31/8/2020 Screening for cervical cancer - UpToDate

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Screening for cervical cancer

Authors: Sarah Feldman, MD, MPH, Annekathryn Goodman, MD, MPH, MS, Jeffrey F Peipert, MD, PhD
Section Editors: Barbara Goff, MD, Joann G Elmore, MD, MPH
Deputy Editors: Lisa Kunins, MD, Alana Chakrabarti, MD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jul 2020. | This topic last updated: Apr 21, 2020.

INTRODUCTION

Cervical cancer is common among women worldwide. Most cases occur in developing countries [1]. In
developed countries, the decreases in cervical cancer incidence and mortality rates are related to the
availability of screening and to human papillomavirus (HPV) vaccination programs.

Screening can detect precursors and early-stage disease for both types of cervical cancer: squamous
cell carcinoma and adenocarcinoma. Treatment of precursors and early-stage disease can prevent the
development of invasive cervical cancer and reduce cervical cancer mortality.

Cervical cancer screening began with the development of the Papanicolaou (Pap) test. In countries that
adopted Pap test screening, the incidence and mortality of cervical cancer have decreased. In addition to
the Pap test, screening methods now include tests for high-risk strains of HPV, which are central to the
pathogenesis of cervical cancer. Infection with high-risk strains of HPV and persistence of HPV infection
are the most important determinants of progression to cervical cancer [2-6].

Recommendations for screening, as well as specific screening strategies, balance the benefits from early
detection of treatable lesions and reduction in incidence and mortality of cervical cancer with potential
risks for false positives, unnecessary procedures, and other harms. Potential benefits and risks vary with
age, medical history, and risk factors.

There is debate about whom to screen, which testing methods are preferable (Pap test, HPV testing, or
both), and how often to screen.

This topic will discuss screening in developed countries, including appropriate ages to initiate and
discontinue screening, frequency of screening, and screening methods.

The 2019 American Society of Colposcopy and Cervical Pathology (ASCCP) Risk-Based Management
Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors were
released in April 2020 [7,8]. In addition, new cervical cancer screening guidelines are expected from the

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American Cancer Society (ACS) in 2020. This topic is undergoing revision based upon these guidelines,
and the new information will be available shortly.

Screening in resource-limited settings is described in detail separately. (See "Screening for cervical
cancer in resource-limited settings".)

Techniques for performing screening tests, interpreting tests, screening women who are HIV-positive,
and information about invasive cervical cancer are discussed in detail separately.

● (See "Cervical cancer screening tests: Techniques for cervical cytology and human papillomavirus
testing".)
● (See "Cervical and vaginal cytology: Interpretation of results (Pap test report)".)
● (See "Screening for cervical cancer in HIV-infected women and adolescents".)
● (See "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis".)

SCREENING AVERAGE-RISK WOMEN

The age to initiate screening and the frequency of screening may vary depending on a patient’s
screening history and whether or not a patient is immunosuppressed.

Screening recommendations for women who are at average risk for cervical cancer apply to women who
are asymptomatic, immunocompetent, and had adequate screening starting at age 21 years with results
that were all normal.

However, women at higher risk due to a history of prior abnormal screening results or
immunosuppression may need more frequent testing, based on their prior results and treatment. (See
'Screening in higher-risk women' below and 'Screening in other populations' below.)

Age less than 21 years — We suggest not screening asymptomatic immunocompetent women younger
than age 21 years, regardless of the age of initiation of sexual activity.

Observational studies suggest that the potential harms outweigh the potential benefits in this age group,
due to their low incidence of cervical cancer [9]. The age-adjusted incidence of cervical cancer in women
ages 15 to 19 years in the United States is 0.1 per 100,000 (figure 1) [10]. Adolescents are also more
likely to spontaneously clear human papillomavirus (HPV) infection and associated abnormalities. While
rates of atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous
intraepithelial lesions (LSIL) are consistently higher in adolescent women than in adults, 90 to 95 percent
of low-grade lesions in adolescent women, as well as many high-grade lesions, regress spontaneously
[11-15].

Age 21 to less than 30 years — We recommend cervical cancer screening in asymptomatic women age
21 years and older. We suggest initiating screening at age 21 for women who are immunocompetent,
regardless of the age of initiation of sexual activity [16].

Guidelines in the United States recommend initiating screening at age 21 years (table 1) [6,17,18]. Other
countries may initiate screening at different ages (usually between 20 and 25 years) [19]. International

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guidelines vary.

Women should be screened even if they report sexual abstinence. Women may have a variety of
reasons for not disclosing prior sexual activity, including social, religious, or cultural norms or
expectations regarding modesty, virginity, and shame as well as reluctance to acknowledge prior sexual
abuse or rape [20]. Women who have been sexually abused or raped are often reluctant to acknowledge
this history, and abuse may underlie the decision to abstain and not engage in subsequent sexual
activity. Furthermore, HPV can be transmitted in skin-to-skin genital touching, which patients may not
consider as sexual activity.

In women age 21 to <30 years with a normal immune system and prior results (if any) that are all normal:

● We suggest screening with Papanicolaou (Pap) testing. Some clinicians do Pap testing alone,
whereas others do a Pap test with reflex to HPV testing. If the Pap test is negative, screening should
be repeated at intervals of every three years.

● We suggest not screening women <30 years with primary HPV testing or co-testing [16].

Each of these screening strategies is described in detail below. (See 'Screening strategies' below.)

Infection with HPV may be transient and cervical dysplasia may regress spontaneously, particularly in
young women; thus, the poor specificity and correspondingly poor positive predictive value of HPV
testing limit its usefulness as a screening modality in this age group [18]. Therefore, primary HPV testing
is generally not used for screening under age 25 years, and in the US Preventive Services Task Force
(USPSTF) guideline it is not suggested until age 30 years, although the American Society for Colposcopy
and Cervical Pathology (ASCCP)/Society of Gynecologic Oncology (SGO) and the American College of
Obstetricians and Gynecologists (ACOG) guidelines consider it for women age ≥25 years [21,22].
Randomized trials have demonstrated that primary HPV testing in women <30 years of age results in
substantial detection of transient HPV infections and unnecessary colposcopies [23-25]. (See 'Cervical
disease detection and incidence' below and 'False-positive and colposcopy rates' below.)

Guidelines in the United States recommend various screening strategies for women <30 years (table 1)
[6,17,18]. International guidelines vary. World Health Organization (WHO) guidelines for screening for
cervical cancer prevention are available.

Age 30 years or older — We recommend ongoing cervical cancer screening in asymptomatic women in
this age group. Women who report sexual abstinence also require screening as discussed above.

There are several appropriate screening strategies for average-risk women age ≥30 years who are
immunocompetent.

