ASC-US, or LSIL, cytology should again be repeated in 12 months. If cytology is again negative,
the patient may resume routine screening. If a cytologic abnormality is found at the 24-month follow-up, colposcopy
should be performed.
• If the results of repeat cytology are ASC-H or HSIL at the 12-month follow-up, colposcopy should be performed.
CIN 1 preceded by ASC-H or HSIL — In addition to ASC-H and HSIL, CIN 1 preceded by atypical glandular cells is also
associated with an increased risk of subsequent high-grade disease.
Management of atypical glandular cells is discussed separately. (See "Cervical cytology: Evaluation of atypical and malignant
glandular cells", section on 'Negative or low-grade findings on initial evaluation'.)
Women ages 25 and older — Women ages 25 years or older with CIN 1 (or no lesion) preceded by ASC-H or HSIL are
managed as follows (algorithm 3) [2,10]:
● Patients may be managed in one of three ways:
• HPV/cytology cotesting at 12 and 24 months – If cotesting is negative at both visits, age-appropriate cervical cancer
screening tests should be repeated in three years (table 2). If cotesting results are HPV positive or any cytologic
abnormality is present (except HSIL), colposcopy should be performed. If cytology shows HSIL, a diagnostic excisional
procedure should be performed.
• Alternatively, a diagnostic excisional procedure may be performed without further testing.
• Alternatively, a review of cytologic, histologic, and colposcopic findings – Results should be managed as appropriate.
When cervical cytology with ASC-H or HSIL is followed by a histologic diagnosis of CIN 1, there is a concern that an underlying
high-grade lesion has been missed by colposcopy and biopsy. For that reason, an excisional diagnostic procedure has
traditionally been recommended. Based upon the obstetric risks associated with excisional procedures, in current practice,
observation is considered a reasonable alternative. The choice of an excisional procedure or observation should take into
account the patient’s preferences, ability to comply with follow-up, and future childbearing plans (excisional procedures may
impact future pregnancies). (See "Cervical intraepithelial neoplasia: Reproductive effects of treatment" and "Cervical
intraepithelial neoplasia: Treatment and follow-up", section on 'Future obstetric risks'.)
In our practice, we counsel patients about the options of HPV/cytology cotesting and a diagnostic excisional procedure. We
suggest HPV/cytology cotesting for patients who desire future childbearing and are willing and able to comply with long-term
follow-up. For other patients, we suggest a diagnostic excisional procedure.
We use review of previous testing only if the findings seem inconsistent (eg, a single test result of ASC-H or HSIL in a patient
with a consistent history of negative or low-grade findings) or for patients that had specimens evaluated at a laboratory with
which we are unfamiliar.
Regarding the type of testing used for observation, follow-up of CIN 1 or no lesion preceded by ASC-H or HSIL with
HPV/cytology cotesting appears to be superior to follow-up with cytology or HPV testing alone. This is based upon data from a
study of 20,319 women who underwent colposcopy and had a result of no lesion or CIN 1 [9]. In women for whom the antecedent
cervical cytology was HSIL or ASC-H, the five-year risk of CIN 2+ was significantly lower in women who had a single negative
cotest (2.2 percent) than those with one negative cytology result (7.0 percent) or one negative HPV test (4.4 percent).
Women ages 21 to 24 — Women ages 21 to 24 years with CIN 1 preceded by ASC-H or HSIL are managed as follows
(algorithm 2 and algorithm 4) [2,10]:
● Observation with cytology and colposcopy every six months for up to two years. The results should be managed as follows:
• Two consecutive negative cytology results and no high-grade colposcopic abnormality (this refers to colposcopic
appearance with an endocervical curettage without confirmation with a biopsy) – The patient may resume routine
screening.
• HSIL on cytology or high-grade colposcopic lesion that persists for one year – A colposcopically directed biopsy should
be performed. If CIN 2,3 is present, the patient should be managed as appropriate. If there is no CIN 2,3, observation
with cytology and colposcopy should continue.
• HSIL on cytology that persists for 24 months in the absence of a histologic finding of CIN 2,3 – A diagnostic excisional
In these algorithms, the terms "high-grade colposcopic abnormality" and "high-grade colposcopic lesion" refer to the visual
appearance of a lesion at colposcopy that has not been confirmed by a biopsy.
Some experts prefer to perform colposcopically directed biopsies if a lesion is found during colposcopy rather than manage a
patient based upon visual appearance. Studies have found the colposcopic impression of whether a lesion is low grade or high
grade has high interobserver variability and low correlation with histology [11,16-18]. As an example, in the ASC-US/LSIL Triage
Study (ALTS), the Reid colposcopic index was used to report the results of 3549 colposcopic examinations, and reviewers
assessed images for each examination [16]. The interobserver correlation was poor (weighted Kappa = 0.17), and the sensitivity
and specificity of a Reid index score of >3/6 to detect CIN 3+ was low to moderate (sensitivity: 37 percent, specificity: 90
percent). However, young women are at a substantial risk for overtreatment, and overuse of biopsy may contribute to this issue.
