Cervical cytology: Interpretation of results

Authors
Christine H Holschneider, MD
Christopher P Crum, MD
Section Editor
Barbara Goff, MD
Deputy Editor
Sandy J Falk, MD
Last literature review version 18.2: mayo 2010 | This topic last updated: mayo 27, 2010
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INTRODUCTION Cervical cytology became the standard screening test for cervical
cancer and premalignant cervical lesions with the introduction of the Papanicolaou
(Pap) smear in 1941 [1]. Liquid-based, thin layer preparation (eg, ThinPrep,
SurePath) of cervical cytology specimens was a subsequent modification in
technique. Terminology for reporting cervical cytology was standardized by the
Bethesda System in 1988 [2]. This system has been revised several times and the
current system was developed in 2001 (table 1) [3,4]. (See "Cervical cancer screening
tests: Techniques for cervical cytology and human papillomavirus testing".)

Interpretation of cervical cytology results will be reviewed here. Cervical cancer

screening strategies and techniques, as well as the follow-up of abnormal cytology
results and treatment of cervical intraepithelial neoplasia, are reviewed separately. (See
"Screening for cervical cancer" and "Cervical cancer screening tests: Techniques for
cervical cytology and human papillomavirus testing" and "Cervical cytology:
Evaluation of atypical squamous cells (ASC-US and ASC-H)" and "Cervical cytology:
Evaluation of low grade squamous intraepithelial lesions" and "Cervical cytology:
Evaluation of high grade squamous intraepithelial lesions" and "Cervical cytology:
Evaluation of atypical and malignant glandular cells" and "Cervical intraepithelial
neoplasia: Management".)

TERMINOLOGY FOR SQUAMOUS CELL ABNORMALITIES There have been

frequent modifications in the nomenclature used for classifying cytologic and histologic
cervical changes associated with human papillomavirus (HPV) infection and
precancerous lesions. The current classification system in the United States was
introduced with the Bethesda 1988 System [3].

The major shifts in terminology apply to squamous cell abnormalities. The

corresponding terms across the three current and previous terminology systems for
squamous cell abnormalities are shown in the table (figure 1).

Squamous cervical cytologic abnormalities (those detected with Pap tests) are reported
using the term cervical squamous intraepithelial lesions (CSIL). Specifying "cervical"
differentiates these lesions from anal squamous intraepithelial lesions, which use similar
terminology. (See "Anal intraepithelial neoplasia: Diagnosis, screening, and treatment".)

CSIL is stratified into two categories:

Low grade squamous intraepithelial lesion (LSIL)

 High grade squamous intraepithelial lesion (HSIL)

The shift in terminology to LSIL and HSIL was made in the Bethesda 1988 system in
recognition of the differing clinical course of these two levels of cellular change. LSIL,
especially in young women, is generally a transient HPV infection, whereas HSIL is
more likely to be associated with persistent HPV infection and a higher risk of
progression to cervical cancer [4,5].

Cytologic abnormalities must be further evaluated with colposcopy and biopsy. The
finding of LSIL versus HSIL on cytology does not constitute a diagnosis of cervical
intraepithelial lesion (CIN) 1 versus CIN 2 or 3, respectively. Cytologic findings may be
associated with a subsequent histologic finding that is either more or less severe.

Current terminology for histologic squamous cell abnormalities is discussed separately

(see "Cervical intraepithelial neoplasia: Definition, incidence, and pathogenesis",
section on 'Terminology'). Current terminology for glandular cell findings is described
in a section below (see 'Glandular cell abnormalities' below).

ROLE OF CERVICAL CYTOLOGY The results of cervical cytology tests cannot be

used to make a definitive diagnosis or initiate treatment. Rather, the test functions solely
to screen for cellular abnormalities that are associated with an increased risk for the
development of cervical cancer. Thus, it selects those women who should have further
evaluation, such as colposcopy and/or biopsy. Approximately 7 to 10 percent of women
who are screened require additional evaluation [6]. Treatment decisions are then made
based upon diagnostic results from histologic examination, usually from
colposcopically directed biopsies. (See "Cervical intraepithelial neoplasia:
Management".)