For patients with normal results, we suggest screening with one of the following strategies at the
indicated frequency (specific testing and frequency are described in detail elsewhere (see 'Screening
strategies' below)):

● Co-testing (Pap test and HPV testing) every five years; or

● Primary HPV testing every five years; or

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● Pap test with reflex HPV testing every three years; or

● Pap test alone every three years

Patients with abnormal, unsatisfactory, or satisfactory but limited findings require further follow-up. (See
'Follow-up results that are not normal' below.)

The USPSTF 2018 recommendations added primary HPV testing to Pap testing alone or co-testing as
another screening strategy for women aged 30 to 65 years [21]. The USPSTF concluded that for primary
HPV testing alone, an interval of five years offers the best balance of benefits and harms; other specialty
society guidelines specify an interval of no sooner than every three years for primary HPV testing [21,22].
Recommendations from guideline-issuing organizations in the United States and specialty societies
around the world vary and are summarized in the table (table 1) and in the Society Guideline Links
section [6,17,18,21,26,27]. (See "Society guideline links: Cervical cancer screening and prevention".)

There are not high-quality data that indicate that one screening strategy is clearly superior to another
with regard to clinical outcomes. HPV infection is more likely to be persistent in women ≥30 years than in
younger women and has a greater likelihood of clinical significance than in younger age groups [28].
However, in this age group, it remains important to consider both the higher rate of detection of cervical
disease with HPV testing (alone or with Pap testing) compared with Pap testing alone as well as the
increase in false positives and in colposcopies associated with HPV testing. These are discussed in
detail below. (See 'Benefits and harms of screening' below.)

WHEN TO DISCONTINUE SCREENING

The decision to discontinue screening depends on the patient’s prior results, life expectancy, and
preferences in a shared decision-making discussion.

If adequate prior screening — Discontinuing screening is predicated upon having adequate prior
screening and having no previously abnormal results or immunosuppression. (See 'Continuing
surveillance after precancer or cancer' below and 'Other higher-risk patients' below.)

● For women with adequate prior screening with normal results and a life expectancy >10 years, the
optimal age to discontinue screening is uncertain.

● For women who have adequate prior screening and no factors that warrant extended screening, we
screen through age 65 years. While data are limited and potential harms of screening need to be
considered (eg, false positives), some clinicians continue to offer screening through age 74 years.

Adequate prior screening takes into account the number and timing of consecutive screening tests done
in the past 10 years and the results of those tests. To meet these criteria, Papanicolaou (Pap) tests must
be negative (ie, not abnormal, positive, unsatisfactory, or satisfactory but limited).

We consider adequate prior screening to be [17]:

● Two consecutive negative co-tests (Pap tests with human papillomavirus [HPV] testing) within the
past 10 years, with the most recent test within the previous five years; or

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● Three consecutive negative Pap tests within the past 10 years, with the most recent test within the
previous three years; or
● Two consecutive negative primary HPV tests within the past 10 years, with the most recent test
within the previous five years

If the results of screening within the prior 10 years are not known, then prior screening is not considered
adequate.

A patient with a history of high-grade cervical dysplasia (cervical intraepithelial neoplasia [CIN] 2/3 or
adenocarcinoma in situ [AIS]), cervical cancer, precancer or cancer of the vagina or vulva, or anal
intraepithelial neoplasia (AIN) should continue screening according to recommendations for surveillance
after these precancerous or cancerous findings. (See 'Continuing surveillance after precancer or cancer'
below.)

In the United States, guideline-issuing organizations recommend discontinuing screening after age 65 for
women who are up to date on testing with normal results (table 1). However, guidelines from some
countries use an older age at which to stop screening. For example, in Australia, which has the lowest
cervical cancer mortality rate in the world, guidelines advise discontinuing screening after age 74 years
[29]. The decision to discontinue screening should also consider the patient’s preferences in a shared
decision-making discussion.

Data about stopping age for cervical cancer screening are limited. A 2013 systematic review of 24
studies found no conclusive evidence to support a specific age to stop cervical cancer screening, as
none of the reviewed studies looked specifically at this question [30]. Observational studies suggest that
continued screening in older women may be efficacious [31-33].

Studies have reported an incidence of cervical cancer among women over age 65 years that is higher
than previously thought [34-36]. In a study that corrected for the estimated prevalence of hysterectomy,
cervical cancer incidence in the United States peaked at ages 65 to 69 years (corrected rate of 27.4
cervical cancer cases per 100,000 women versus uncorrected rate of 14.8 per 100,000 women). In one
study based on the Massachusetts state cancer registry, almost 24 percent of cervical cancers were
diagnosed in women age ≥65 years [37]. These older women were more likely to have higher-stage
disease (≥stage II) than younger women (72 versus 44 percent). In other studies, close to 20 percent of
cervical cancers occurred in women ages 65 years and above [34,35]; invasive cervical cancer incidence
did not decline with increasing age until at least age 85 years [36].

One limitation among the aforementioned studies is that it is uncertain whether the women who
developed cervical cancer at an older age had been adequately screened through age 65 years; thus,
the studies’ implications are not necessarily applicable to women over age 65 years whose prior
screening was adequate and negative. In average-risk women over age 65 years who have undergone
adequate prior screening with normal results, the harms of screening may outweigh the benefits [38,39].
Older women are less likely to realize the benefits of screening because of competing causes of death.
High-grade lesions are rare among older women who have been previously screened, and Pap test
abnormalities among previously screened older women may have poor positive predictive value for
significant pathology, while causing a need for follow-up testing [40,41]. A study in pre- and

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postmenopausal women who had Pap tests showing “atypical squamous cells: cannot exclude high-
grade lesion (ASC-H)” found high-grade histology in 22 percent of premenopausal women, compared
with 6 percent of postmenopausal women [42].

If prior screening inadequate or unknown — Women aged 65 years and older who have not had
adequate prior screening should undergo screening (see 'If adequate prior screening' above). Women
aged 65 years or older who have never been screened have the highest incidence of and mortality from
cervical cancer and benefit the most from screening [43-45]. Modeling studies suggest that screening
older women who have never been screened could reduce mortality by 74 percent [28].

For such patients, we suggest co-testing annually for three years before spreading out the interval to
every five years. Some clinicians continue screening such women up to about age 80 years. The
decision about how long to continue screening should be predicated on a life expectancy of at least 10
years and an informed decision–making discussion with the patient. (See 'If adequate prior screening'
above.)

For older women with inadequate or unknown prior screening, the US Preventive Services Task Force
(USPSTF) suggests that screening be continued until age 70 or 75 years [18].

A considerable proportion of older women have not had adequate prior screening [36]. In retrospective
analysis of United States survey data, 18 percent of women aged 61 to 65 years had not had a Pap test
within the preceding five years (including those who had never had a Pap test); thus, these women would
not meet criteria for stopping screening at age 65.

Other higher-risk patients — For most women who had prior abnormal screening results or are
immunosuppressed and who have a life expectancy >10 years, some contributors continue to offer
screening until about age 80 years, whereas others stop screening a few years earlier. The age to
discontinue screening depends on the adequacy of prior screening as well as on the patient’s risk factors
for cervical cancer.