HIGH-GRADE LESIONS: CIN 2,3 — CIN 2 and 3 are managed in the same way because histologic distinction between the two
grades of CIN is poorly reproducible [19-21]. Given the overall high risk of progression of both CIN 2 and 3, prompt treatment is
recommended. The exceptions to this are pregnant women, who should undergo an excisional procedure only if invasive disease
is suspected, and young women who plan future childbearing, who should be counseled about the risks and benefits of treatment
versus observation. (See 'Pregnant women' below and 'Young women' below.)
Risk of malignant disease — Treatment has been recommended for most patients with CIN 2,3; thus, data are limited on the
natural history of untreated high-grade disease.
For CIN 2 lesions, it appears that approximately half of lesions will regress if left untreated. The natural history of CIN 2 was best
demonstrated in a meta-analysis of 36 studies (both randomized trials and observational studies) including 3160 women with CIN
2 [22]. At 24 months, lesions regressed in 50 percent of women, persisted in 32 percent, and progressed to CIN 3+ in 18 percent.
In a subgroup analysis of 1069 women younger than 30 years, lesions regressed in 60 percent of women, persisted in 23
percent, and progressed in 11 percent. The rate of progression increased with time, from 5 percent at 3 months to 24 percent at
36 months; this result is expected as most women regress, and those remaining are likely at a higher risk of progression.
Progression rates were lower in women with negative human papillomavirus (HPV) testing at baseline; however, this was based
on few data since HPV status was not reported in most studies, and most women regressed at 24 months regardless of initial
HPV status. There were 15 cases of adenocarcinoma in situ and 15 cases of invasive cervical cancer (two of these were
advanced-stage disease). Risk of loss to follow-up is important in deciding whether to treat or manage expectantly. In prospective
studies, the rate of noncompliance with follow-up of 6 to 24 months was approximately 10 percent.
In data from the atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesions (ASC-US/LSIL)
Triage Study (ALTS) randomized trial, regression of CIN 2 was less likely in women with HPV 16 subtype than other subtypes
[23]. One explanation for the lower rate of progression of CIN 2 compared with CIN 3 is that CIN 2 is more likely to be caused by
oncogenic HPV subtypes 31, 33, 35, 39, 45, 51, 52, and 58, which have a weaker association with development of cancer than
the more highly oncogenic subtypes HPV 16 and 18, which are commonly found with CIN 3 [24].
For CIN 3, the estimated spontaneous regression rate is 32 to 47 percent, with 12 to 40 percent progressing to invasive cancer if
untreated [25-30]. The best data on the natural history of histologically confirmed CIN 3 are from an historic study that evaluated
the incidence of invasive cancer over time in two groups of women with CIN 3 (not all women with CIN 3 received treatment): 143
women received close follow-up but no treatment, and 593 women received adequate or probably adequate treatment [30]. The
cumulative incidence of invasive cancer of the cervix/vaginal vault was significantly higher in untreated women at 10 years (20
versus 0.3 percent) and 30 years (31 versus 0.7 percent). Ninety-two of the 143 women who were managed with close follow-up
but no treatment had cytologic evidence of persistent disease 6 to 24 months after the initial diagnosis of CIN 3. In this subgroup,
the cumulative incidence of invasive cancer of the cervix/vaginal vault at 10 and 30 years was 31 and 50 percent, respectively.
Given the high rate of progression to invasive cancer, prolonged follow-up of persistent CIN is no longer recommended.
Management — Women with CIN 2,3, with the exception of young women and pregnant women (see 'Young women' below and
'Pregnant women' below), are managed as follows (algorithm 5) [2,10]:
● Adequate colposcopy (entire squamocolumnar junction is visible circumferentially around the external cervical os) – Either
excision or ablation of the cervical transformation zone may be performed.
● Inadequate colposcopy or recurrent CIN 2,3 or endocervical sampling with CIN 2,3 or ungraded CIN – An excisional
The importance of an excisional procedure for women with an inadequate colposcopy was illustrated in studies that found that as
many as 7 percent of women with CIN 2,3 and an inadequate colposcopic examination had occult invasive cervical cancer
[31,32].
Young women — This patient population is defined in the American Society for Colposcopy and Cervical Pathology guidelines
as follows: "The term 'young women' indicates those who after counseling by their clinicians, consider risk to future pregnancies
from treating cervical abnormalities to outweigh risk for cancer during observation of those abnormalities. No specific age
threshold is intended" [2].
High-grade CIN is less likely to progress to cancer in young women and may regress [22,23,33,34]. The meta-analysis discussed
above found that women with CIN 2 who were younger than 30 years had a regression rate of 60 percent [22]. By contrast,
regression rates were somewhat lower across all women (50 percent at 24 months). For CIN 3, in women ages 20 to 24 years,
the estimated progression rate from CIN 3 to cancer in one year is 0.5 percent [35]. The rate increases with age, reaching 10
percent per year for women age 80 and older. (See 'Risk of malignant disease' above.)
Young women with CIN 2,3 are managed as follows (algorithm 6) [2,10]:
Either treatment or observation is acceptable if colposcopy is adequate. If the histology is CIN 2, observation is preferred, since
this diagnosis is associated with interobserver variability and may represent a less severe abnormality. If CIN 3 is present or
colposcopy is inadequate, treatment is preferred.
● Observation includes cytology and colposcopy every six months for 12 months.
• If cytology and colposcopy are negative for two visits, HPV and cytology cotesting should be performed one year later. If
cotesting is negative, cotesting should be performed in three years. Colposcopy should be performed if the two-year or
five-year cotest is abnormal.
• If the colposcopic appearance of the lesion worsens or if high-grade squamous intraepithelial lesion (HSIL) cytology or a
high-grade colposcopic lesion persists for one year, repeat biopsy is recommended.
• If CIN 2,3 persists for 24 months, treatment is the preferred approach.
● Alternatively, the patient may be treated with excision or ablation of the cervical transformation zone.
SPECIAL POPULATIONS
Pregnant women — Pregnant women with CIN 1 should not undergo cervical excision or ablation, regardless of the duration of
the abnormality and irrespective of whether the antecedent tests were high grade (atypical squamous cells, cannot rule out high
grade squamous intraepithelial lesion [ASC-H] or high-grade squamous intraepithelial lesion [HSIL]). The patient should be
reevaluated six weeks postpartum and managed based on those results.
For pregnant women with CIN 2,3, if invasive disease is not suspected, there are two options for follow-up [2,36-38]:
● Repeat evaluation with cytology and colposcopy during the pregnancy, but not more often than every 12 weeks. A biopsy
may be repeated only if the appearance of the lesion worsens or if cytology suggests invasive disease. Endocervical
sampling with a curette and endometrial sampling should NOT be performed, as there is a risk of disturbing the pregnancy.
● Alternatively, reevaluation may be deferred until six weeks postpartum.
A diagnostic excisional procedure is performed only if invasive disease is suspected (see "Cervical cancer in pregnancy"). High-
grade lesions discovered during pregnancy have a high rate of regression in the postpartum period. As an example, in one study,
70 percent of 153 women with CIN 3 had regression, and none progressed to invasive carcinoma [36]. This underscores the role
for conservative antepartum management followed by careful postpartum evaluation. Furthermore, the morbidity associated with
cervical conization during pregnancy is substantial.
Adolescents inadvertently screened — Cervical cancer screening should be started at age 21 years, according to guidelines
from the American College of Obstetricians and Gynecologists, the United States Preventive Services Task Force, the American
Society for Colposcopy and Cervical Pathology, the American Cancer Society, and the American Society for Clinical Pathology
(table 1). If adolescents are inadvertently screened, the management of abnormal results should follow the recommendations for
women ages 21 to 24. (See 'Women ages 21 to 24' above and 'Women ages 21 to 24' above and 'Young women' above and
"Screening for cervical cancer".)
This approach is conservative, since the incidence of cervical cancer in adolescents (0.15 per 100,000 females annually in one
Untied States study) is even lower than in women ages 21 to 24 (1.4 per 100,000) [12]. As with women ages 21 to 24, the rate of
human papillomavirus (HPV) infection is high and cervical intraepithelial lesions often regress spontaneously [13,14].
Immunocompromised women — Cervical cancer screening abnormalities (cytology or HPV testing) in women with
immunosuppressive conditions, including human immunodeficiency virus infection, should be managed in the same manner as
immunocompetent women [2]. (See "Screening for cervical cancer in HIV-infected women and adolescents", section on
'Evaluation of abnormal results'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Cervical cancer screening and prevention".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer
the four or five key questions a patient might have about a given condition. These articles are best for patients who want a
general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who
want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your
patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s)
of interest.)
● Beyond the Basics topics (see "Patient education: Management of a cervical biopsy with precancerous cells (Beyond the
Basics)" and "Patient education: Follow-up of low-grade abnormal Pap tests (Beyond the Basics)" and "Patient education:
Follow-up of high-grade or glandular cell abnormal Pap tests (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
● Cervical intraepithelial neoplasia (CIN) is a premalignant condition of the uterine cervix. CIN refers to squamous, not
glandular, abnormalities. (See 'Introduction' above.)
● There are two management approaches to CIN: observation (with cervical cytology, human papillomavirus [HPV] testing,
and colposcopy) and treatment with an excision or ablation of the cervical transformation zone (an anatomic area that
contains the transition from the squamous epithelium of the ectocervix to the glandular epithelium of the endocervix), or less
commonly, hysterectomy. (See 'Overview of management' above.)
● The management of CIN differs for women ages 21 to 24 years from that for women 25 and older because CIN often