OVERVIEW OF THE CERVICAL CYTOLOGY REPORT The cervical cytology

report consists of (table 1):

A description of specimen type and test requested cervical or vaginal sample,

conventional Pap smear, liquid based cytology, and/or reflex HPV test

A description of specimen adequacy

A general categorization (optional) negative, epithelial cell abnormality, or

other

An interpretation/result either the specimen is negative for intraepithelial

lesions and malignancy (although organisms or reactive changes may be present)
or there is an epithelial cell abnormality as defined by the Bethesda 2001
classification or there is another finding. This latter category may indicate some
increased risk, as an example: endometrial cells in a woman over 40 years of age
[4].

A description of any ancillary testing or automated review that was performed

(eg, HPV, AutoPap)
 Educational notes and suggestions by the pathologist (optional)

SPECIMEN ADEQUACY Satisfactory cervical cytology is defined by the number

of squamous cells in the sample.

Satisfactory for evaluation Criteria for "satisfactory for evaluation" are:

Squamous cellularity conventional Pap smears must have at least 8000 to

12,000 well-visualized squamous cells; liquid-based preparations must have a
minimum of 5000 well-visualized squamous cells

Labeled specimen

Cellularity may be diminished in women who have been treated with pelvic radiation.
This information should be included in the cytology requisition, and the reporting of
results will depend on the clinical context and the ability of the laboratory to evaluate
the specimen [7].

Cervical cytology specimens that are designated "satisfactory for evaluation" may, in
addition, be described using what are referred to as "quality indicators". Quality
indicators include scant cellularity, partially obscuring blood or inflammation, poor
fixation, thickly smeared slides, and absence of endocervical or transformation zone
(EC/TZ) component [8].

Endocervical cell/transformation zone component A notation is made regarding the

presence or absence of an endocervical cell/transformation zone (EC/TZ) component,
but these cells are not required for a cervical cytology test to be classified as satisfactory
according to Bethesda 2001 criteria [4]. The criteria for an EC/TZ component is at least
10 well-preserved endocervical or squamous metaplastic cells; clusters of cells are not
required as they were in Bethesda guidelines prior to 2001.

The presence of metaplastic and endocervical cells gives an indication of the sampling
of the transformation zone of the cervix (junction of squamous and glandular cells,
generally at the external cervical os). The transformation zone is the area at greatest risk
for neoplasia [9]. The EC/TZ component is more likely to be absent in adolescents and
women older than 30 years, particularly postmenopausal women [10,11].

The clinical significance for cervical cancer screening of the absence of the EC/TZ
component in a cervical cytology specimen is controversial [7,10,12-15]. In specimens
that lack endocervical cells, cytologic evaluation yields a lower rate of cellular
abnormalities [10,12,14]. This was best illustrated in a prospective study of over 4000
women in whom cervical cytology specimens without an EC/TZ component were found
to have a significantly lower detection rate of epithelial abnormalities than specimens
with an EC/TZ component (11 versus 18 percent) [10].

Since cytologic abnormalities are the indication for further evaluation with colposcopy
and cervical biopsy, this raises the question of whether a histologic diagnosis of cervical
intraepithelial neoplasia (CIN) or cervical cancer will be missed in women in whom a
Pap test lacks an EC/TZ component. However, there appears to be no increase in the
development of high-grade CIN or cancer in these women [10,15-17].
When cervical cytology is repeated in women who have had a Pap test without an
EC/TZ component, data suggest that there is no increase in cellular abnormalities
compared with other women [10,18]. This was illustrated in the prospective study of
4000 women described in a preceding paragraph, repeat cytology performed after a
median of 60 days (range 13 to 991 days) showed no significant difference in the rate of
epithelial abnormalities in women without versus with an EC/TZ component on the
initial specimen [10].