Continuing surveillance may be warranted for women with a history of cervical, vaginal, or vulvar cancer
or precancerous findings, or AIN. (See 'Continuing surveillance after precancer or cancer' below.)

SCREENING IN HIGHER-RISK WOMEN

Factors that affect risk for cervical cancer and increase the recommended frequency and/or duration of
screening include persistence of infection with a high-risk strain of human papillomavirus (HPV), prior
abnormal screening results, a history of inadequate screening for cervical cancer, and
immunosuppression that can hinder clearance of HPV infection [46]. (See 'Follow-up results that are not
normal' below and "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and
diagnosis", section on 'Risk factors' and "Invasive cervical adenocarcinoma", section on 'Epidemiology
and risk factors'.)

HIV — Women with HIV are more likely to have persistent HPV infection and increased rates of high-
grade cervical dysplasia, and they are at increased risk for the development of cervical cancer.

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Screening for women infected with HIV is described separately. (See "Screening for cervical cancer in
HIV-infected women and adolescents".)

Immunosuppressive therapy — Women without HIV who are on long-term immunosuppressive therapy
(eg, for organ transplant or systemic disease) have decreased rates of clearance of HPV infection and
increased rates of cervical dysplasia and cancer [47].

For women who are immunocompromised from causes other than HIV, we initiate screening one year
after the onset of sexual activity or by age 21, whichever comes first, and screen for three years with a
yearly Papanicolaou (Pap) test for patients age <30 years and with a yearly Pap test, yearly reflex
testing, or yearly co-testing for patients age ≥30 years. If all results are normal for three years, these
patients may consider moving to a screening frequency of every three years but are not candidates for
screening every five years. Extending screening for cervical cancer is warranted beyond age 65 years in
patients who are on long-term immunosuppressive therapy, although data are limited. (See 'When to
discontinue screening' above.)

For example, rates of abnormal Pap tests, high-grade dysplasia, and persistence of high-risk HPV
subtypes are significantly higher in women with systemic lupus erythematosus who are receiving
immunosuppressive therapy than in patients on immunosuppressive treatment for other conditions or in
those with milder forms of lupus who are not on treatment [46,48-51].

Diethylstilbestrol-exposed women — Daughters of women who took diethylstilbestrol (DES) during

pregnancy should have more frequent screening for vaginal and cervical cancer. This is discussed
elsewhere. (See "Outcome and follow-up of diethylstilbestrol (DES) exposed individuals", section on
'Clinical follow-up for DES daughters'.)

Continuing surveillance after precancer or cancer — Precancerous cervical abnormalities and

carcinoma in situ may require extended surveillance. Extended cervical testing may also be warranted as
part of follow-up of HPV-related diseases of other pelvic organs (ie, vagina, vulva, and anus)

● History of cervical intraepithelial neoplasia (CIN) 2, CIN 3, cervical adenocarcinoma in situ (AIS),
vaginal intraepithelial neoplasia (VaIN), vaginal cancer, vulvar intraepithelial neoplasia (VIN), vulvar
cancer, or anal intraepithelial neoplasia (AIN). Subsequent surveillance and follow-up for women
who have a history of precancer or cancer of the cervix, vagina, or vulva, or AIN is discussed
elsewhere.

• (See "Cervical intraepithelial neoplasia: Choosing excision versus ablation, and prognosis and
follow-up after treatment", section on 'Evidence'.)
• (See "Cervical adenocarcinoma in situ", section on 'Monitoring post-hysterectomy'.)
• (See "Cervical adenocarcinoma in situ", section on 'Monitoring post-excisional procedure'.)
• (See "Vaginal intraepithelial neoplasia", section on 'Posttreatment surveillance'.)
• (See "Vaginal cancer", section on 'Post-treatment surveillance'.)
• (See "Vulvar squamous intraepithelial lesions (vulvar intraepithelial neoplasia)", section on
'Posttreatment surveillance'.)

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• (See "Squamous cell carcinoma of the vulva: Medical therapy and prognosis", section on
'Surveillance'.)
• (See "Anal squamous intraepithelial lesions: Diagnosis, screening, prevention, and treatment",
section on 'Posttreatment surveillance'.)

● Prior hysterectomy for CIN – Posthysterectomy screening in women with a history of CIN 2 or CIN
3 is discussed in detail separately. (See "Cervical intraepithelial neoplasia: Choosing excision versus
ablation, and prognosis and follow-up after treatment", section on 'Type and duration of testing'.)

● Invasive cervical cancer – Posttreatment surveillance is described in detail separately. (See

"Invasive cervical cancer: Patterns of recurrence and post-treatment surveillance".)

SCREENING IN OTHER POPULATIONS

Prior benign hysterectomy — Women who have a history of cervical neoplasia require surveillance
even after hysterectomy. (See "Cervical intraepithelial neoplasia: Choosing excision versus ablation, and
prognosis and follow-up after treatment", section on 'Type and duration of testing'.)

For patients who have had a hysterectomy and have no history of cervical cancer or cervical
intraepithelial neoplasia (CIN) our recommendations are:

● Total hysterectomy (with cervix removed) – We recommend that women who have undergone
total hysterectomy and have no history of cervical cancer or CIN NOT undergo screening for cervical
cancer or screening for vaginal cancer.

Women who have undergone a hysterectomy in which the cervix was removed are at a vanishingly
small risk of cervical cancer [52]. Although it was once believed that women without a uterus were at
increased risk for vaginal cancer [53-57], studies show no association between total hysterectomy
for benign disease and subsequent vaginal carcinoma [57-62].

● Subtotal hysterectomy (cervix intact) – Women who have undergone subtotal hysterectomy and
have no history of CIN likely share the same risk of cervical cancer as women with an intact uterus
and cervix, and screening recommendations are the same. (See 'Screening average-risk women'
above and 'Screening in higher-risk women' above.)

Women who are uncertain if their cervix was removed at the time of a benign hysterectomy should
undergo an examination to determine if the cervix is present; if so, there is ongoing need for cervical
cancer screening.

Recipients of HPV vaccine — Until data from clinical trials are available, current standard screening
recommendations should be observed for women who have received human papillomavirus (HPV)
vaccine [6,17,18,63,64]. (See 'Screening average-risk women' above and 'Screening in higher-risk
women' above.)

The optimal approach to cervical cancer screening in women who have received HPV vaccine or whose
male partners received HPV vaccine remains uncertain [65]. HPV vaccination of female and male

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adolescents is anticipated to have a significant impact on the risks for cervical abnormalities [66,67].
However, the vaccine does not provide immunity against all HPV types responsible for cervical cancers;
additionally, some vaccine recipients may have already been infected with high-risk HPV [63].

Resource-limited settings — For women in resource-limited settings, screening recommendations may

differ. This is discussed separately. (See "Screening for cervical cancer in resource-limited settings".)