regresses spontaneously in this patient population, and the risk of cervical cancer is low. In addition, some guidelines differ
for young women who plan future childbearing, since excisional treatments of the cervix are associated with obstetric risks in
future pregnancies. (See 'Women ages 21 to 24' above and 'Women ages 21 to 24' above and 'Young women' above.)
● The risk of malignancy with low-grade CIN (CIN 1) depends upon the preceding cervical cytology (see 'Risk of malignant
disease' above):
• For atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions
(LSIL), 4 to 13 percent of women will be diagnosed with CIN 2,3 within 6 to 24 months of follow-up.
• For atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) or high-grade
squamous intraepithelial lesions (HSIL), the five-year risk of CIN 3 or cervical cancer is approximately 15 percent.
● For most women with CIN 1, we suggest observation with cervical cancer screening tests rather than treatment (Grade 2C).
A cervical procedure for diagnosis and treatment is reasonable if CIN 1 is persistent for more than two years or if there is
suspicion of high-grade disease (preceding high-grade cytology). (See 'Low-grade lesions: CIN 1' above.)
https://www.uptodate.com/contents/cervical-intraepithelial-neoplas…earch_result&selectedTitle=1~150&usage_type=default&display_rank=1 Page 7 of 20
● For women ages 25 and older, CIN 1 preceded by lesser abnormalities (ASC-US, LSIL, HPV 16 or 18 infection detected with
HPV genotyping, or persistent HPV infection) is managed with observation with cotesting with cervical cytology and HPV
testing in 12 months. For women ages 21 to 24, management is observation with cytology alone in 12 months because the
rate of HPV infection is high in this patient population. (See 'Women ages 25 or older' above and 'Women ages 21 to 24'
above.)
● CIN 2,3 is associated with a high risk of cervical cancer. Five percent of CIN 2 lesions and 12 to 40 percent of CIN 3 lesions
will progress to cervical cancer. (See 'Risk of malignant disease' above.)
● For most women with CIN 2,3, we recommend treatment rather than observation (Grade 1B). Observation with cytology and
colposcopy is reasonable for women who are planning future childbearing and are able to comply with long-term testing.
Treatment is deferred for pregnant women, unless invasive disease is suspected.
Use of UpToDate is subject to the Subscription and License Agreement.
REFERENCES
1. Montz FJ. Management of high-grade cervical intraepithelial neoplasia and low-grade squamous intraepithelial lesion and
potential complications. Clin Obstet Gynecol 2000; 43:394.
2. Massad LS, Einstein MH, Huh WK, et al. 2012 updated consensus guidelines for the management of abnormal cervical
cancer screening tests and cancer precursors. J Low Genit Tract Dis 2013; 17:S1.
3. Waxman AG, Chelmow D, Darragh TM, et al. Revised terminology for cervical histopathology and its implications for
management of high-grade squamous intraepithelial lesions of the cervix. Obstet Gynecol 2012; 120:1465.
4. Darragh TM, Colgan TJ, Thomas Cox J, et al. The Lower Anogenital Squamous Terminology Standardization project for
HPV-associated lesions: background and consensus recommendations from the College of American Pathologists and the
American Society for Colposcopy and Cervical Pathology. Int J Gynecol Pathol 2013; 32:76.
5. Bansal N, Wright JD, Cohen CJ, Herzog TJ. Natural history of established low grade cervical intraepithelial (CIN 1) lesions.
Anticancer Res 2008; 28:1763.
6. Cox JT, Schiffman M, Solomon D, ASCUS-LSIL Triage Study (ALTS) Group. Prospective follow-up suggests similar risk of
subsequent cervical intraepithelial neoplasia grade 2 or 3 among women with cervical intraepithelial neoplasia grade 1 or
negative colposcopy and directed biopsy. Am J Obstet Gynecol 2003; 188:1406.
7. Castle PE, Gage JC, Wheeler CM, Schiffman M. The clinical meaning of a cervical intraepithelial neoplasia grade 1 biopsy.
Obstet Gynecol 2011; 118:1222.
8. Elit L, Levine MN, Julian JA, et al. Expectant management versus immediate treatment for low-grade cervical intraepithelial
neoplasia : a randomized trial in Canada and Brazil. Cancer 2011; 117:1438.
9. Katki HA, Gage JC, Schiffman M, et al. Follow-up testing after colposcopy: five-year risk of CIN 2+ after a colposcopic
diagnosis of CIN 1 or less. J Low Genit Tract Dis 2013; 17:S69.
10. http://www.asccp.org/ (Accessed on March 22, 2012).
11. Guido R, Schiffman M, Solomon D, et al. Postcolposcopy management strategies for women referred with low-grade
squamous intraepithelial lesions or human papillomavirus DNA-positive atypical squamous cells of undetermined
significance: a two-year prospective study. Am J Obstet Gynecol 2003; 188:1401.
12. Benard VB, Watson M, Castle PE, Saraiya M. Cervical carcinoma rates among young females in the United States. Obstet
Gynecol 2012; 120:1117.
13. Winer RL, Lee SK, Hughes JP, et al. Genital human papillomavirus infection: incidence and risk factors in a cohort of
female university students. Am J Epidemiol 2003; 157:218.
14. Moscicki AB, Hills N, Shiboski S, et al. Risks for incident human papillomavirus infection and low-grade squamous
intraepithelial lesion development in young females. JAMA 2001; 285:2995.
15. Schmeink CE, Massuger LF, Lenselink CH, et al. Prospective follow-up of 2,065 young unscreened women to study human
papillomavirus incidence and clearance. Int J Cancer 2013; 133:172.
16. Ferris DG, Litaker MS, ALTS Group. Prediction of cervical histologic results using an abbreviated Reid Colposcopic Index
during ALTS. Am J Obstet Gynecol 2006; 194:704.

