Screening for cervical cancer

Authors
Sarah Feldman, MD, MPH
Annekathryn Goodman, MD
Jeffrey F Peipert, MD, PhD
Section Editors
Barbara Goff, MD
Joann G Elmore, MD, MPH
Deputy Editor
Lee Park, MD, MPH
Disclosures: Sarah Feldman, MD, MPH Nothing to disclose. Annekathryn Goodman, MD Nothing to
disclose. Jeffrey F Peipert, MD, PhD Nothing to disclose. Barbara Goff, MD Nothing to disclose. Joann G Elmore,
MD, MPH Grant/Research Support: NIH Robert Wood Johnson Foundation [research]. Consultant/Advisory Boards:
Non-profit Informed Medical Decisions Foundation/Healthwise [Patient Decision Aids]. Other Financial Interest:
Elsevier, Inc [Royalties from textbook]. Lee Park, MD, MPH Employment (Spouse): Novartis [Age-related macular
degeneration (ranibizumab)].
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

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jun 2015. | This topic last updated: Jun 03, 2015.
INTRODUCTION Cervical cancer screening has decreased the incidence of and mortality from
cervical cancer. Methods for screening include evaluation with the Papanicolaou (Pap) test
(cytology) and testing for high-risk types of human papilloma virus (HPV). This discussion will focus
on recommendations for screening in developed countries, including appropriate ages for the
initiation and discontinuation, frequency, and screening methods.
Techniques for performing screening tests, interpretation of tests, management of abnormalities,
and screening women who are HIV positive are discussed separately, as is cervical cancer
screening in resource-limited countries.
(See "Cervical cancer screening tests: Techniques for cervical cytology and human
papillomavirus testing".)
(See "Cervical and vaginal cytology: Interpretation of results".)
(See "Cervical cytology: Evaluation of atypical and malignant glandular cells".)
(See "Cervical cytology: Evaluation of atypical squamous cells (ASC-US and ASC-H)".)
(See "Cervical cytology: Evaluation of low-grade squamous intraepithelial lesions (LSIL)".)
(See "Cervical intraepithelial neoplasia: Management of low-grade and high-grade lesions".)
(See "Screening for cervical cancer in HIV-infected women".)
(See "Screening for cervical cancer in resource-limited settings".)
BACKGROUND There are two main types of cervical cancer: squamous cell carcinoma and
adenocarcinoma. Squamous cell carcinoma of the cervix is more prevalent than adenocarcinoma.
Screening can detect precursors and early-stage disease for both types. Treatment of precursors
and early-stage disease can prevent the development of invasive cervical cancer.

Cervical cancer screening started with the 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 human papillomavirus (HPV), which are central to
the pathogenesis of cervical cancer. (See "Cervical intraepithelial neoplasia: Terminology, incidence,
pathogenesis, and prevention", section on 'Role of human papillomavirus'.)
While it is clear that cervical cancer screening decreases the incidence and mortality of cervical
cancer, whom to screen, the optimal testing method (Pap test, HPV testing, or both) and frequency
are debated. The benefits and harms of cervical cancer screening vary with age, medical history,
and risk factors (eg, non-adherence to screening).
EPIDEMIOLOGY AND RISK FACTORS Cervical cancer is common among women worldwide.
The incidence and mortality rates are related to the presence of screening and HPV vaccination
programs. Most cases of cervical cancer occur in developing countries [1]. In the United States,
cervical cancer and cervical cancer mortality are rare in young women (20 years) (figure
1 and figure 2). (See "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations,
and diagnosis".)
HPV Infection with high-risk strains of HPV and persistence of HPV infection are the most
important determinants of progression to cervical cancer [2-6]. Most risk factors for cervical
cancer are associated with factors that increase the risk of acquiring HPV infection (eg, early
onset of sexual activity, multiple or high-risk sexual partners) or impaired ability to clear HPV
infection (eg, immunosuppression) [7]. (See "Invasive cervical cancer: Epidemiology, risk
factors, clinical manifestations, and diagnosis", section on 'Risk factors' and "Invasive cervical
adenocarcinoma", section on 'Epidemiology and risk factors'.)
Of the approximately 30 to 40 HPV genotypes that infect the genital tract mucosa, types 16
and 18 are responsible for about 70 percent of cervical cancer and 50 percent of cervical
cancer precursors [8]. Other oncogenic types (table 1) of HPV are less commonly associated
with cervical cancer and cervical cancer precursors. (See "Invasive cervical cancer:
Epidemiology, risk factors, clinical manifestations, and diagnosis", section on
'Pathogenesis' and "Epidemiology of human papillomavirus infections", section on 'Cervical
cancer'.)
There is a high prevalence of HPV infection in sexually active women, particularly in younger
women. Most young women will clear the HPV infection within 8 to 24 months [9]. The
prevalence of cervical HPV infection decreases after the age of 30, but the likelihood of
persistent infection increases. The epidemiology and prevalence of HPV infection may also
vary geographically. (See "Epidemiology of human papillomavirus infections", section on
'Epidemiology in females'.)
Nonadherence to screening More than one-half of women who develop cervical cancer
have not been screened appropriately [10-13]. Furthermore, among women diagnosed with
invasive cervical carcinoma, one-half have never had a Pap test; another 10 percent have not
had a test in the past five years [10]. In United States surveillance, never-screened and underscreened women tend to be those with no usual source of health care, the uninsured, and
women who immigrated to the United States within the past 10 years [14-16]. In Canada,
screening rates are low in women with disability and those with chronic conditions [17].
(See'Improving screening rates' below.)

Other risk factors Other risk factors associated with cervical cancer include oral
contraceptive use and cigarette smoking (for squamous cell cancer but not adenocarcinoma).
(See "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and
diagnosis", section on 'Risk factors' and "Invasive cervical adenocarcinoma", section on
'Epidemiology and risk factors'.)
BENEFITS OF SCREENING Cervical cancer screening detects precancerous lesions and earlystage disease, the treatment of which decreases the incidence of cervical cancer and cervical
cancer mortality, respectively. While cytologic screening for cervical cancer with Papanicolaou (Pap)
test has never been evaluated in a randomized trial, multiple observational studies in various
countries have shown reductions in cervical cancer incidence and mortality as screening is
implemented [18-27]. This has led to the adoption of screening programs in all developed and many
developing nations worldwide.
Systematic reviews and meta-analyses of observational studies provide consistent and compelling
evidence that screening leads to a decrease in incidence and mortality from cervical cancer (figure
3) [28,29]. In a meta-analysis of 12 case-control studies, cytology screening was associated with
decreased risk of invasive cervical cancer (odds ratio 0.35, 95% CI 0.30-0.41) [28].
The United States adopted screening with the Pap test in the 1950s and by the mid-1980s cervical
cancer incidence decreased by 70 percent [30]. Cervical cancer incidence and mortality in the
United States has continued to decrease since the 1970s (figure 4). Furthermore, in observational
studies, screening is associated with higher cure rates and decreased risk for invasive cervical
cancer [31,32]. (See "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations,
and diagnosis", section on 'Incidence and mortality'.)
HARMS OF SCREENING The benefits of screening in decreasing the incidence and mortality of
cervical cancer need to be weighed against the risks of overdiagnosis. Screening with Pap
test and/or HPV testing may detect abnormalities that would clear without intervention and this can
lead to unnecessary diagnostic procedures and treatment. Particularly in young women, infection
with human papillomavirus (HPV) may be transient and cervical dysplasia may regress
spontaneously. (See 'Initial screening' below.)
The most consequential adverse health outcomes related to cervical cancer screening arise from
the downstream consequences of procedures used to diagnose and treat cervical abnormalities.
The reproductive effects of treatment, which may include cervical stenosis, increased risk of second
trimester pregnancy loss, preterm premature rupture of membranes, preterm delivery, and perinatal
mortality, are discussed elsewhere. (See "Cervical intraepithelial neoplasia: Reproductive effects of
treatment".)
Other adverse effects of screening include discomfort, psychosocial consequences, and costs. The
discomfort and inconvenience of Pap test screening are apparent, although not easily measurable.
Both increase with the frequency and duration of screening, and may be particularly relevant for
adolescents and older adults.
A number of studies have examined the psychosocial consequences of screening. High levels of
anxiety are associated with colposcopy referral for women with both high-grade and low-grade
abnormalities, and with surveillance for mild test abnormalities [33-35]. Anxiety is heightened in
women with a positive HPV test and in younger women [34,36].