Symptomatic women — Women of any age, including age <21 years, who have signs or symptoms of
cervical disease (eg, abnormality on visualization or palpation of the cervix, abnormal or postmenopausal
bleeding, abnormal discharge, pelvic pain, or change in bowel or bladder function) should undergo
appropriate diagnostic evaluation regardless of prior screening history. This evaluation includes a
diagnostic Papanicolaou (Pap) test and evaluation for cervical biopsy; by definition, this diagnostic
evaluation is not "screening" and may require additional follow-up. (See "Invasive cervical cancer:
Epidemiology, risk factors, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.)

SCREENING METHODS

Available screening tests — The available methods for screening are the Papanicolaou (Pap) test
(cytology) and human papillomavirus (HPV) testing [68]. These are used alone or in combination. (See
'Screening strategies' below.)

● Pap test – The Pap test consists of cells sampled from the cervix and vagina. It can identify
abnormal cells from the transformation zone and the junction of the ecto- and endocervix, where
cervical dysplasia and cancers arise. Sample collection is discussed elsewhere. (See "Cervical
cancer screening tests: Techniques for cervical cytology and human papillomavirus testing", section
on 'How to obtain a sample'.)

The Pap test yields cytologic results, permitting examination of cells (picture 1 and picture 2) but not
tissue structure. Interpretation of Pap test results is discussed elsewhere. (See "Cervical and vaginal
cytology: Interpretation of results (Pap test report)".)

In a systematic review, sensitivity and specificity varied significantly [69]. There is considerable
interobserver variability in test interpretation, although variability decreases for tests with more
severe abnormalities [70]. The Pap test is more sensitive for detecting squamous malignancy than
adenocarcinoma and adenocarcinoma in situ (AIS) [71,72]. Squamous lesions are more likely to be
visually apparent than adenocarcinoma. Also, adenocarcinoma involves the glandular tissue of the
internal cervical canal and may occur at several sites within the canal ("skip lesions"). This makes it
more difficult to detect by routine Pap screening.

Either conventional or liquid-based Pap tests are acceptable for cervical cancer screening [6]. These
are described separately. (See "Cervical cancer screening tests: Techniques for cervical cytology
and human papillomavirus testing", section on 'Specimens for cytology'.)

For a Pap test to be satisfactory for evaluation, an adequate number of squamous cells must be
present and well-visualized, not limited by obscuring factors or interfering substances. The absence

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of an endocervical transformation zone limits the quality of the sample but does not render the
specimen unsatisfactory. A Pap test that is satisfactory but limited by any of these factors warrants
additional evaluation and follow-up, which are described separately. (See "Cervical and vaginal
cytology: Interpretation of results (Pap test report)", section on 'Specimen adequacy'.)

● HPV testing – HPV tests identify most, but not all, of the high-risk HPV types (table 2). Four HPV
tests are approved by the US Food and Drug Administration (FDA) (table 3) [73]. Within this topic
review, "HPV testing" refers to the approved tests. Some researchers and clinicians use the term
“high-risk HPV” (“hrHPV”) testing when describing this HPV testing. One test, the cobas HPV test,
has been approved by the FDA for primary HPV testing (without a Pap test) in women age ≥25
years [74]. Three additional tests are approved for use in co-testing or reflex testing with a Pap test
(table 3). Other HPV tests may be used by individual laboratories but are not approved by the FDA
and have not been validated adequately.

Techniques for HPV testing are discussed separately. (See "Cervical cancer screening tests:
Techniques for cervical cytology and human papillomavirus testing", section on 'HPV testing'.)

The FDA approved the cobas test for primary HPV testing based on unpublished data from a large
multicenter prospective study in which women who had abnormal primary HPV testing were triaged
to have a Pap test and then colposcopy if the Pap test was abnormal [75,76].

Screening strategies — Screening strategies use the available screening tests (ie, Pap test, HPV
testing) either alone or in combination. (See 'Available screening tests' above.)

Management of screening results includes review of results of prior screening and any follow-up done;
these are needed to determine if follow-up testing is due and to guide the frequency of screening.

If results from the most recent or prior tests are abnormal, unsatisfactory, or satisfactory but limited,
additional follow-up of the findings is needed. The timing of follow-up depends upon the results of the
testing. (See 'Follow-up results that are not normal' below.)

If the most recent and all prior results are normal, and the patient is immunocompetent and up to date
with screening, screening strategies and frequencies include:

● Pap testing alone – In Pap testing alone, only a Pap test is done to assess cervical cytology for
cellular abnormalities. (See 'Available screening tests' above.)

When the Pap test is used as the only screening method and results of the Pap test and all prior
results are normal, we suggest screening every three years.

The incidence of high-grade cytologic abnormalities is very low within three years of a normal Pap
test (10 to 66 per 10,000) [38], and modeling studies have suggested cancer detection rates to be
similar with annual or triennial screening, while doubling or tripling the number of downstream
interventions, including colposcopies [77-79]. A synthesis of several studies in women aged 21 to 29
years predicted that the lifetime risk of death due to cervical cancer would be similar: 0.03, 0.05, and
0.05 per 1000 women with screening annually, every two years, and every three years, respectively
[17].
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● Reflex HPV testing (also called triage HPV testing) – In reflex testing, a Pap test is performed
first. If the Pap test shows atypical squamous cells of undetermined significance (ASC-US), an HPV
test is performed on a sample collected at the same time as the cytology was obtained, typically
using the same container.

With reflex HPV testing, if the Pap test is normal (thus HPV testing is not done) and all prior
screening results are normal, screening is suggested again in three years, as discussed above.

● Co-testing – In co-testing, both a Pap test and HPV testing are performed on the sample collected,
rather than using the result of the Pap test to determine if the HPV test should be done.

If co-testing is used and results of both tests are negative, and all prior results have been normal, a
co-testing screening interval of five years provides a balance of benefits and risks that is comparable
to cytology screening every three years.

A US Preventive Services Task Force (USPSTF) review of four randomized trials found a similar
number of detected cancer cases with co-testing at a frequency of every five years compared with
Pap testing alone every three years, although differences in study methodology (colposcopy referral
methods and thresholds) made interpretation complex [18].

● Primary HPV testing – In primary HPV testing, an HPV test alone is performed. In many countries,
although not in most United States settings, primary HPV testing is used, especially when Pap
testing is not available and/or resources are limited.

If HPV testing is used as the only screening method (primary HPV testing) and is negative (normal),
Society of Gynecologic Oncology (SGO)/American Society for Colposcopy and Cervical Pathology
(ASCCP) guidelines state that rescreening should occur no sooner than every three years, whereas
the USPSTF recommends screening every five years.

In the Athena trial, with three-year follow-up, the cumulative incidence of cervical intraepithelial
neoplasia (CIN) 3+ over three years was <1 percent [80].