17. Massad LS, Jeronimo J, Schiffman M, National Institutes of Health/American Society for Colposcopy and Cervical
Pathology (NIH/ASCCP) Research Group. Interobserver agreement in the assessment of components of colposcopic
grading. Obstet Gynecol 2008; 111:1279.
18. Massad LS, Collins YC. Strength of correlations between colposcopic impression and biopsy histology. Gynecol Oncol
2003; 89:424.
19. Melnikow J, Nuovo J, Willan AR, et al. Natural history of cervical squamous intraepithelial lesions: a meta-analysis. Obstet
Gynecol 1998; 92:727.
20. Robertson AJ, Anderson JM, Beck JS, et al. Observer variability in histopathological reporting of cervical biopsy
specimens. J Clin Pathol 1989; 42:231.
21. Mitchell MF, Tortolero-Luna G, Wright T, et al. Cervical human papillomavirus infection and intraepithelial neoplasia: a
review. J Natl Cancer Inst Monogr 1996; :17.
22. Tainio K, Athanasiou A, Tikkinen KAO, et al. Clinical course of untreated cervical intraepithelial neoplasia grade 2 under
active surveillance: systematic review and meta-analysis. BMJ 2018; 360:k499.
23. Castle PE, Schiffman M, Wheeler CM, Solomon D. Evidence for frequent regression of cervical intraepithelial neoplasia-
grade 2. Obstet Gynecol 2009; 113:18.
24. Nucci MR, Crum CP. Redefining early cervical neoplasia: recent progress. Adv Anat Pathol 2007; 14:1.
25. Chan JK, Monk BJ, Brewer C, et al. HPV infection and number of lifetime sexual partners are strong predictors for 'natural'
regression of CIN 2 and 3. Br J Cancer 2003; 89:1062.
26. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin number 66, September 2005. Management
of abnormal cervical cytology and histology. Obstet Gynecol 2005; 106:645.
27. McIndoe WA, McLean MR, Jones RW, Mullins PR. The invasive potential of carcinoma in situ of the cervix. Obstet Gynecol
1984; 64:451.
28. Gustafsson L, Adami HO. Natural history of cervical neoplasia: consistent results obtained by an identification technique.
Br J Cancer 1989; 60:132.
29. Peto J, Gilham C, Fletcher O, Matthews FE. The cervical cancer epidemic that screening has prevented in the UK. Lancet
2004; 364:249.
30. McCredie MR, Sharples KJ, Paul C, et al. Natural history of cervical neoplasia and risk of invasive cancer in women with
cervical intraepithelial neoplasia 3: a retrospective cohort study. Lancet Oncol 2008; 9:425.
31. Duggan BD, Felix JC, Muderspach LI, et al. Cold-knife conization versus conization by the loop electrosurgical excision
procedure: a randomized, prospective study. Am J Obstet Gynecol 1999; 180:276.
32. Fine BA, Feinstein GI, Sabella V. The pre- and postoperative value of endocervical curettage in the detection of cervical
intraepithelial neoplasia and invasive cervical cancer. Gynecol Oncol 1998; 71:46.
33. Moscicki AB, Schiffman M, Burchell A, et al. Updating the natural history of human papillomavirus and anogenital cancers.
Vaccine 2012; 30 Suppl 5:F24.
34. McAllum B, Sykes PH, Sadler L, et al. Is the treatment of CIN 2 always necessary in women under 25 years old? Am J
Obstet Gynecol 2011; 205:478.e1.
35. Herbert A, Holdsworth G, Kubba A. Why young women should be screened for cervical cancer: the distinction between
CIN2 and CIN3. Int J Cancer 2010; 126:2256.
36. Yost NP, Santoso JT, McIntire DD, Iliya FA. Postpartum regression rates of antepartum cervical intraepithelial neoplasia II
and III lesions. Obstet Gynecol 1999; 93:359.
37. Economos K, Perez Veridiano N, Delke I, et al. Abnormal cervical cytology in pregnancy: a 17-year experience. Obstet
Gynecol 1993; 81:915.
38. Connor JP. Noninvasive cervical cancer complicating pregnancy. Obstet Gynecol Clin North Am 1998; 25:331.
Topic 3215 Version 26.0
GRAPHICS
Human papillomavirus: High- and low-risk types for causing cervical cancer
High-risk (oncogenic or cancer-associated) types