In addition, longitudinal studies (six months to eight years of follow-up) of 40,000 to

60,000 women with a Pap test that was reported as negative for epithelial abnormalities
but lacked an EC/TZ component found no increase in histologic diagnoses of high-
grade CIN or cervical cancer compared with women with an EC/TZ component (in one
study, for high-grade CIN, 0.6 to 2.6 versus 2.9 per 1000 years of follow-up [15]; in the
other study, for high-grade CIN, 6.2 versus 6.1 per 1000 and for cervical cancer, 0.53
versus 0.54 per 1000 [17]).

On the other hand, the proportion of endocervical adenocarcinoma among all cervical
carcinomas is increasing. Since these cancers most commonly arise in the glandular
cells of the endocervix, it is plausible that the detection of such cancers may be reduced
in specimens that lack an EC/TZ component [19]. However, glandular abnormalities are
less common than squamous abnormalities and there are few data to support or refute
this concern [15,20].

The advent of testing for HPV strains that are associated with a high risk of cervical
neoplasia (table 2) has not clarified this issue. A potentially clinically important
subgroup is women with a negative cervical cytology specimen that lacks an EC/TZ
component who have negative cytology and a positive HPV test. It is unknown whether
abnormal endocervical cells may have been missed in these women [7]. It appears that
women with a negative Pap test and positive HPV appear to have an increased risk for
subsequent cervical neoplasia; however, studies of this issue do not report the rate of
Paps without an EC/TZ component [21]. (See "Screening for cervical cancer".)

For women with an inadequate EC/TZ component and a negative HPV test, the issue is
whether the lack of these cells decreases the sensitivity of the HPV test. Two
retrospective series from the same institution of over 26,000 negative cervical cytology
specimens that were tested for high-risk HPV found no significant difference in the
prevalence of HPV in specimens without or with an EC/TZ component (2.5 versus 2.2
percent) [11,22].

A task force of the American Society for Colposcopy and Cervical Pathology addressing
the issue of cervical cytology specimens lacking an EC/TZ zone recommended that
most women without an EC/TZ component be screened with a repeat Pap test in 12
months and not to wait longer for a repeat test, even for women who would otherwise
be candidates for less frequent screening. (See "Screening for cervical cancer", [7].
However, repeat cervical cytology in six months was advised in the following
situations:

A previous cervical cytology test result of atypical squamous cells of

undetermined significance (ASC-US) or worse without two subsequent negative
cervical cytology tests or a subsequent negative HPV test
 A previous cervical cytology test with an unexplained glandular abnormality

A positive test for a high risk HPV strain within the previous 12 months (table 2)

Inability to clearly visualize or sample the endocervical canal

Similar obscuring factor in consecutive Pap tests

Insufficient frequency of previous screening

Partially obscuring blood or inflammation A specimen is considered "partially

obscured" when 50 to 75 percent of the epithelial cells cannot be visualized [4].
Specimens in which more than 75 percent of the cells are obscured are designated
unsatisfactory (see 'Unsatisfactory for evaluation' below).

Women with partially obscuring blood or inflammation should have a repeat test in six
months if they meet any of the above risk criteria or have a similar factor obscuring
consecutive tests [23]. This includes women whose tests are otherwise satisfactory.

Unsatisfactory for evaluation Cervical cytology tests that are designated

"unsatisfactory for evaluation" for one of three reasons [4]:

Scanty cellularity

Obscuring inflammation or blood

Unlabeled or otherwise unable to be processed by the laboratory

The reason for finding a specimen in unsatisfactory is noted in the report. The criteria
for cellularity and obscuring inflammation or blood are noted in the preceding sections
(see 'Satisfactory for evaluation' above and 'Partially obscuring blood or
inflammation' above). Specimens that were not processed by the laboratory because
they were unlabeled or the vial or slide broke are distinguished from specimens
determined to be unsatisfactory after processing.

An unsatisfactory cervical cytology specimen is considered unreliable for the evaluation

of epithelial abnormalities. Whether women with unsatisfactory cervical cytology tests
are more likely to have intraepithelial lesions or cancer on follow-up than women with
satisfactory tests is controversial [24-26].