● Reflex cytology (Pap) testing – In reflex cytology testing, when an HPV test is reported as positive,
Pap testing is performed to determine if a patient should be sent for colposcopy. Availability of this
technique using approved testing is limited in some locations, including the United States.

With reflex cytology (Pap) testing, if the HPV testing is normal (thus, Pap testing is not done) and all
prior screening results are normal, screening is suggested again in three to five years, as described
above.

The recommended frequency of testing varies with the chosen test or combination of tests. In modeling
studies of screening at various time intervals, decreasing the frequency of screening is associated with a
decrease in colposcopy rates. In one modeling study of women age >30 years, a combination of Pap and
HPV testing every five years was as effective as screening with Pap testing alone every three years [18].
In another modeling study of women age 40 years, co-testing every five years was associated with
decreased colposcopies compared with co-testing every three years, with only a minimal change in
lifetime cancer risk (0.39 versus 0.61 percent) [81]. However, some argue that the increased risk for
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cancer with less frequent screening is not minimal and that annual Pap testing should be the gold
standard used for comparison in modeling studies [82].

Follow-up results that are not normal — Appropriate follow-up of abnormal tests is essential for
effective cervical cancer screening. Women who have abnormal Pap tests and/or HPV testing need
appropriate follow-up and possibly further subsequent evaluation, depending upon the results.
Recommendations differ depending on the woman's age, test results, and whether or not both Pap and
HPV testing were done.

Inadequate follow-up of abnormal Pap tests performed months or years before the diagnosis of cancer
was found in up to 13 percent of women with invasive cervical cancer [83-86]. In one study, the median
time from the date of the "failed" follow-up for abnormal Pap test to the cancer diagnosis was 22 months;
older age and poverty were associated with greater likelihood of a failed follow-up process [87].

Interpretation of Pap (table 4) and HPV test results is described separately. (See "Cervical and vaginal
cytology: Interpretation of results (Pap test report)" and "Human papillomavirus testing of the cervix:
Management of abnormal results", section on 'Hpv-positive results'.)

Subsequent follow-up for women who have an abnormal Pap test or HPV test is described in detail in the
following topic chapters:

Pap test satisfactory for evaluation but limited – A Pap test may be reported as satisfactory for
evaluation but limited (eg, due to partially obscuring blood or inflammation). Management of a Pap
test that is satisfactory but limited is discussed separately. (See "Cervical and vaginal cytology:
Interpretation of results (Pap test report)", section on 'Satisfactory for evaluation'.)

Pap test unsatisfactory – A Pap test may be reported as unsatisfactory for interpretation. An
unsatisfactory Pap specimen is not reliable for evaluation of epithelial abnormalities. Management of
an unsatisfactory Pap test is discussed separately. (See "Cervical and vaginal cytology:
Interpretation of results (Pap test report)", section on 'Unsatisfactory for evaluation'.)

● Abnormal HPV testing but normal Pap testing – Follow-up for abnormal HPV testing with normal
Pap testing is described separately (algorithm 1) (See "Cervical and vaginal cytology: Interpretation
of results (Pap test report)", section on 'Normal cytology'.)

● Abnormal HPV testing without Pap test – Follow-up for abnormal HPV testing without Pap testing
is described separately [26,74,88]. (See "Human papillomavirus testing of the cervix: Management
of abnormal results", section on 'Hpv-positive results' and "Human papillomavirus testing of the
cervix: Management of abnormal results", section on 'HPV genotyping'.)

● Abnormal Pap results – Follow-up is necessary for a patient who has an abnormal Pap test result.
Depending on the Pap test findings, subsequent testing (eg, colposcopy) may be guided by the
results of HPV testing, if performed with the Pap test, as discussed in the following topics:

• Atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells
(cannot exclude high-grade lesion, ASC-H) (see "Cervical cytology: Evaluation of abnormal
squamous lesions")
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• Atypical and malignant glandular cells (see "Cervical cytology: Evaluation of atypical and
malignant glandular cells")

• Low-grade squamous intraepithelial lesions (LSIL) (see "Cervical cytology: Evaluation of

abnormal squamous lesions")

• High-grade squamous intraepithelial lesions (HSIL) (see "Cervical cytology: Evaluation of

abnormal squamous lesions")

• Cervical intraepithelial neoplasia (CIN) (see "Cervical intraepithelial neoplasia: Management")

• Cervical cancer (see "Invasive cervical cancer: Epidemiology, risk factors, clinical
manifestations, and diagnosis", section on 'Diagnosis')

BENEFITS AND HARMS OF SCREENING

The benefits of cervical cancer screening in decreasing the mortality and incidence of cervical cancer
need to be weighed against the risks of false-positive screening results and overdiagnosis.

Mortality reduction — Systematic reviews and meta-analyses of observational studies provide

consistent and compelling evidence that screening leads to a decrease in mortality due to cervical cancer
(figure 2) [30,68]. Multiple observational studies showed reductions in cervical cancer mortality as
Papanicolaou (Pap) screening was implemented, leading to the adoption of screening programs
[30,71,89-97]. In the United States, mortality due to cervical cancer has continued to decrease since the
1970s (figure 3).

There are no clinical trials comparing mortality rates among the various screening strategies. However, a
microsimulation model for the US Preventive Services Task Force (USPSTF) found that screening
strategies that included human papillomavirus (HPV) testing (ie, primary HPV testing or co-testing [Pap
test with HPV testing]) were associated with fewer cervical cancer deaths compared with screening
strategies that included Pap testing (ie, Pap testing alone every three years or co-testing every five
years). In this model, cervical cancer deaths associated with screening that included Pap testing ranged
from 0.30 to 0.76 deaths per 1000 women versus 0.23 to 0.29 deaths per 1000 women with screening
that included HPV testing [98].

Cervical disease detection and incidence — Systematic reviews, meta-analyses, and observational
studies consistently show that screening is associated with a decreased incidence of cervical cancer
(figure 2) [30,68].

The United States adopted Pap test screening in the 1950s, and by the mid-1980s cervical cancer
incidence decreased by 70 percent [99]. In observational studies, screening is also associated with
higher cure rates for invasive cervical cancer [100,101]. In a meta-analysis of 12 case-control studies,
Pap testing was associated with a decreased risk of invasive cervical cancer (odds ratio [OR] 0.35, 95%
CI 0.30-0.41) [30]. (See "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and
diagnosis", section on 'Incidence and mortality'.)

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Primary HPV testing has been shown in several studies to be a very sensitive test for identifying potential
precursors of cervical cancer during an initial round of screening [68,80,102]. In a systematic review for
the USPSTF, primary HPV screening among women aged 25 to 65 years compared with Pap testing
alone was associated with increased detection of cervical intraepithelial neoplasia (CIN) 3+ in the initial
round of screening (relative risk (RR) range 1.61 [95% CI 1.09-2.37] to 7.46 [95% CI 1.02-54.66]),
whereas co-testing was not associated with initial increased CIN3+ detection compared with Pap testing
alone [103].