Common types: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 69, 82
Low-risk (non-oncogenic) types

Common types: 6, 11, 40, 42, 43, 44, 54, 61, 72, 81
Data from: Centers for Disease Control and Prevention. National Cancer Institute Factsheet. Human papillomavirus and cancer: Questions
and answers. Available at: www.cancer.gov/cancertopics/factsheet/Risk/HPV (Accessed on June 11, 2012).
Graphic 76394 Version 6.0
Terminology and histology of cervical intraepithelial neoplasia
Terminology regarding cytologic and histologic precancerous changes of the uterine cervix. The corresponding terminology
from the previous classification systems is shown. Images of the histologic correlates for each category are also shown.
LAST: lower anogenital squamous terminology; LSIL: low-grade squamous intraepithelial lesions; HSIL: high-grade
squamous intraepithelial lesions; CIN: cervical intraepithelial neoplasia.
* CIN 2 that is p16-positive is classified as HSIL. CIN 2 that is p16-negative is classified as LSIL.
References:
1. Darragh TM, Colgan TJ, Thomas Cox J, et al. The Lower Anogenital Squamous Terminology Standardization project for
HPV-associated lesions: background and consensus recommendations from the College of American Pathologists and
the American Society for Colposcopy and Cervical Pathology. Int J Gynecol Pathol 2013; 32:76.
2. Solomon D, Davey D, Kurman R, et al. The 2001 Bethesda System: terminology for reporting results of cervical
cytology. JAMA 2002; 287:2114.
Management of Women with No Lesion or Biopsy-confirmed Cervical Intraepithelial Neoplasia—