The costs of cervical cancer screening include both monetary and opportunity costs. Monetary
costs relate to procedures that result from screening. Opportunity costs relate to overlooking
potentially more important health care issues during medical visits in which cervical cancer
screening is discussed and performed.
ROUTINE SCREENING RECOMMENDATIONS The screening recommendations in this section
generally apply to immune competent women who have an intact cervix.
Women in specific populations (eg, immunocompromised, status post total hysterectomy, in utero
diethylstilbestrol exposure) may have different screening recommendations. (See 'Special
populations' below.)
Initial screening In the United States, we recommend that cervical cancer screening be initiated
no earlier than age 21 in immunocompetent, asymptomatic women. In such women, we suggest
initiating screening at age 21, regardless of the age of initiation of sexual activity [37]. Other
countries may initiate screening at different ages (usually between 20 and 25 years) [38].
Observational studies suggest that the potential benefits of adolescent screening are offset by
potential harms, weighing against aggressive screening in this age group [39]. Screening in
immunocompromised women and diagnostic testing in symptomatic women younger than 21 years
are discussed elsewhere. (See'Immunocompromised women' below and "Invasive cervical cancer:
Epidemiology, risk factors, clinical manifestations, and diagnosis".)
In the United States, the age-adjusted incidence of cervical cancer in women ages 15 to 19 years is
0.1 per 100,000 [40]. Adolescents are also more likely to spontaneously clear HPV infection and
associated abnormalities. While rates of atypical squamous cells of undetermined significant (ASCUS) 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 [41-45]. Furthermore, diagnostic and therapeutic
procedures for abnormalities may result in more harm in younger women. (See"Cervical cytology:
Evaluation of atypical squamous cells (ASC-US and ASC-H)", section on 'Women ages 21 to
24' and "Cervical intraepithelial neoplasia: Reproductive effects of treatment".)
Starting at age 21, 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, as well as reluctance to acknowledge prior sexual abuse or rape. In particular, women who
have been sexually abused or raped are often reluctant to acknowledge this history, and abuse may
underlie the decision to not engage in subsequent sexual activity.
Guidelines in the United States recommend delaying screening until age 21 (table 2) [6,46,47].
International guidelines vary. European guidelines are available from theEuropean Cervical Cancer
Association.
Women <30 years We suggest screening women age <30 years with Pap test alone at intervals
of every three years. (See 'The Papanicolaou test' below.)
We suggest that women age <30 years not be screened with HPV testing (primary or co-testing)
[37]. In such women, who are more likely to have transient HPV infections, the poor specificity and
correspondingly poor positive predictive value limit the usefulness of HPV testing as a screening
modality [47]. 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
[48-50]. As an example, in a randomized trial of over 100,000 women, compared with Pap test
screening, primary HPV testing with reflex cytology resulted in 27 percent more colposcopies in
women aged 25 to 35 years and increased rates of recommendation for intensified follow-up in
women 25 to 29 years (22 versus 10 percent) [50]. (See'Primary HPV testing' below and 'Co-testing
(Pap test and HPV testing)' below.)
Guideline-issuing organizations in the United States recommend various screening strategies for
women <30 years (table 2) [6,46,47]. International guidelines vary. European guidelines are
available from the European Cervical Cancer Association.
Women 30 years We suggest women age 30 years and older be screened with either:
Pap test every three years (see 'The Papanicolaou test' below)
Co-testing (Pap test and HPV testing) every five years if both initial tests are negative
(see 'Co-testing (Pap test and HPV testing)' below)
HPV infection in women 30 years is more likely to be persistent and, therefore, has a greater
likelihood of clinical significance [51]. However, any strategy that includes HPV screening (with or
without Pap tests, or with Pap test as triage) increases the number of positive results from
screening and the number of colposcopies performed; long-term outcomes remain uncertain.
(See 'Compared with Pap test' below.)
A 2011 systematic review of HPV screening concluded that although primary HPV testing for
women over age 30 detected more cases of CIN 3 or cancer than cytology, the evidence was
insufficient to determine the net benefit of HPV testing strategies [29]. The authors concluded that
primary HPV testing was "very promising" as a screening strategy, particularly when coupled with
cytology triage prior to colposcopy, but that more data are needed to determine the balance of
benefits and harms from an HPV strategy, including the potential for overdiagnosis and excess
colposcopy. (See 'Primary HPV testing' below.)
Guideline-issuing organizations in the United States recommend screening women 30 years every
three or five years depending on method (table 2) [6,46,47]. International guidelines vary. European
guidelines are available from the European Cervical Cancer Association.
Discontinuing screening The age to discontinue screening in older women depends on
whether or not they have received adequate prior screening.
Adequate prior screening In general, we suggest not screening women aged 65 years and
older provided they meet the following criteria:
No increased risk (ie, history of abnormal screening, current smoker or history of smoking,
unknown screening history, previous HPV-related disease, new partners,
immunocompromised, in utero diethylstilbestrol exposure)
Adequate prior screening: two negative consecutive co-tests or three negative Pap tests
within the past 10 years, with the most recent test within the previous five years [46]
No history of high-grade dysplasia or worse
For women 65 years and older who have undergone adequate prior screening, the harms of
screening may outweigh the benefits [52,53]. Older women are less likely to realize the benefits of