A benefit of co-testing on the incidence of cervical cancer has been seen in several studies. In large
cohort studies, women who have negative co-testing have an extremely low risk (<1 percent) of
developing CIN 3 or a higher-risk lesion within the next 5 to 10 years [104-110]. In a large European
meta-analysis, compared with Pap-based testing, screening with HPV testing (largely as co-testing) was
associated with a lower rate of incident cervical cancer at a median of 6.5 years of follow-up (rate ratio
0.60, 95% CI 0.40-0.89) [111]. In this well-screened population, the overall incidence of invasive cervical
cancer was low (107 cervical cancers found among 176,464 women followed for 6.5 years [1.2 million
person-years]).

After the initial round of screening, some studies have found a lower cumulative incidence of CIN 3+
associated with HPV testing, whereas others found that including HPV testing (ie, primary HPV testing or
co-testing) led to earlier detection, but not reduced incidence, of high-grade cervical lesions including
cancer. For example, at 48 months, the large HPV FOCAL Study found a lower incidence of CIN 3+
associated with initial HPV testing (incidence ratio (IR) 2.3/1000 [95% CI 1.5-3.5]) than with initial Pap
testing (IR 5.5/1000 [95% CI 4.2-7.2]; RR 0.42 [95% CI, 0.25-0.69]) [112]. The relative risk of CIN 2+ was
also lower with primary HPV testing than with initial Pap testing. By contrast, in one trial comparing
screening with co-testing or with Pap testing alone (co-testing), initially women who had co-testing had
fewer CIN 3+ lesions; however, over two rounds of screening, overall rates of CIN 3 or a higher-risk
lesion were equivalent in the two groups [102]. Similarly, in the Population-Based Screening Study
Amsterdam, which compared initial testing with either co-testing or with Pap alone, followed by
rescreening at five years with co-testing, those initially screened with co-testing had less CIN 3 or a
higher-risk lesion (88 versus 122 cases, RR 0.73, 95% CI 0.55-0.96) and less cervical cancer (4 versus
14 cancers, RR 0.29, 95% CI 0.10-0.87) [113]. However, the cumulative detection of CIN 3 or a higher-
risk lesion and cervical cancer over the two testing rounds did not differ between the two groups. The
reduction in second-round lesions appeared to be directly attributable to a reduction in HPV 16-positive
lesions.

False-positive and colposcopy rates — Studies have found that primary HPV testing is associated
with an increased number of positive results, although outcomes of these results were uncertain
[23,24,68,75,103]. Some detected abnormalities can lead to unnecessary diagnostic procedures and
treatment, especially because HPV often regresses over time, contributing to the rate of false positives
and thus to unnecessary colposcopies, particularly in younger women.

Both HPV testing and Pap testing are associated with false-positive results that lead to subsequent
testing and follow-up examinations. Screening strategies that include HPV testing have been associated
with more false-positive results than screening with Pap testing alone [103]. In a USPSTF systematic

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review that compared methods that include HPV testing versus Pap testing alone, during first-round
screening, false-positive rates with primary HPV testing were 6.6 to 7.4 percent compared with 2.6 to 6.5
percent for Pap testing alone. In separate studies, false-positive rates with co-testing were 5.8 to 19.9
percent compared with 2.6 to 10.9 percent for Pap testing alone. In one European study in women aged
25 to 60 years, HPV screening increased the detection of CIN 2 and 3; however, many of these lesions
spontaneously regressed, particularly in women aged <30 years [23,24]. (See "Cervical intraepithelial
neoplasia: Management", section on 'CIN 2,3'.)

A consequence of higher rate of positive tests is a higher rate of follow-up examinations including
colposcopy. Higher colposcopy rates have been associated with use of HPV testing rather than Pap
testing alone. In the USPSTF systematic review, the colposcopy rate after primary HPV testing was 1.2
to 7.9 percent compared with 1.1 to 3.1 percent for Pap alone. Among studies that compared co-testing
with Pap testing, the colposcopy rates were 6.8 to 10.9 percent versus 3.3 to 5.2 percent respectively
[103]. Other studies have similarly found that primary HPV testing is associated with an increased
number of colposcopies performed [23,24,68,75,103]. Primary HPV testing with reflex Pap testing has
been associated with a substantial increase in various types of follow-up, including colposcopies [25,80].
For example, in a randomized trial of over 100,000 women, compared with Pap test screening, HPV
testing with reflex Pap testing resulted in 27 percent more colposcopies in women aged 25 to 35 years
as well as increased rates of recommendation for intensified follow-up in women 25 to 29 years (22
versus 10 percent) [25].

Modeling studies have shown variations in colposcopy rates depending upon the screening method
used. In one study, primary HPV testing was associated with increased life-years; however, it was also
associated with more colposcopies compared with no screening, Pap testing, and co-testing [98]. In that
model, switching at age 30 years to HPV testing with cytology triage (reflex Pap testing) every five years
was associated with 73 colposcopies per life-year gained, whereas Pap testing alone every three years
from ages 21 to 65 years was associated with three colposcopies per life-year gained compared with no
screening. Another modeling study predicted that co-testing would result in nearly three times as many
colposcopies as Pap testing, Pap with reflex HPV testing, or HPV testing with reflex Pap testing [81].

Other potential harms — Adverse health outcomes related to cervical cancer screening include the
potential for adverse effects on reproduction, as well as the discomfort, psychosocial consequences, and
costs of procedures used to diagnose and treat cervical abnormalities. The harmful effects of treatment
on fertility (eg, cervical stenosis) and on pregnancy outcomes (eg, increased risk of second-trimester
pregnancy loss, preterm premature rupture of membranes, preterm delivery, and perinatal mortality) are
discussed separately. (See "Reproductive effects of cervical excisional and ablative procedures".)

The discomforts and inconveniences of Pap test screening are apparent. They increase with the
frequency and duration of screening and may be particularly relevant for adolescents and older adults.

Screening also has psychosocial consequences. High levels of anxiety are associated with colposcopy
referral for women with high- or low-grade abnormalities as well as with surveillance for mild test
abnormalities [114-116]. Anxiety is heightened in women with a positive HPV test and in younger women
[115,117].

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The costs of cervical cancer screening include both monetary and opportunity costs. Monetary costs
relate to screening and to procedures that result from screening. Opportunity costs relate to the
possibility of overlooking more immediate health care issues during medical visits in which cervical
cancer screening is discussed and performed.

IMPROVING SCREENING RATES

More than one-half of women who develop cervical cancer have not been screened appropriately
[83,118-120]. Furthermore, among women diagnosed with invasive cervical carcinoma, one-half have
never had a Papanicolaou (Pap) test; another 10 percent have not had a test in the past five years [118].
In a survey of screening in the United States in 2015, 83 percent of women aged 21 to 65 years with a
cervix reported having had a Pap test within the preceding three years or co-testing within five years.
[121].