Grade 1 (CIN1) Preceded by "Lesser Abnormalities"
Reprinted from: The Journal of Lower Genital Tract Disease Volume 17, Number 5, with the permission of ASCCP © American Society for
Colposcopy and Cervical Pathology 2013. No copies of the algorithms may be made without the prior consent of ASCCP.
Cervical cancer screening recommendations from United States professional organizations*
Recommended screening
Post-
Age to Age to test
hysterectomy HPV
Organization initiate discontinue and frequency
for benign vaccination
(years) (years) Age 21 to 29 Age ≥30 disease
(years) (years)
ACS/ASCCP/ASCP 21 ¶ 65 Δ Pap test every 3 One of these Not indicated ◊ Same

(2012) years methods: recommendations
(preferred) Co-testing as unvaccinated
(Pap test women
and HPV
testing)
every 5
years
(preferred)
Pap test
every 3
years
ASCCP/SGO 21 N/A Can consider Can consider N/A N/A

(2015 interim primary HPV primary HPV
guidelines) testing every 3 testing every 3
years for years
women age ≥25
USPSTF (2018) 21 65 § Pap test every 3 One of these Not indicated ¥ Same
years methods: recommendations
Pap test as unvaccinated
every 3 women
years
hrHPV
testing
alone
every 5
years
Co-testing
(Pap test
and HPV
testing)
every 5
years
ACOG (2016) 21 65 ‡ One of these One of these Not indicated † Same

methods: methods: recommendations
Pap test Co-testing as unvaccinated
every 3 (Pap test women
years and HPV
Can testing)
consider every 5
primary years
HPV (preferred)
testing Pap test
every 3 every 3
years for years
women Can
age ≥25 consider
primary
HPV testing
every 3
years for
women age
≥25
ACP (2015) 21 65 § Pap test every 3 One of these Not indicated ¥ N/A
years methods:
Pap test
every 3
years
Alternative:
Co-testing
(Pap test
and HPV
testing)
every 5
years
HPV: human papillomavirus; ACS: American Cancer Society; ASCCP: American Society for Colposcopy and Cervical Pathology; ASCP:
American Society for Clinical Pathology; SGO: Society of Gynecologic Oncology; USPSTF: United States Preventive Services Task Force;
ACOG: American College of Obstetricians and Gynecologists; ACP: American College of Physicians; hrHPV: high-risk human papillomavirus;
DES: diethylstilbestrol; HIV: human immunodeficiency virus; CIN: cervical intraepithelial neoplasia.
* These guidelines are intended for the general population and are not intended for women who have a history of cervical cancer, high-grade
cervical precancers, DES in utero exposure, or who are immunocompromised, as with HIV infection.
¶ Regardless of the age of sexual initiation or other risk factors.
Δ For women with evidence of adequate negative prior screening (3 consecutive negative cytology results or 2 consecutive negative co-tests
within the previous 10 years, with the most recent test within the previous 5 years) and no history of CIN 2 or greater within the last 20
years. Screening should not be resumed for any reason, even if a woman has a new sexual partner.
◊ For women who have had a benign hysterectomy with removal of the cervix who do not have a history of CIN 2, CIN 3 in the past 20
years, or a history of cervical cancer ever. Evidence of adequate negative prior screening not required.
§ For women with evidence of adequate negative prior screening, specified as 3 consecutive negative cytology results or 2 consecutive
negative co-tests within the previous 10 years, with the most recent test within the previous 5 years.
¥ For women who have had a benign hysterectomy with removal of the cervix who do not have a history of CIN 2 or higher.
‡ For women with no history of CIN 2 or higher with evidence of prior adequate screening (3 or more negative cytology test results in a row
or 2 consecutive negative co-tests in the past 10 years, with the most recent within the past 5 years).
† For women who have had a benign hysterectomy with removal of the cervix who do not have a history of CIN 2, CIN 3, or cervical cancer.
Women in whom a negative history cannot be documented should continue to be screened.
Reference:
1. Saslow D, Solomon D, Lawson HW, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and
American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. CA Cancer J Clin
2012; 62:147.Curry SJ. Screening for cervical cancer: United States Preventive Services Task Force recommendation statement. JAMA
2018; 320:674.
2. Cervical cytology screening. ACOG Practice Bulletin No. 157. American College of Obstetricians and Gynecologists. Obstet Gynecol
2016; 127:e1
3. Huh WK, Ault KA, Chelmow D, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: Interim
clinical guidance. Gynecol Oncol 2015; 136:178. http://dx.doi.org/10.1016/j.ygyno.2014.12.022.
4. Sawaya GF, Kulasingam S, Denberg TD, et al. Cervical Cancer Screening in Average-Risk Women: Best Practice Advice From the
Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med 2015; 162:851.
Management of Women Ages 21-24 with No Lesion or Biopsy-confirmed Cervical Intraepithelial