screening because of competing causes of death. The incidence of CIN and carcinoma in situ
peaks in the mid-reproductive years and begins to decline in the fourth decade of life [54]. Cervical
cancer is no more aggressive in older women, and high-grade lesions are rare among older women
who have been previously screened [55].
Pap test abnormalities among previously screened older women may have poor positive predictive
value for significant pathology [56]. A study in pre- and 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 pre-menopausal women, compared with 6 percent of postmenopausal
women [57]. Also, follow-up procedures after an abnormal Pap test are not negligible among older
women. In an observational study of women 65 years, 4 percent who underwent screening Pap
test had a follow-up evaluation, including repeat Pap testing, colposcopy, or surgical procedure (eg,
cryocauterization, laser therapy, conization) [56]. However, among women undergoing follow-up
Pap tests (defined by having a Pap test in the nine months preceding the index Pap test and no
history of gynecologic cancer), 30 percent had at least one downstream intervention.
Guideline-issuing organizations in the United States recommend discontinuing screening at age 65
(table 2). International guidelines vary. European guidelines are available from the European
Cervical Cancer Association.
Women with other risk factors Even in older women who have been adequately
screened, it may be reasonable to continue to screen those with good life expectancy who
have risk factors for cervical cancer. Risk factors include a history of an abnormal Pap test,
current smoker or history of smoking, previous HPV-related disease, or new partners.
Potential screening benefits need to be balanced against the potential harms of cervical
cancer screening in older women. We continue to offer screening to women with good life
expectancy who have risk factors for cervical cancer until about age 80, but the upper age limit
may vary with the risk factor (eg, women with good life expectancy and a history of CIN 2 or
greater should be screened for at least 20 years following diagnosis). (See 'Harms of
screening' above and "Cervical intraepithelial neoplasia: Treatment and follow-up", section on
'Subsequent screening'.)
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 [28]. A subsequent observational study found that when corrected for the high
prevalence of hysterectomy in the United States, the incidence of invasive cervical cancer in
older women may be higher than previously thought, and may not decline with increasing age
[58]. However, data regarding adequacy of cervical cancer screening was not available.
Additional observational studies suggest that continued screening in older women may be
efficacious [59-61].
Inadequate prior screening Older women who have never been screened or who have been
under-screened (no screening within the last 5 years) should undergo screening. We suggest
screening with either Pap test every two to three years or co-testing every five years. The US
Preventive Services Task Force (USPSTF) suggests that screening be continued until age 70 or 75
[47]. (See 'The Papanicolaou test' below and 'Co-testing (Pap test and HPV testing)' below.)
Older women who have never been screened have the highest incidence of and mortality from
cervical cancer and benefit the most from screening [62-64]. Modeling studies suggest that

screening older women who have never been screened could reduce mortality by 74 percent [51].
(See 'Epidemiology and risk factors' above.)
SPECIAL POPULATIONS
Immunocompromised women
Women with HIV Women who are infected with HIV are more likely to have persistent HPV
infection, increased rates of high-grade cervical dysplasia, and are at increased risk for the
development of cervical cancer [65-67]. (See "Screening for cervical cancer in HIV-infected
women".)
Immunosuppressed women Women without HIV but who are on long-term
immunosuppressive therapy (eg, for systemic disease or organ transplants) also have
decreased rates of clearance of HPV infection and the increased rates of cervical dysplasia
and cancer [68]. For women who are immunocompromised from causes other than HIV,
ACOG suggests initiating annual Pap test screening at age 21 [6]. We initiate screening one
year after the onset of sexual activity and screen yearly with Pap test and human papilloma
virus testing.
Most of the information about cervical cancer screening in immunosuppressed women is
related to women with systemic lupus erythematosus (SLE). Rates of abnormal Pap tests,
high-grade dysplasia, and persistence of high-risk HPV subtypes are significantly higher in
women with SLE 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 [7,69-72].
Prior hysterectomy Recommendations for women who have had a hysterectomy depend upon
the type (total or subtotal) and indication (for cervical cancer or other indications). Women who are
uncertain if their cervix was removed at the time of hysterectomy should undergo a pelvic exam to
determine the ongoing need for cervical cancer screening.
Total hysterectomy (with cervix removed) for indications other than cervical cancer or
cervical intraepithelial neoplasia (CIN) We recommend that women who have undergone
total hysterectomy for indications unrelated to cervical cancer or cancer
precursors not undergo screening for cervical cancer.
Women who have undergone a hysterectomy in which the cervix was removed are at a
vanishingly small risk of cervical cancer [73]. Although it was once believed that women
without a uterus were at increased risk for vaginal cancer [74-78], studies show no association
between total hysterectomy for benign disease and subsequent vaginal carcinoma [78-83].
Subtotal hysterectomy (cervix intact) Women who have undergone subtotal
hysterectomy likely share the same risk of cervical cancer as women with an intact uterus and
cervix and screening recommendations are the same. (See 'Routine screening
recommendations' above.)
Hysterectomy for cervical cancer (CIN) Screening in women who have undergone
hysterectomy for CIN 2 or CIN 3 is discussed elsewhere. (See "Cervical intraepithelial
neoplasia: Treatment and follow-up", section on 'Post-hysterectomy'.)

Hysterectomy in women with HIV The role of screening in women with HIV infection who
have had a hysterectomy is discussed elsewhere. (See "Screening for cervical cancer in HIVinfected women", section on 'Screening after hysterectomy'.)
History of CIN 2, CIN 3, or adenocarcinoma in situ Subsequent surveillance and follow-up for
women who have a history of CIN 2, CIN 3, or adenocarcinoma in situ is discussed elsewhere.
(See "Cervical intraepithelial neoplasia: Treatment and follow-up", section on 'Follow-up after
treatment' and "Cervical adenocarcinoma in situ", section on 'Post-hysterectomy followup' and "Cervical adenocarcinoma in situ", section on 'Post-conization follow-up'.)
Diethylstilbestrol exposed women Daughters of women who took 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 'DES
daughters'.)
Women who took diethylstilbestrol (DES) during pregnancy should be screened for cervical cancer
in the same manner as the average-risk general population. While at increased risk for breast
cancer, these women have no increased risk for cervical, vaginal, or other cancers [84].
(See 'Routine screening recommendations' above and"Outcome and follow-up of diethylstilbestrol
(DES) exposed individuals", section on 'DES mothers'.)
Recipients of the HPV vaccine The optimal approach to cervical cancer screening in women
who have received HPV vaccine remains uncertain. HPV vaccination of female adolescents is
anticipated to have a significant impact on the risks for cervical abnormalities [85]. Until data from
clinical trials are available, standard screening recommendations should be observed
[6,8,46,47,86]. The vaccine does not provide immunity against all HPV types responsible for
cervical cancers, and some vaccine recipients may have already been infected with high-risk HPV
[8]. (See 'Routine screening recommendations' above and "Recommendations for the use of human
papillomavirus vaccines".)
Symptomatic women Women 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 screening history. By definition, this diagnostic
evaluation is not "screening," and may require additional follow-up evaluation. (See "Invasive
cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis".)
SCREENING METHODS The available methods for screening are the Pap test and human
papillomavirus (HPV) testing; 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 Papanicolaou test The Papanicolaou (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 ectoand endocervix, where cervical dysplasia and cancers arise. In a systematic review, sensitivity and
specificity varied significantly [87]. There is considerable interobserver variability in test
interpretation, although variability decreases for tests with more severe abnormalities [88].