A task force of the American Society for Colposcopy and Cervical Pathology
recommended that most women with cervical cytology that was unsatisfactory for
evaluation be screened with a repeat Pap test within two to four months [7]. A short
interval between Pap tests (15 to 30 days) does not appear to affect sensitivity for
detection of cervical neoplasia. (See "Cervical cancer screening tests: Techniques for
cervical cytology and human papillomavirus testing", section on 'Interval between Pap
tests'.)
If the cells are obscured by inflammation and a specific infection is identified, treatment
should be given before repeating the Pap test. Therefore, in women with repeatedly
unsatisfactory cytology specimens as well as those with symptoms (eg, postcoital
bleeding, pelvic pain) or physical examination findings suggestive of cervical cancer
(eg, visible cervical lesion), additional clinical evaluation with colposcopy and/or
biopsies is appropriate. (See "Invasive cervical cancer: Epidemiology, clinical features,
and diagnosis", section on 'Clinical manifestations'.)

Women in with an unsatisfactory Pap test in whom the test was not indicated within an
appropriate screening protocol do not need to repeat the test. (See "Screening for
cervical cancer".)

GENERAL CATEGORIZATION This is an optional section where specimens are

noted as either "negative for intraepithelial lesion or malignancy", "epithelial cell
abnormality", or "other" [4]. Specimens designated as "other" include those that contain
no morphologic abnormalities, but the findings may indicate some increased cancer risk
(eg, endometrial cells).

INTERPRETATION/RESULT The specimen is reported as either "negative for

intraepithelial lesions or malignancy" or an epithelial cell abnormality is specified.
Reporting of non-neoplastic findings (eg, infection or inflammation) is optional and is
reported under the heading "other" [4].

Negative for intraepithelial lesion or malignancy These are specimens in which no

epithelial abnormality is identified.

Intraepithelial cell abnormalities Intraepithelial abnormalities associated with HPV

infection and cervical precancer or cancer (nuclear enlargement and granulation, the
presence of koilocytes, an increased nucleocytoplasmic ratio, and frequent mitoses) are
specified as defined by the Bethesda 2001 classification.

Epithelial cell abnormalities are classified as squamous or glandular (table 1). The term
"atypical epithelial cells" may be used for cases where a squamous versus glandular
origin cannot be determined.

The categories of epithelial cell abnormalities are discussed below. Follow-up for these
abnormalities can be found in the topic reviews listed with each category.

Squamous cell abnormalities

Atypical squamous cells (ASC) are categorized as either of undetermined

significance (ASC-US) or cannot exclude a high-grade squamous intraepithelial
lesion (ASC-H). The ASC-H category includes findings that are equivocal, but
likely consists of a mixture of true high-grade squamous intraepithelial lesions
and other findings that mimic such lesions. Approximately 5 to 10 percent of
ASC results are designated ASC-H [27-29]. (See "Cervical cytology: Evaluation
of atypical squamous cells (ASC-US and ASC-H)".)
 Low grade intraepithelial lesion (LSIL). The LSIL category includes changes
consistent with HPV, mild dysplasia, or CIN 1 (grade 1 cervical intraepithelial
neoplasia).

LSIL cervical cytologic specimens occasionally contain a few cells that are suspicious
for, but not diagnostic of, a high-grade squamous intraepithelial lesion. Retrospective
studies have found that these women have a significantly higher likelihood of a high
grade lesion on biopsy than other women with LSIL (approximately 30 versus 15
percent) [30,31]. Although this is not included in the Bethesda classification, some
experts report such cytology as LSIL with a statement regarding the presence of a
possible high grade abnormality (eg, cannot exclude a high grade lesion, some cells
suggestive high grade intraepithelial lesion, or LSIL-H). These women should undergo
colposcopy and endocervical sampling. In our practice, we manage these cases like
those with a cytologic diagnosis of HSIL. (See "Cervical cytology: Evaluation of low
grade squamous intraepithelial lesions".)

High grade intraepithelial lesion (HSIL). HSIL includes changes consistent with
moderate or severe dysplasia, CIN 2 or 3, and carcinoma in situ (CIS) and
should indicate if there are features suspicious for invasive disease. (See
"Cervical cytology: Evaluation of high grade squamous intraepithelial lesions".)