In United States surveillance, never-screened and under-screened women tend to be older women and
those with no usual source of health care, the uninsured, and women who immigrated to the United
States within the past 10 years [122-124]. In Canada, screening rates are low in women with disability
and those with chronic conditions [125].

Various strategies can be used to increase screening rates. Actively inviting women to schedule an
appointment for cervical cancer screening is an effective way to increase participation in a screening
program [126], though even active solicitation resulted in less than a 20 percent increase in screening in
one systematic review [127]. The most effective single intervention used a dedicated nurse practitioner
and offered same-day screening (33 percent increase in screening).

Urgent care clinic visits can be used as an opportunity to screen women who are unlikely to otherwise
comply with cervical cancer screening recommendations [128]. However, patient follow-up in this setting
can be more difficult than in the longitudinal care setting.

Initiating a reminder system is helpful for ensuring compliance with follow-up [129,130]. A systematic
review of 38 randomized trials of interventions to promote screening for cervical cancer found good
evidence that invitation letters can increase cancer screening uptake, and more limited evidence that
educational interventions are also effective [131].

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

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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.)

● Basics topic (see "Patient education: Pap tests (The Basics)")

● Beyond the Basics topics (see "Patient education: Cervical cancer screening (Beyond the Basics)"
and "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

● There is consistent and compelling evidence that screening leads to a decrease in mortality due to
cervical cancer. (See 'Benefits and harms of screening' above.)

● For women age ≥21 years, we recommend cervical cancer screening (Grade 1A).

• We suggest not screening asymptomatic immunocompetent women younger than age 21 years.
(See 'Age less than 21 years' above.)

• For average-risk women who are asymptomatic and immunocompetent, we initiate screening at
age 21 years. Some experts and guideline groups recommend initiating screening at different
ages (usually between 20 and 25 years). (See 'Age 21 to less than 30 years' above.)

● For higher-risk patients (eg, those with prior abnormal screening results or with
immunosuppression), recommendations for what ages to start and discontinue screening and which
screening strategy to choose may differ. Recommendations may also differ in different patient
populations or different settings. (See 'Screening in higher-risk women' above and 'Screening in
other populations' above and "Screening for cervical cancer in resource-limited settings".)

● Symptomatic women should have Papanicolaou (Pap) testing as part of a diagnostic workup,
regardless of prior screening results. (See 'Symptomatic women' above.)

● The age at which we discontinue screening takes into account whether the patient had adequate
prior screening and whether she had prior abnormal results and includes informed discussions of the
potential benefits and harms of screening. For older women, continuing screening is contingent on a
life expectancy >10 years. (See 'When to discontinue screening' above.)

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• For women who have had adequate prior screening with normal results and no cervical cancer
risk factors, the optimal age to discontinue screening is uncertain. We screen through at least
age 65 years. While data are limited and potential harms of screening need to be considered
(eg, false positives), some UpToDate authors and editors continue to offer screening through
age 74 years. (See 'If adequate prior screening' above.)

• For women who have had adequate prior screening but have a history of abnormal results, are
immunosuppressed, or would like to continue screening, some contributors continue screening
up to about age 80 years, whereas others stop screening earlier depending on the risk factor
and the patient’s life expectancy. (See 'Other higher-risk patients' above and 'Screening in
higher-risk women' above.)

• For women older than age 65 years with inadequate prior screening, we suggest screening with
co-testing annually for three years before spreading out the interval to every five years. (See 'If
prior screening inadequate or unknown' above.)

● Screening strategies (choice of test or combination of tests) for cervical cancer include Pap testing
alone; primary human papillomavirus (HPV) testing alone; and different combinations or sequences
of Pap and HPV testing. The frequency of testing depends on the test(s) chosen and the patient’s
prior screening history. (See 'Screening methods' above.)

● Recommendations regarding the choice of screening strategy differ for younger versus older
women, available resources, and other risk factors, and the patient should be included in the
decision about which approach to use, depending on what’s available in that setting. (See 'Age 21 to
less than 30 years' above and 'Age 30 years or older' above and 'Screening in higher-risk women'
above and 'Screening in other populations' above.)

• For average-risk women age 21 to <30 years, we suggest Pap testing alone every three years.
Some clinicians suggest Pap testing with reflex to HPV testing every three years. (See 'Age 21
to less than 30 years' above and 'Benefits and harms of screening' above.)

• For average-risk women age ≥30 years who are immunocompetent and whose prior screening
results (if any) are all normal, we suggest screening with one of the following strategies, and at
the frequency shown, as long as all results are normal: co-testing (Pap test and HPV testing)
every five years, primary HPV testing every five years. Pap test with reflex HPV testing every
three years, or Pap test alone every three years. (See 'Age 30 years or older' above.)

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

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GRAPHICS

Percent of new cases by age group: Cervix uteri cancer*

Infection of the cervix with human papillomavirus (HPV) is the most common cause of
cervical cancer, although not all women with HPV infection will develop cervical cancer. The
number of new cases of cervix uteri cancer was 7.8 per 100,000 women per year based on
2007 to 2011 cases. Cervix uteri cancer is most frequently diagnosed among women aged
35 to 44. Median age at diagnosis is 49.

* SEER 18 2007 to 2011, all races, females.

Reproduced from: SEER Cancer Statistics Factsheets: Cervix Uteri Cancer. National Cancer
Institute. Bethesda, MD. Available at: http://seer.cancer.gov/statfacts/html/cervix.html
(Accessed on December 8, 2014).

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Cervical cancer screening recommendations from United States professional

organizations*

Recommended screening
test Post-
Age to Age to
and frequency hysterectomy HPV
Organization initiate discontinue
for benign vaccination
(years) (years) Age 21 to
Age ≥30
29 disease
years
years

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

(2012) every 3 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 testing every 3
every 3 years years
for women
age ≥25

USPSTF (2018) 21 65 § Pap test One of these Not indicated ¥ Same

every 3 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 years
for Can
women consider
age primary
≥25 HPV testing
every 3
years for
women age
≥25
§ ¥
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§
ACP (2015) 21 65 Pap test One of these Not indicated ¥ N/A
every 3 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; hrHPV: high-risk human papillomavirus; ACOG: American College of Obstetricians and Gynecologists; ACP: American
College of Physicians; 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.

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Normal pap smear

Reproduced with permission from Douglas K. Hanks, MD.

Graphic 55957 Version 2.0

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Abnormal pap smear

(A) Atypical squamous cells of undetermined significance (ASCUS).

(B) Low-grade squamous intraepithelial lesion (LSIL).
(C) High-grade squamous intraepithelial lesion (HSIL).

Reproduced with permission from Douglas K. Hanks, MD.

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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 (Accessed on June 11, 2012).