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".)
The diagnosis of cervical intraepithelial neoplasia or cervical carcinoma requires a biopsy for
histology (figure 5). (See "Cervical intraepithelial neoplasia: Terminology, incidence, pathogenesis,
and prevention".)
The Pap test is more sensitive for detecting squamous malignancy than adenocarcinoma and
adenocarcinoma in situ [26,89]. 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].
Conventional Pap test The conventional Pap test consists of cells, sampled from the
cervix and vagina using a brush or spatula, which are placed directly on a slide and fixed with
a chemical fixative in the office or clinic. With conventional tests, specimens for HPV testing
are collected separately.
Liquid-based Pap test Liquid-based (or thin layer) cytology consists of cells that are
sampled similarly, but then suspended in a liquid transport medium, to be subsequently spun
or filtered in the laboratory and plated as thin layers on slides. HPV testing can be performed
on this specimen.
Systematic reviews of randomized trials comparing liquid-based and conventional Pap tests have
not found better specimen adequacy or improved detection of cancer precursors with liquid-based
tests [29,90,91]. However, liquid-based cytology may increase the yield of adequate specimens in
subgroups of patients, such as those with obscuring blood and inflammation [92].
Frequency of testing When the Pap test is used as the screening method, we suggest
screening every three years. Compared with triennial screening, annual screening only marginally
increases the detection of cervical cancer but doubles or triples the number of downstream
interventions, including colposcopies [93]. The rate of detection of high-grade cytologic
abnormalities is similar with annual or triennial screening [52].
Modeling studies have suggested cancer detection rates to be similar with annual or triennial
screening [93-95]. 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 0.03, 0.05, and 0.05 per 1000 women with
screening annually, every two years, and every three years, respectively [46].
HPV testing HPV tests identify most, but not all, of the high-risk HPV types (table 1). Four HPV
tests are approved by the US Food and Drug Administration (FDA) for use in co-testing with a Pap
test (table 3) [96]. Within this topic review, "HPV testing" refers to any of the approved tests. Other
HPV tests may be used by individual laboratories, but are not approved by the FDA and have not
been validated adequately.
Compared with Pap test HPV testing, either alone or in combination with cervical cytology, is
more sensitive than cervical cytology alone in detecting cervical histopathology, including
adenocarcinoma [29,48,97-104]. Randomized trials have demonstrated a decrease in the overall

incidence of cancer with HPV testing, although a mortality benefit has not been demonstrated
[48,105]. Strategies that include HPV testing increase the number of positive results and
colposcopies performed and long-term outcomes are uncertain [48,49,106]. As examples:
One randomized trial in over 94,000 women assessed the efficacy of HPV screening versus
cytology in reducing the incidence of high-grade lesions and invasive cancer in women aged
25 to 60 years [48]. Although strategies shifted across the two phases of the trial, initial
screening for HPV (with or without cytology) reduced the occurrence of invasive cervical
cancer at a second round of screening (zero cases among patients who were assigned to
HPV screening versus nine in the group without HPV testing). HPV screening increased
detection of high-grade lesions (cervical intraepithelial neoplasia [CIN] 2 and 3 [RR 1.64, 95%
CI 1.18-2.24 for all women, and RR 2.78, 1.96-3.92 for women aged 25 to 34]) over two
rounds of screening. Many of these precancerous lesions spontaneously regress, particularly
in women <30 years [49]. (See "Cervical intraepithelial neoplasia: Management of low-grade
and high-grade lesions", section on 'High grade lesions: CIN 2,3'.)
Another study looked at extended follow-up of women in over 175,000 women who had
participated in four European trials, including the study described above [105]. Compared with
women screened by cytology alone, women screened with HPV testing (largely in conjunction
with cytology) had 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). The "cost," in terms of excess number of colposcopic
procedures and biopsies performed, was not reported. In this well-screened population, the
overall incidence of invasive cervical cancer was low, with 107 cervical cancers found among
176,464 women followed for 6.5 years (1.2 million person-years).
The ongoing HPV FOCAL Study, a trial including >18,000 women aged 25 to 65 years, seeks
to examine several cytology triage strategies after initial HPV testing, compared with initial
cytology screening with HPV triage; baseline testing confirmed previous reports of greater
sensitivity for CIN 2 with initial HPV testing compared with initial cytology [104].
Co-testing (Pap test and HPV testing) In co-testing, both Pap test and HPV testing are
performed. Co-testing may detect earlier cervical abnormalities than Pap test alone, but also leads
to an increased rate of follow-up testing (colposcopy), and does not appear to affect mortality.
(See 'Compared with Pap test' above.)
A trial comparing screening with liquid based cytology with or without HPV testing in a cohort
of women aged 20 to 64 found that during the first round of screening, there was a slight
nonsignificant increase in high-grade lesions in women who had HPV testing [107]. At three
years, women who had undergone HPV testing had fewer high-grade (CIN 3+) lesions (OR
0.64, 95% CI 0.30-0.96). However, over two rounds of screening, overall rates of CIN 3 or
worse were equivalent in the two groups.
The Population Based Screening Study Amsterdam randomly assigned nearly 40,000
women aged 30 to 59 to initial screening with conventional Pap versus with Pap plus HPV
testing [108]. At five years, all women underwent both Pap and HPV testing. At the second
screening, compared with women initially screened with conventional Pap, those screened
with Pap and HPV testing had less CIN 3 or worse (88 versus 122 cases, relative risk [RR]
0.73, 95% CI 0.55-0.96) and cervical cancer (4 versus 14 cancers, RR 0.29, 95% CI 0.100.87). The cumulative detection of CIN 3 or worse and cervical cancer over the two testing
rounds, however, did not differ between the two groups. Thus, HPV testing led to earlier

detection (but not reduced incidence) of high-grade cervical lesions, including cancer. The
reduction in second-round lesions appeared to be directly attributable to a reduction in HPV
16-positive lesions.
A modeling study evaluated the risks and benefits of various screening strategies: cytology, cytology
with reflex HPV triage, co-testing (cytology and HPV), or HPV testing with reflex cytology [109]. The
study predicted that screening women with co-testing would result in nearly three times as many
colposcopies as any other strategy, but would result in a modestly lower lifetime risk of cervical
cancer.
Frequency of testing When co-testing is used as the screening method, we suggest screening
every five years if both tests are negative. A screening interval of five years provides a balance of
benefits and risks that is comparable to cytology screening every three years [47].
In large cohort studies, women who have negative co-testing have an extremely low risk (<1
percent) of developing CIN 3 or greater within the next 5 to 10 years [110-115]. As an example, a
population-based study of over 300,000 women aged 30 and older found that women who had
negative co-testing had a 0.16 percent cumulative incidence of CIN3 or worse at five years [116].
Modeling studies have shown that screening with a combination of cervical test cytology and HPV
testing every five years (for women over age 30) is as effective as screening with cervical cytology
alone every three years [47]. One modeling study comparing co-testing every three years with every
five years for women aged 40, found the longer interval to be associated with decreased
colposcopies, with only minimal change to lifetime cancer risk (0.39 percent versus 0.61 percent)
[109]. However, some argue that the increased risk for cancer is not minimal and that annual
cytology testing should be used as the gold standard for comparison for modeling studies [117].
Primary HPV testing We suggest that women age <30 years not be screened with primary HPV
testing (screening with HPV testing alone) as the poor specificity and correspondingly poor positive
predictive value limit the usefulness of HPV testing in this age group [47]. In women 30 years, the
net benefits of primary HPV testing (compared with Pap testing or co-testing) are unclear.
(See 'Women <30 years' above and 'Women 30 years' above.)
However, in the United States, the 2015 interim guidelines from the Society of Gynecologic
Oncology (SGO) and the American Society for Colposcopy and Cervical Pathology (ASCCP)
suggested primary HPV testing as an option for women starting at age 25 years (table 2) [118,119].
Other US guidelines have not made recommendations regarding primary HPV testing [106,120].
The Cobas HPV test has been approved by the FDA for primary HPV testing in women age 25
years [121].
Interim guidelines suggesting the use of primary HPV testing for cervical cancer screening may be
premature and based on insufficient evidence [106]. The FDA approval for the Cobas HPV test and
the interim guidelines from SGO/ASCCP were based on a multicenter prospective study comparing
primary HPV testing with cytology or co-testing [122]. For women 25 years, primary HPV testing
was found to be more sensitive for the detection of cervical intraepithelial neoplasia (CIN) 3 or
greater. However, limitations to this study include having only three years of follow-up data, the
outcome of CIN3 (rather than cancer), and highly structured follow up protocols that may not be
feasible in practice. Strategies that include HPV testing increase the number of positive results and
colposcopies performed and long-term outcomes are uncertain [48,49,106]. There is limited