Squamous cell carcinoma. (See "Invasive cervical cancer: Epidemiology,

clinical features, and diagnosis".)

The LSIL category includes changes consistent with HPV, mild dysplasia, or CIN 1
(grade 1 cervical intraepithelial neoplasia). HSIL includes changes consistent with
moderate or severe dysplasia, CIN 2 or 3, and carcinoma in situ (CIS) and should
indicate if there are features suspicious for invasive disease.

Glandular cell abnormalities Glandular abnormalities on cytology are reported in the

Bethesda 2001 classification as follows [4]:

Atypical glandular cells (AGC). Endocervical, endometrial, or not otherwise

specified is noted. Upon further evaluation, either high-grade squamous or
glandular abnormalities are found in 10 to 39 percent of women with a finding
of AGC on cytology [32]. This replaces the previous term "atypical glandular
cells of undetermined significance".

Atypical glandular cells, favor neoplastic. Endocervical or not otherwise

specified is noted. This designation is for specimens that show features
suggestive of, but no sufficient for an interpretation of adenocarcinoma.

Endocervical adenocarcinoma in situ (AIS).

Adenocarcinoma.

The follow-up of glandular cervical abnormalities is discussed separately. (See

"Cervical cytology: Evaluation of atypical and malignant glandular cells".)
When glandular cell abnormalities are present, it should be noted whether there are
changes favoring neoplasia.

Other Findings that are nonneoplastic or are related to cancers other than cervical
cancer are noted as "other". The presence of endometrial cells in a woman 40 years of
age should be noted. Specimens may have additional findings that should be described,
such as infectious organisms or cellular changes associated with infection, reactive
cellular changes, atrophy, or glandular cells after hysterectomy.

Endometrial cells in a woman 40 years The Bethesda 2001 system reports the
presence of normal, cytologically benign-appearing exfoliated endometrial glandular
cells only in women 40 years of age [4]. These are reported regardless of the date of
the last menstrual period. Their presence may reflect physiologic shedding (especially in
the first half of the menstrual cycle), or shedding in response to a pathological process.
The cells are reported so that the clinician can determine the significance of the finding
in an individual patient.

Benign appearing endometrial cells are noted in up to 12 percent of Pap cervical

cytology tests performed over one year, more commonly in premenopausal than
postmenopausal women [33]. The frequency this finding in women who are older than
40 years or postmenopausal is 0.4 percent of specimens [34]. The prevalence is
significantly higher in liquid-based versus conventional cytology (0.9 versus 0.3
percent).

The prevalence of a finding of benign-appearing endometrial cells varies with the

menstrual cycle. Combined results from two large studies showed that benign appearing
endometrial cells are more likely to be identified on cervicovaginal cervical cytology
tests in the first 10 to 12 days of the menstrual cycle (prevalence 21 to 24 percent) than
in the remainder of the cycle (prevalence 2 percent) [35,36].

Large reviews of benign-appearing endometrial cells in women over age 40 have

reported that 7 to 16 percent of cervical cytology specimens with this finding were
associated with significant endometrial pathology (hyperplasia or carcinoma) upon
further evaluation [33,34]. In one of these reviews that included 22 studies, among
women with significant pathology, 79 percent also had abnormal bleeding [34].

Women over age 40 encompass both pre- and postmenopausal women. If symptoms of
endometrial cancer are present (abnormal uterine bleeding), the patient should undergo
endometrial sampling regardless of menopausal status.

In premenopausal women without abnormal bleeding, benign appearing endometrial

cells are rarely associated with significant pathology [37-43]. Thus, the 2006 Bethesda
recommendations suggest no further work-up for these patients [38]. In addition, we
offer endometrial sampling to those asymptomatic premenopausal women with benign
appearing endometrial cells who are at increased risk for endometrial cancer (eg, family
or personal history of ovarian, breast, colon, or endometrial cancer; tamoxifen use;
chronic anovulation; obesity [8]; estrogen therapy; prior endometrial hyperplasia;
diabetes) (table 3). (See "Endometrial cancer: Epidemiology, risk factors, clinical
features, diagnosis, and screening", section on 'Risk factors'.)
On the other hand, asymptomatic postmenopausal women with benign endometrial cells
are at higher risk of endometrial cancer. Therefore, endometrial assessment is
recommended for this age group [44].