Neoplasia—Grade 1 (CIN1)
Management of Women with No Lesion or Biopsy-confirmed Cervical Intraepithelial Neoplasia—

Grade 1 (CIN1) Preceded by ASC-H or HSIL Cytology
Management of Women Ages 21-24 yrs with Atypical Squamous Cells, Cannot Rule Out High Grade
SIL (ASC-H) and High-grade Squamous Intraepithelial Lesion (HSIL)
Management of Women with Biopsy-confirmed Cervical Intraepithelial Neoplasia—Grade 2 and 3

(CIN2,3)
Management of Young Women with Biopsy-confirmed Cervical Intraepithelial Neoplasia—Grade 2,3

(CIN2,3) in Special Circumstances
Contributor Disclosures
Jason D Wright, MD Consultant/Advisory Boards: Tesaro [Gynecologic cancer (Drug development)]; Clovis Oncology
[Gynecologic cancer (Drug development)]. Barbara Goﬀ, MD Employment (Spouse): Lilly [General oncology (Gemcitabine,
pemetrexed)] - No relevant conflict on topics. Sandy J Falk, MD, FACOG Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting
through a multi-level review process, and through requirements for references to be provided to support the content.
Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
Conflict of interest policy
https://www.uptodate.com/contents/cervical-intraepithelial-neopla…arch_result&selectedTitle=1~150&usage_type=default&display_rank=1 Page 20 of 20

Cervical Cancer Management

Transféré par

Informations du document

Copyright

Formats disponibles

Partager ce document

Partager ou intégrer le document

Options de partage

Avez-vous trouvé ce document utile ?

Ce contenu est-il inapproprié ?

Droits d'auteur :

Formats disponibles

Cervical Cancer Management

Transféré par

Droits d'auteur :

Formats disponibles

Cervical intraepithelial neoplasia: Management of low-grade and high-grade lesions - UpToDate 3/27/19, 17)19

Official reprint from UpToDate®

Cervical intraepithelial neoplasia: Management of low-grade and high-grade lesions

Author: Jason D Wright, MD

Management of CIN is reviewed here. Related issues are discussed separately:

● Treatment of CIN (see "Cervical intraepithelial neoplasia: Treatment and follow-up")

● Cervical cancer screening (see "Screening for cervical cancer")

● CIN 3 is referred to as HSIL.

The outcome of CIN 1 lesions depends upon the preceding cytology:

● HPV/cytology cotesting should be performed in 12 months.

● Cytology should be repeated in 12 months.

● Patients may be managed in one of three ways:

• Alternatively, a diagnostic excisional procedure may be performed without further testing.

excision or ablation of the cervical transformation zone may be performed.

• If CIN 2,3 persists for 24 months, treatment is the preferred approach.

● Alternatively, reevaluation may be deferred until six weeks postpartum.

SUMMARY AND RECOMMENDATIONS

Use of UpToDate is subject to the Subscription and License Agreement.

during ALTS. Am J Obstet Gynecol 2006; 194:704.

Topic 3215 Version 26.0

High-risk (oncogenic or cancer-associated) types

Low-risk (non-oncogenic) types

Graphic 76394 Version 6.0

Terminology and histology of cervical intraepithelial neoplasia

Graphic 60116 Version 7.0

Management of Women with No Lesion or Biopsy-confirmed Cervical Intraepithelial Neoplasia—

Graphic 89364 Version 4.0

Cervical cancer screening recommendations from United States professional organizations*

ACS/ASCCP/ASCP 21 ¶ 65 Δ Pap test every 3 One of these Not indicated ◊ Same

ASCCP/SGO 21 N/A Can consider Can consider N/A N/A

ACOG (2016) 21 65 ‡ One of these One of these Not indicated † Same

Graphic 82951 Version 19.0

Management of Women Ages 21-24 with No Lesion or Biopsy-confirmed Cervical Intraepithelial

Graphic 89366 Version 4.0

Management of Women with No Lesion or Biopsy-confirmed Cervical Intraepithelial Neoplasia—

Graphic 89365 Version 4.0

Graphic 89360 Version 4.0

Management of Women with Biopsy-confirmed Cervical Intraepithelial Neoplasia—Grade 2 and 3

Graphic 89367 Version 4.0

Management of Young Women with Biopsy-confirmed Cervical Intraepithelial Neoplasia—Grade 2,3

Graphic 89368 Version 4.0

Conflict of interest policy

Vous aimerez peut-être aussi