evidence regarding optimal follow up after primary HPV testing. Data on the efficacy and cost
compared with the current standard of care (eg, Pap testing every three years or for women 30
years, co-testing every five years) are also lacking. Additionally, some have suggested that the
comparison gold standard should be annual Pap testing, rather than triennial testing [117]. Primary
HPV testing may result in more costs and procedures without clear benefits. (See 'Compared with
Pap test' above and 'Co-testing (Pap test and HPV testing)' above.)
However, primary HPV screening may be an effective screening modality in resource-poor areas.
(See "Screening for cervical cancer in resource-limited settings", section on 'HPV testing'.)
Reflex (triage) HPV testing Reflex or triage HPV testing for equivocal cytology test results
(atypical squamous cells of undetermined significance, ASC-US) may be an alternative to
conventional follow-up. (See "Cervical cytology: Evaluation of atypical squamous cells (ASC-US
and ASC-H)", section on 'HPV triage versus repeat cytology'.)
FOLLOW UP OF ABNORMAL TESTS Appropriate follow-up of abnormal tests is essential for
effective cervical cancer screening. 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 [11,123-125]. 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 [126].
Abnormal Pap test with or without HPV testing Interpretation of cytology results is discussed
elsewhere (table 4). (See "Cervical and vaginal cytology: Interpretation of results".)
Women who have abnormal Pap tests need appropriate follow-up and possibly further evaluation.
Recommendations differ depending on the woman's age, Pap test results and whether or not cotesting with HPV was done:
Atypical and malignant glandular cells (see "Cervical cytology: Evaluation of atypical and
malignant glandular cells")
Atypical squamous cells (ACC-US and ACS-H) (see "Cervical cytology: Evaluation of atypical
squamous cells (ASC-US and ASC-H)")
Low-grade squamous intraepithelial lesions (see "Cervical cytology: Evaluation of low-grade
squamous intraepithelial lesions (LSIL)")
High-grade squamous intraepithelial lesions (see "Cervical cytology: Evaluation of highgrade squamous intraepithelial lesions (HSIL)")
Cervical intraepithelial neoplasia (see "Cervical intraepithelial neoplasia: Management of lowgrade and high-grade lesions")
Unsatisfactory Pap test with or without HPV testing An unsatisfactory Pap specimen is not
reliable for evaluation of epithelial abnormalities. The management of a woman with an
unsatisfactory Pap test is discussed elsewhere. (See "Cervical and vaginal cytology: Interpretation
of results", section on 'Unsatisfactory for evaluation'.)
Abnormal HPV test, normal Pap test Co-testing (Pap test with HPV testing) is a screening
method for women 30 years. The management of a woman with abnormal HPV testing but normal
Pap testing (algorithm 1) is discussed elsewhere. (See "Cervical and vaginal cytology: Interpretation
of results", section on 'Normal cytology'.)

Abnormal HPV test, without Pap test Primary HPV testing with the Cobas test (without Pap
test) (table 3) has been approved for use in the US for women 25 years. Some United States
guidelines suggest primary HPV testing as an option for women 25 years (table 2). The US Food
and Drug Administration (FDA) approved the test 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 [106,127].
Evidence regarding optimal follow-up of an abnormal primary HPV test is lacking. One strategy is to
perform colposcopy in women who screen positive for HPV types 16 or 18 and perform a Pap test
to determine the need for colposcopy in women who screen positive for the other high-risk HPV
types [118,120,121].
IMPROVING SCREENING RATES In a survey of screening in the United States in 2010, 86.7
percent of women aged 21 to 65 years with a cervix reported having had a Pap test within the
preceding three years [14]. Older women and those without access to healthcare are more likely to
be underscreened. (See 'Epidemiology and risk factors' above and 'Inadequate prior
screening' above.)
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 [128], though even active solicitation resulted in less than a 20 percent increase
in screening in one systematic review [129]. 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 [130]. However, patient followup 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 [131,132]. 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 [133].
INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The
Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language,
at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might
have about a given condition. These articles are best for patients who want a general overview and
who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer,
more sophisticated, and more detailed. These articles are written at the 10 th 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 topics (see "Patient information: Pap tests (The Basics)")
Beyond the Basics topics (see "Patient information: Cervical cancer screening (Beyond the
Basics)" and "Patient information: Management of a cervical biopsy with precancerous cells

(Beyond the Basics)" and "Patient information: Follow-up of low-grade abnormal Pap tests
(Beyond the Basics)" and "Patient information: Follow-up of high-grade abnormal Pap tests
(Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
Cervical cancer is related to infection with specific high-risk strains of human papillomavirus
(HPV). Most risk factors for cervical cancer are related to factors that increase acquisition or
decrease clearance of HPV. Cervical cancer screening decreases incidence and mortality of
cervical cancer. (See 'Background' above.)
In the United States, we recommend that cervical cancer screening be initiated no earlier
than age 21 in immunocompetent, asymptomatic women (Grade 1A). In such women, we
suggest initiating screening at age 21, regardless of the age of initiation of sexual activity
(Grade 2C). Other countries may initiate screening at different ages (usually between 20 and
25 years). European guidelines are available from the European Cervical Cancer Association.
(See 'Initial screening' above.)
We suggest screening women age <30 years with Pap smear rather than HPV testing (either
primary HPV testing or co-testing) (Grade 2B). We screen women age <30 years with Pap
testing every three years. More frequent screening only marginally increases the detection of
cervical cancer but doubles or triples the number of downstream interventions. Primary HPV
screening may be an effective screening modality in resource-poor areas. (See 'Women <30
years' above and 'The Papanicolaou test' above and "Screening for cervical cancer in
resource-limited settings", section on 'HPV testing'.)
We suggest women age 30 years and older be screened with either Pap test every three
years or co-testing (Pap test and HPV testing) every five years if both initial tests are negative
(Grade 2B). Co-testing may detect cervical abnormalities earlier than Pap test alone, although
it also leads to an increased rate of follow-up testing. (See 'Women 30 years' above and 'Cotesting (Pap test and HPV testing)' above.)
Earlier initiation and/or more frequent screening may be warranted for women in specific
populations (eg, immunocompromised, in utero exposure to diethylstilbestrol). (See 'Special
populations' above.)
In general, we suggest that women aged 65 and older who have had adequate negative prior
screening (three consecutive negative Pap tests or two consecutive negative co-tests within
the previous 10 years, with the most recent test within the previous five years) not undergo
screening for cervical cancer (Grade 2C). We continue to offer screening for cervical cancer to
women with a good life expectancy who have risk factors for cervical cancer (a history of an
abnormal Pap test, current smoker or history of smoking, unknown prior Pap test history,
previous HPV-related disease, or new partners) beyond age 65 years (generally until about
age 80, but the upper limit of offering screening may vary with the risk factor).
(See 'Discontinuing screening' above and "Cervical intraepithelial neoplasia: Treatment and
follow-up", section on 'Subsequent screening'.)
We generally screen older women who have not been adequately screened with either Pap
test every two to three years or co-testing every five years until age 70 or 75 years.
(See 'Inadequate prior screening' above.)
Most cervical cancer occurs in women who have never been screened or who have had only
sporadic screening. (See 'Epidemiology and risk factors' above.)