Other types of malignancy The presence of any other types of malignant cells should
be described. As an example, the cervical cytology test may occasionally identify
malignant cells from the fallopian tube, ovary, peritoneal cavity, vulva, or vagina. This
should be kept in mind, especially in women with persistent AGC that remains
unexplained after cervical and endometrial evaluation. In these cases, referral to a
gynecologic oncologist is recommended.

Organisms The presence of infection does not preclude further evaluation of an

epithelial cell abnormality. When an infectious organism is identified or suggested, the
patient should be contacted to determine if she is symptomatic. Antibiotic therapy is
indicated for any symptomatic infection [45]. (See "Diagnostic approach to women with
vaginal discharge or vulvovaginal symptoms".)

Trichomonas Asymptomatic trichomonas infection should be treated if the

diagnosis is reasonably certain. Liquid-based cervical cytology for diagnosis of
trichomoniasis is more accurate than conventional Pap smears. The sensitivity,
specificity, and positive and negative predictive values of liquid-based cervical
cytology tests for trichomonas infection are 61, 99, 96, and 91 percent,
respectively [46]. Therefore, treatment of asymptomatic women with
trichomonads noted on liquid-based cervical cytology is a reasonable approach.
Conventional Pap smears have a high false positive rate for trichomonads.
Therefore, the diagnosis should be confirmed by wet prep in asymptomatic
women. However, if the wet prep is negative, then culture is indicated because
of the low sensitivity of wet prep for this organism. (See "Trichomonas
vaginalis".)

Bacterial vaginosis Cervical cytology is not a reliable diagnostic method for

bacterial vaginosis (BV) and women with a cytologic report of BV need
confirmation with clinical testing before treatment. Further, clinical diagnosis of
BV is not associated with CIN [47]. However, a cytologic report of BV occurs
10 times more commonly in women with versus without HSIL [48]. The clinical
significance of this finding is unknown. (See "Bacterial vaginosis", section on
'Diagnosis'.)

Herpes simplex Herpes simplex may produce characteristic cytopathologic

changes (multinucleated giant cells). (See "Epidemiology, clinical
manifestations, and diagnosis of genital herpes simplex virus infection".)

Actinomyces Actinomyces may be identified on cervical cytology tests,

typically in women who have an intrauterine device. (See "Approach to
intrauterine contraception".)

Chlamydia Chlamydia infection cannot be reliably diagnosed by cervical

cytology tests [49].
Other non-neoplastic findings

Reactive changes/inflammation Most patients with only reactive changes due

to inflammation will not have an organism identified on their cervical cytology
test. The cervical cytology sampling does not need to be repeated unless the
patient is HIV positive, in which case it should be repeated in four to six months.
(See "Screening for cervical cancer in HIV infected women".)

Hyperkeratosis Hyperkeratosis or parakeratosis on an otherwise negative

cervical cytology test is not a marker for significant CIN [45,50], and may be
related to infection or trauma with inflammation, such as from use of a
diaphragm. We do not perform colposcopy based on this finding. We repeat the
cervical cytology test in 6 to 12 months, depending upon whether the patient is
at increased risk for CIN, such as immunocompromised or age less than 30. If
hyperkeratosis persists, treatment with topical estrogen may resolve the finding,
but no treatment is necessary. (See "Cervical cytology: Evaluation of atypical
squamous cells (ASC-US and ASC-H)".)

FOLLOW-UP OF NORMAL CYTOLOGY Follow-up of patients with a normal

results on cytological screening, including those who test positive for high risk HPV
subtypes, is discussed elsewhere. (See "Screening for cervical cancer".)