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Human papillomavirus (HPV) tests

Number of HPV
Test HPV types identified Results*
identified

Hybrid Capture 2 13 16, 18, 31, 33, 35, 39, 45, 51, 52, Pooled result
56, 58, 59, 68 (not 66)

Cervista HPV HR test ¶ 14 16, 18, 31, 33, 35, 39, 45, 51, 52, Pooled result
56, 58, 59, 66, 68

cobas HPV test Δ 14 16, 18 Specific for 16/18

31, 33, 35, 39, 45, 51, 52, 56, 58, Pooled result for other 12 subtypes
59, 66, 68

Aptima mRNA test ◊ 14 16, 18, 31, 33, 35, 39, 45, 51, 52, Pooled result
56, 58, 59, 66, 68

HPV: human papillomavirus; FDA: US Food and Drug Administration.

* Pooled result: Positive result for any of the HPV types, not specific for any one type.
¶ The Cervista 16/18 specifically detects HPV 16 and 18. It is FDA-approved for use in women ≥30 years as a follow-up to a
positive Cervista HPV HR test or in women any age with borderline cytology results.
Δ FDA-approved for use alone as primary screening in women 25 years and older.
◊ The Aptima HPV 16 18/45 specifically detects HPV 16, 18, and/or 45. It is FDA-approved for use in women ≥30 years as a
follow-up to a positive Aptima mRNA test or in women ≥21 years as a follow-up to a borderline cytology result.

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Bethesda 2014 classification system for cervical cytology

Specimen type
Indicate conventional smear (Pap smear), liquid-based preparation (Pap test), versus other

Specimen adequacy

Satisfactory for evaluation (describe presence or absence of endocervical/transformation zone component and any
other quality indicators, eg, partially obscuring blood, inflammation, etc)
Unsatisfactory for evaluation (specify reason)
Specimen rejected/not processed (specify reason)
Specimen processed and examined, but unsatisfactory for evaluation of epithelial abnormality because of (specify
reason)

General categorization (optional)

Negative for intraepithelial lesion or malignancy

Other: see "Interpretation/results" (eg, endometrial cells in a woman older than 45 years)
Epithelial cell abnormality: see "Interpretation/results" (specify "squamous" or "glandular," as appropriate)

Interpretation/results
Negative for intraepithelial lesion or malignancy

(When there is no cellular evidence of neoplasia, state this in the "General categorization" above and/or in the
"Interpretation/results" section of the report—whether there are organisms or other non-neoplastic findings)

Non-neoplastic findings (optional to report)

Non-neoplastic cellular variations:

Squamous metaplasia
Keratotic changes
Tubal metaplasia
Atrophy
Pregnancy-associated changes
Reactive cellular changes associated with:
Inflammation (includes typical repair)
Lymphocytic (follicular) cervicitis
Radiation
Intrauterine contraceptive device (IUD)
Glandular cells status posthysterectomy

Organisms

Trichomonas vaginalis
Fungal organisms morphologically consistent with Candida spp
Shift in flora suggestive of bacterial vaginosis
Bacteria morphologically consistent with Actinomyces spp
Cellular changes consistent with herpes simplex virus
Cellular changes consistent with cytomegalovirus

Other

Endometrial cells (in a woman older than 45 years)

(also specify if "negative for squamous intraepithelial lesion")

Epithelial cell abnormalities

Squamous cell
Atypical squamous cells
Of undetermined significance (ASC-US)
Cannot exclude HSIL (ASC-H)
Low-grade squamous intraepithelial lesion (LSIL)
(encompassing: HPV/mild dysplasia/CIN-1)
High-grade squamous intraepithelial lesion (HSIL)
(encompassing: moderate and severe dysplasia, CIS; CIN-2 and CIN-3)
With features suspicious for invasion (if invasion is suspected)
Squamous cell carcinoma
Glandular cell

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Atypical
Endocervical cells (NOS or specify in comments)
Endometrial cells (NOS or specify in comments)
Glandular cells (NOS or specify in comments)
Atypical
Endocervical cells, favor neoplastic
Glandular cells, favor neoplastic
Endocervical adenocarcinoma in situ
Adenocarcinoma
Endocervical
Endometrial
Extrauterine
Not otherwise specified (NOS)

Other malignant neoplasms (specify)

Adjunctive testing
Provide a brief description of the test method(s) and report the result so that it is easily understood by the clinician

Computer-assisted interpretation of cervical cytology

If case examined by an automated device, specify the device and result

Educational notes and comments appended to cytology reports (optional)

Suggestions should be concise and consistent with clinical follow-up guidelines published by professional organizations
(references to relevant publications may be included)

Pap: Papanicolaou; HPV: human papillomavirus; CIN: cervical intraepithelial neoplasia; CIS: carcinoma in situ.

From: Nayar R, Wilbur DC. The Pap Test and Bethesda 2014: "The reports of my demise have been greatly exaggerated. (after a
quotation from Mark Twain)". J Low Genit Tract Dis 2015; 19:175. DOI: 10.1097/LGT.0000000000000115. Copyright © 2015
American Society for Colposcopy and Cervical Pathology, The International Society for the Study of Vulvovaginal Disease, and The
International Federation of Cervical Pathology and Colposcopy. Reproduced with permission from Lippincott Williams & Wilkins.
Unauthorized reproduction of this material is prohibited.

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Management of Women ≥ Age 30, who are Cytology Negative, but HPV Positive

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.

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A multiple time-series study

Change in cervical cancer mortality rates according to year organized Pap smear screening programs
were implemented and targeted coverage. Arrows mark the year coverage was achieved for each
country.

Reproduced from: Laara E, Day NE, Hakama M. Trends in mortality from cervical cancer in Nordic countries:
association with organized screening programmes. Lancet 1987;1(8544):1247. Illustration used with the
permission of Elsevier Inc. All rights reserved.

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New cases, deaths, and 5-year relative survival

SEER 9 incidence and United States mortality from 1975 to 2011; all races; females. Rates are age-adjusted.

Reproduced from: SEER Cancer Statistics Factsheets: Cervix Uteri Cancer. National Cancer Institute. Bethesda,
MD. Available at: http://seer.cancer.gov/statfacts/html/cervix.html (Accessed on November 13, 2014).

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Contributor Disclosures
Sarah Feldman, MD, MPH Nothing to disclose Annekathryn Goodman, MD, MPH, MS Nothing to
disclose Jeffrey F Peipert, MD, PhD Grant/Research/Clinical Trial Support: CooperSurgical [Contraception]; Bayer
[Contraception]; Merck [Contraception]. Consultant/Advisory Boards: CooperSurgical [Contraception]; Bayer
[Contraception]. Barbara Goff, MD Employment (Spouse): Lilly [General oncology] - No relevant conflict on
topics. Joann G Elmore, MD, MPH Nothing to disclose Lisa Kunins, MD Nothing to disclose Alana Chakrabarti,
MD 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

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