The effectiveness of screening also hinges on adequate follow-up and treatment for
abnormal results. (See 'Follow up of abnormal tests' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
REFERENCES
1.

Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011; 61:69.

2.

Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary
cause of invasive cervical cancer worldwide. J Pathol 1999; 189:12.

3.

Nobbenhuis MA, Walboomers JM, Helmerhorst TJ, et al. Relation of human papillomavirus
status to cervical lesions and consequences for cervical-cancer screening: a prospective study.
Lancet 1999; 354:20.

4.

Kjaer SK, van den Brule AJ, Paull G, et al. Type specific persistence of high risk human
papillomavirus (HPV) as indicator of high grade cervical squamous intraepithelial lesions in young
women: population based prospective follow up study. BMJ 2002; 325:572.

5.

Wallin KL, Wiklund F, Angstrm T, et al. Type-specific persistence of human papillomavirus

DNA before the development of invasive cervical cancer. N Engl J Med 1999; 341:1633.

6.

Committee on Practice BulletinsGynecology. ACOG Practice Bulletin Number 131:

Screening for cervical cancer. Obstet Gynecol 2012; 120:1222.

7.

Klumb EM, Arajo ML Jr, Jesus GR, et al. Is higher prevalence of cervical intraepithelial
neoplasia in women with lupus due to immunosuppression? J Clin Rheumatol 2010; 16:153.

8.

Kahn JA. HPV vaccination for the prevention of cervical intraepithelial neoplasia. N Engl J
Med 2009; 361:271.

9.

Ho GY, Bierman R, Beardsley L, et al. Natural history of cervicovaginal papillomavirus

infection in young women. N Engl J Med 1998; 338:423.

10.

Janerich DT, Hadjimichael O, Schwartz PE, et al. The screening histories of women with
invasive cervical cancer, Connecticut. Am J Public Health 1995; 85:791.

11.

Coleman DV, Poznansky JJ. Review of cervical smears from 76 women with invasive
cervical cancer: cytological findings and medicolegal implications. Cytopathology 2006; 17:127.

12.

Abed Z, O'Leary M, Hand K, et al. Cervical screening history in patients with early stage
carcinoma of the cervix. Ir Med J 2006; 99:140.

13.

Ponka D, Dickinson J. Screening with the Pap test. CMAJ 2014; 186:1394.

14.

Jemal A, Simard EP, Dorell C, et al. Annual Report to the Nation on the Status of Cancer,
1975-2009, featuring the burden and trends in human papillomavirus(HPV)-associated cancers and
HPV vaccination coverage levels. J Natl Cancer Inst 2013; 105:175.

15.

Vitals signs: Cervical cancer incidence, mortality and screening - United States, 2007-2012.
MMWR. Nov 5, 2014 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm63e1105a1.htm (Accessed
on November 06, 2014).

16.

Sabatino SA, White MC, Thompson TD, et al. Cancer screening test use - United States,
2013. MMWR Morb Mortal Wkly Rep 2015; 64:464.

17.

Lofters A, Guilcher S, Glazier RH, et al. Screening for cervical cancer in women with
disability and multimorbidity: a retrospective cohort study in Ontario, Canada. CMAJ Open 2014;
2:E240.

18.

Cervical cancer screening programs. I. Epidemiology and natural history of carcinoma of

the cervix. Can Med Assoc J 1976; 114:1003.

19.

Johannesson G, Geirsson G, Day N. The effect of mass screening in Iceland, 1965-74, on

the incidence and mortality of cervical carcinoma. Int J Cancer 1978; 21:418.

20.

Cannistra SA, Niloff JM. Cancer of the uterine cervix. N Engl J Med 1996; 334:1030.

21.

Nieminen P, Kallio M, Hakama M. The effect of mass screening on incidence and mortality
of squamous and adenocarcinoma of cervix uteri. Obstet Gynecol 1995; 85:1017.

22.

Bergstrm R, Sparn P, Adami HO. Trends in cancer of the cervix uteri in Sweden following
cytological screening. Br J Cancer 1999; 81:159.

23.

Benedet JL, Anderson GH, Matisic JP. A comprehensive program for cervical cancer
detection and management. Am J Obstet Gynecol 1992; 166:1254.

24.

Nygrd JF, Skare GB, Thoresen S. The cervical cancer screening programme in Norway,
1992-2000: changes in Pap smear coverage and incidence of cervical cancer. J Med Screen 2002;
9:86.

25.

Taylor R, Morrell S, Mamoon H, et al. Decline in cervical cancer incidence and mortality in
New South Wales in relation to control activities (Australia). Cancer Causes Control 2006; 17:299.

26.

Aklimunnessa K, Mori M, Khan MM, et al. Effectiveness of cervical cancer screening over
cervical cancer mortality among Japanese women. Jpn J Clin Oncol 2006; 36:511.

27.

Vaccarella S, Franceschi S, Engholm G, et al. 50 years of screening in the Nordic countries:

quantifying the effects on cervical cancer incidence. Br J Cancer 2014; 111:965.

28.

Peirson L, Fitzpatrick-Lewis D, Ciliska D, Warren R. Screening for cervical cancer: a

systematic review and meta-analysis. Syst Rev 2013; 2:35.

29.

Whitlock EP, Vesco KK, Eder M, et al. Liquid-based cytology and human papillomavirus
testing to screen for cervical cancer: a systematic review for the U.S. Preventive Services Task
Force. Ann Intern Med 2011; 155:687.

30.

Gibb RK, Martens MG. The impact of liquid-based cytology in decreasing the incidence of
cervical cancer. Rev Obstet Gynecol 2011; 4:S2.

31.

Andrae B, Andersson TM, Lambert PC, et al. Screening and cervical cancer cure:
population based cohort study. BMJ 2012; 344:e900.

32.

Clarke EA, Anderson TW. Does screening by "Pap" smears help prevent cervical cancer? A
case-control study. Lancet 1979; 2:1.

33.

Bell S, Porter M, Kitchener H, et al. Psychological response to cervical screening. Prev Med
1995; 24:610.

34.

Gray NM, Sharp L, Cotton SC, et al. Psychological effects of a low-grade abnormal cervical
smear test result: anxiety and associated factors. Br J Cancer 2006; 94:1253.

35.

Peters T, Somerset M, Baxter K, Wilkinson C. Anxiety among women with mild dyskaryosis:
a randomized trial of an educational intervention. Br J Gen Pract 1999; 49:348.

36.

Maissi E, Marteau TM, Hankins M, et al. Psychological impact of human papillomavirus

testing in women with borderline or mildly dyskaryotic cervical smear test results: cross sectional
questionnaire study. BMJ 2004; 328:1293.