TECHNIQUES FOR FOLLOW-UP OF ABNORMALITIES Patients with

significant cytological abnormalities need further evaluation, such as colposcopy or
HPV DNA testing.

Colposcopy After application of acetic acid, visual examination of the cervix under
magnification using a colposcope allows identification of specific areas with epithelial
changes. The most severely abnormal areas are biopsied to determine the histologic
diagnosis. This is an office procedure that is performed during a pelvic examination
without the need for anesthesia. (See "Colposcopy".)

Endocervical curettage Endocervical curettage (ECC) or sampling (ECS) using a

brush or curette is performed in patients with ASC-H, HSIL, AGC, adenocarcinoma in
situ (AIS), some cases of LSIL (see "Cervical cytology: Evaluation of low grade
squamous intraepithelial lesions", if ablative treatment is contemplated, and in those
with an unsatisfactory colposcopic examination. ECC is not performed in pregnancy.

Human papillomavirus testing HPV testing is used primarily in evaluation and

follow-up of women with ASC-US and in the secondary triage of AGC with an initial
negative work-up. (See "Cervical cytology: Evaluation of atypical squamous cells
(ASC-US and ASC-H)" and "Cervical cytology: Evaluation of atypical and malignant
glandular cells".)

HPV infection is the leading etiologic agent in the development of premalignant and
malignant lower genital tract disease. Premenopausal women who test positive for
certain types of HPV are at higher risk of cervical dysplasia, while those who are test
negative or have types of HPV DNA of low oncogenic potential are at low risk (table 2).
(See "Cervical intraepithelial neoplasia: Definition, incidence, and pathogenesis",
section on 'Role of human papillomavirus'.)
The most widely used, well-studied HPV test is the Hybrid Capture 2 HPV DNA Assay
(HC ll, Digene Corporation), which uses a probe mix for high risk HPV types 16, 18,
31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68; the test does not distinguish individual
HPV types and will occasionally detect an HPV that is not in the high risk probe set. In
research studies, high risk HPV types 16 and 18 are the viruses most frequently isolated
in cervical cancer tissue [51]. (See "Virology of human papillomavirus infections and
the link to cancer".)

Random cervical biopsies If colposcopy is not available, multiple random cervical

biopsies at the squamocolumnar junction can be useful. Such biopsies have increased
identification of CIN 2 or greater, even in women with no colposcopically detected
lesions [52]. There is only weak evidence that CIN occurs more often anteriorly and
posteriorly than laterally, so four quadrant biopsies should be obtained [53].

INFORMATION FOR PATIENTS Educational materials on this topic are available

for patients. (See "Patient information: Cervical cancer screening".) We encourage you
to print or e-mail this topic review, or to refer patients to our public web site,
www.uptodate.com/patients, which includes this and other topics.

SUMMARY AND RECOMMENDATIONS

Unsatisfactory cervical cytology tests should be repeated in two to four months.

(See 'Unsatisfactory for evaluation' above.)

Women with insufficient endocervical cells in an otherwise satisfactory

specimen can be screened with a repeat test in 12 months. Repeat testing in six
months is suggested for such women who have risk factors for cervical cancer.
(See 'Endocervical cell/transformation zone component' above.)

Intraepithelial abnormalities and glandular abnormalities require further

assessment to exclude cancer or a precancerous lesion. (See 'Intraepithelial cell
abnormalities' above.)

Infectious organisms may be identified as an incidental finding. Management

depends on factors such as whether the patient is symptomatic and the type of
infection. (See 'Organisms' above.)

For patients who are 40 years or older and have a cervical cytology test showing
benign appearing endometrial cells, we suggest an endometrial biopsy ONLY in
those who have symptoms of endometrial cancer (abnormal uterine bleeding) or
risk factors for endometrial cancer (eg, postmenopausal; family or personal
history of ovarian, breast, colon, or endometrial cancer; tamoxifen use; chronic
anovulation; obesity; estrogen therapy; prior endometrial hyperplasia); women
without these factors can continue routine gynecologic care. (See 'Endometrial
cells in a woman 40 years' above.)

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