37.

Wilt TJ, Harris RP, Qaseem A, High Value Care Task Force of the American College of
Physicians. Screening for cancer: advice for high-value care from the american college of
physicians. Ann Intern Med 2015; 162:718.

38.

European Cervical Cancer Association. http://www.ecca.info/ (Accessed on December 16,

2014).

39.

American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 463:
Cervical cancer in adolescents: screening, evaluation, and management. Obstet Gynecol 2010;
116:469.

40.

Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M,
Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer
Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, based on November 2013
SEER data submission, posted to the SEER web site, April 2014.
http://seer.cancer.gov/csr/1975_2011.

41.

Mount SL, Papillo JL. A study of 10,296 pediatric and adolescent Papanicolaou smear
diagnoses in northern New England. Pediatrics 1999; 103:539.

42.

Edelman M, Fox AS, Alderman EM, et al. Cervical Papanicolaou smear abnormalities in
inner city Bronx adolescents: prevalence, progression, and immune modifiers. Cancer 1999;
87:184.

43.

Moscicki AB, Shiboski S, Hills NK, et al. Regression of low-grade squamous intra-epithelial
lesions in young women. Lancet 2004; 364:1678.

44.

Schlecht NF, Platt RW, Duarte-Franco E, et al. Human papillomavirus infection and time to
progression and regression of cervical intraepithelial neoplasia. J Natl Cancer Inst 2003; 95:1336.

45.

Szarewski A, Sasieni P. Cervical screening in adolescents--at least do no harm. Lancet

2004; 364:1642.

46.

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.

47.

Moyer VA, U.S. Preventive Services Task Force. Screening for cervical cancer: U.S.
Preventive Services Task Force recommendation statement. Ann Intern Med 2012; 156:880.

48.

Ronco G, Giorgi-Rossi P, Carozzi F, et al. Efficacy of human papillomavirus testing for the
detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled
trial. Lancet Oncol 2010; 11:249.

49.

Castle PE, Katki HA. Benefits and risks of HPV testing in cervical cancer screening. Lancet
Oncol 2010; 11:214.

50.

Leinonen M, Nieminen P, Kotaniemi-Talonen L, et al. Age-specific evaluation of primary

human papillomavirus screening vs conventional cytology in a randomized setting. J Natl Cancer
Inst 2009; 101:1612.

51.

Vesco KK, Whitlock EP, Eder M, et al. Risk factors and other epidemiologic considerations
for cervical cancer screening: a narrative review for the U.S. Preventive Services Task Force. Ann
Intern Med 2011; 155:698.

52.

Sawaya GF, Kerlikowske K, Lee NC, et al. Frequency of cervical smear abnormalities within
3 years of normal cytology. Obstet Gynecol 2000; 96:219.

53.

Yasmeen S, Romano PS, Pettinger M, et al. Incidence of cervical cytological abnormalities

with aging in the women's health initiative: a randomized controlled trial. Obstet Gynecol 2006;
108:410.

54.

Insinga RP, Glass AG, Rush BB. Diagnoses and outcomes in cervical cancer screening: a
population-based study. Am J Obstet Gynecol 2004; 191:105.

55.

Lawson HW, Lee NC, Thames SF, et al. Cervical cancer screening among low-income
women: results of a national screening program, 1991-1995. Obstet Gynecol 1998; 92:745.

56.

Sawaya GF, Grady D, Kerlikowske K, et al. The positive predictive value of cervical smears
in previously screened postmenopausal women: the Heart and Estrogen/progestin Replacement
Study (HERS). Ann Intern Med 2000; 133:942.

57.

Saad RS, Dabbs DJ, Kordunsky L, et al. Clinical significance of cytologic diagnosis of
atypical squamous cells, cannot exclude high grade, in perimenopausal and postmenopausal
women. Am J Clin Pathol 2006; 126:381.

58.

Rositch AF, Nowak RG, Gravitt PE. Increased age and race-specific incidence of cervical
cancer after correction for hysterectomy prevalence in the United States from 2000 to 2009. Cancer
2014; 120:2032.

59.

Kamineni A, Weinmann S, Shy KK, et al. Efficacy of screening in preventing cervical cancer
among older women. Cancer Causes Control 2013; 24:1653.

60.

Rustagi AS, Kamineni A, Weinmann S, et al. Cervical screening and cervical cancer death
among older women: a population-based, case-control study. Am J Epidemiol 2014; 179:1107.

61.

Rebolj M, van Ballegooijen M, Lynge E, et al. Incidence of cervical cancer after several
negative smear results by age 50: prospective observational study. BMJ 2009; 338:b1354.

62.

Fletcher A. Screening for cancer of the cervix in elderly women. Lancet 1990; 335:97.

63.

Fahs MC, Mandelblatt J, Schechter C, Muller C. Cost effectiveness of cervical cancer

screening for the elderly. Ann Intern Med 1992; 117:520.

64.

Power EJ. Pap smears, elderly women, and Medicare. Cancer Invest 1993; 11:164.

65.

Wright TC Jr, Ellerbrock TV, Chiasson MA, et al. Cervical intraepithelial neoplasia in women
infected with human immunodeficiency virus: prevalence, risk factors, and validity of Papanicolaou
smears. New York Cervical Disease Study. Obstet Gynecol 1994; 84:591.

66.

Ellerbrock TV, Chiasson MA, Bush TJ, et al. Incidence of cervical squamous intraepithelial
lesions in HIV-infected women. JAMA 2000; 283:1031.

67.

Moscicki AB, Ellenberg JH, Crowley-Nowick P, et al. Risk of high-grade squamous

intraepithelial lesion in HIV-infected adolescents. J Infect Dis 2004; 190:1413.

68.

Nguyen ML, Flowers L. Cervical cancer screening in immunocompromised women. Obstet

Gynecol Clin North Am 2013; 40:339.

69.

Nath R, Mant C, Luxton J, et al. High risk of human papillomavirus type 16 infections and of
development of cervical squamous intraepithelial lesions in systemic lupus erythematosus patients.
Arthritis Rheum 2007; 57:619.

70.

Kiss E, Kovacs L, Szodoray P. Malignancies in systemic lupus erythematosus. Autoimmun

Rev 2010; 9:195.

71.

Tam LS, Chan PK, Ho SC, et al. Risk factors for squamous intraepithelial lesions in
systemic lupus erythematosus: a prospective cohort study. Arthritis Care Res (Hoboken) 2011;
63:269.

72.

Klumb EM, Pinto AC, Jesus GR, et al. Are women with lupus at higher risk of HPV
infection? Lupus 2010; 19:1485.

73.

Sirovich BE, Welch HG. Cervical cancer screening among women without a cervix. JAMA
2004; 291:2990.

74.

Bell J, Sevin BU, Averette H, Nadji M. Vaginal cancer after hysterectomy for benign
disease: value of cytologic screening. Obstet Gynecol 1984; 64:699.

75.

McIntosh DG. Pap smear screening after hysterectomy. Compr Ther 1998; 24:14.

76.

Ferris DG, Messing MJ, Crosby JH. Vaginal intraepithelial neoplasia III detected after
hysterectomy for benign conditions. J Fam Pract 1995; 40:81.

77.

Dvila RM, Miranda MC. Vaginal intraepithelial neoplasia and the Pap smear. Acta Cytol
2000; 44:137.

78.

Fetters MD, Fischer G, Reed BD. Effectiveness of vaginal Papanicolaou smear screening
after total hysterectomy for benign disease. JAMA 1996; 275:940.

79.

Piscitelli JT, Bastian LA, Wilkes A, Simel DL. Cytologic screening after hysterectomy for
benign disease. Am J Obstet Gynecol 1995; 173:424.

80.

Pearce KF, Haefner HK, Sarwar SF, Nolan TE. Cytopathological findings on vaginal
Papanicolaou smears after hysterectomy for benign gynecologic disease. N Engl J Med 1996;
335:1559.

81.

Fox J, Remington P, Layde P, Klein G. The effect of hysterectomy on the risk of an

abnormal screening Papanicolaou test result. Am J Obstet Gynecol 1999; 180:1104.

82.

Videlefsky A, Grossl N, Denniston M, et al. Routine vaginal cuff smear testing in posthysterectomy patients with benign uterine conditions: when is it indicated? J Am Board Fam Pract
2000; 13:233.

83.

Farghaly H, Bourgeois D, Houser PM, et al. Routine vaginal Pap test is not useful in women
status-post hysterectomy for benign disease. Diagn Cytopathol 2006; 34:640.

84.

National Cancer Institute. Clinician information: Identification and management of persons

exposed to DES (Diethylstilbestrol). http://www.cancer.gov/cancertopics/causes/des/personsexposed-to-des (Accessed on June 14, 2012).

85.

US Food and Drug Administration. FDA News. FDA licenses new vaccine for prevention of
cervical cancer and other diseases in females caused by Human Papillomavirus. Released June 8,
2006. Available at: www.fda.gov/bbs/topics/NEWS/2006/NEW01385.html (Accessed on September
20, 2007).

86.

Saslow D, Castle PE, Cox JT, et al. American Cancer Society Guideline for human
papillomavirus (HPV) vaccine use to prevent cervical cancer and its precursors. CA Cancer J Clin
2007; 57:7.

87.

Nanda K, McCrory DC, Myers ER, et al. Accuracy of the Papanicolaou test in screening for
and follow-up of cervical cytologic abnormalities: a systematic review. Ann Intern Med 2000;
132:810.

88.

Stoler MH, Schiffman M, Atypical Squamous Cells of Undetermined Significance-Low-grade

Squamous Intraepithelial Lesion Triage Study (ALTS) Group. Interobserver reproducibility of
cervical cytologic and histologic interpretations: realistic estimates from the ASCUS-LSIL Triage
Study. JAMA 2001; 285:1500.

89.

Sasieni P, Castanon A, Cuzick J. Screening and adenocarcinoma of the cervix. Int J Cancer
2009; 125:525.

90.

Arbyn M, Bergeron C, Klinkhamer P, et al. Liquid compared with conventional cervical

cytology: a systematic review and meta-analysis. Obstet Gynecol 2008; 111:167.

91.

Davey E, Barratt A, Irwig L, et al. Effect of study design and quality on unsatisfactory rates,
cytology classifications, and accuracy in liquid-based versus conventional cervical cytology: a
systematic review. Lancet 2006; 367:122.

92.

Lee KR, Ashfaq R, Birdsong GG, et al. Comparison of conventional Papanicolaou smears
and a fluid-based, thin-layer system for cervical cancer screening. Obstet Gynecol 1997; 90:278.

93.

Kulasingam SL, Havrilesky L, Ghebre R, Myers ER. Screening for Cerivcal Cancer: A
decision analysis for the U.S. Preventeive SErvices Task Force.
http://www.uspreventiveservicestaskforce.org/uspstf11/cervcancer/cervcancerdecan.pdf (Accessed
on April 06, 2012).

94.

Screening for squamous cervical cancer: duration of low risk after negative results of
cervical cytology and its implication for screening policies. IARC Working Group on evaluation of
cervical cancer screening programmes. Br Med J (Clin Res Ed) 1986; 293:659.

95.

Sawaya GF, McConnell KJ, Kulasingam SL, et al. Risk of cervical cancer associated with
extending the interval between cervical-cancer screenings. N Engl J Med 2003; 349:1501.

96.

American Society for Colposcopy and Cervical Pathology. 2006 consensus guidelines for
the management of women with abnormal cervical cancer screening tests. 2009 addendum.
Available at: www.guideline.gov/summary/summary.aspx?doc_id=14698&nbr=007268&string=HPV
(Accessed on August 24, 2009).

97.

ASCUS-LSIL Traige Study (ALTS) Group. A randomized trial on the management of lowgrade squamous intraepithelial lesion cytology interpretations. Am J Obstet Gynecol 2003;
188:1393.

98.

Cuzick J, Clavel C, Petry KU, et al. Overview of the European and North American studies
on HPV testing in primary cervical cancer screening. Int J Cancer 2006; 119:1095.

99.

Kim JJ, Wright TC, Goldie SJ. Cost-effectiveness of human papillomavirus DNA testing in
the United Kingdom, The Netherlands, France, and Italy. J Natl Cancer Inst 2005; 97:888.

100.
Denny LA, Wright TC Jr. Human papillomavirus testing and screening. Best Pract Res Clin
Obstet Gynaecol 2005; 19:501.
101.
Koliopoulos G, Arbyn M, Martin-Hirsch P, et al. Diagnostic accuracy of human
papillomavirus testing in primary cervical screening: a systematic review and meta-analysis of nonrandomized studies. Gynecol Oncol 2007; 104:232.
102.
Mayrand MH, Duarte-Franco E, Rodrigues I, et al. Human papillomavirus DNA versus
Papanicolaou screening tests for cervical cancer. N Engl J Med 2007; 357:1579.
103.
Leinonen MK, Nieminen P, Lnnberg S, et al. Detection rates of precancerous and
cancerous cervical lesions within one screening round of primary human papillomavirus DNA
testing: prospective randomised trial in Finland. BMJ 2012; 345:e7789.
104.
Ogilvie GS, Krajden M, van Niekerk DJ, et al. Primary cervical cancer screening with HPV
testing compared with liquid-based cytology: results of round 1 of a randomised controlled trial -- the
HPV FOCAL Study. Br J Cancer 2012; 107:1917.
105.
Ronco G, Dillner J, Elfstrm KM, et al. Efficacy of HPV-based screening for prevention of
invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet 2014;
383:524.
106.
Feldman S. Human papillomavirus testing for primary cervical cancer screening: is it time to
abandon Papanicolaou testing? JAMA Intern Med 2014; 174:1539.
107.
Kitchener HC, Almonte M, Thomson C, et al. HPV testing in combination with liquid-based
cytology in primary cervical screening (ARTISTIC): a randomised controlled trial. Lancet Oncol
2009; 10:672.
108.
Rijkaart DC, Berkhof J, Rozendaal L, et al. Human papillomavirus testing for the detection
of high-grade cervical intraepithelial neoplasia and cancer: final results of the POBASCAM
randomised controlled trial. Lancet Oncol 2012; 13:78.
109.
Stout NK, Goldhaber-Fiebert JD, Ortendahl JD, Goldie SJ. Trade-offs in cervical cancer
prevention: balancing benefits and risks. Arch Intern Med 2008; 168:1881.

110.
Dillner J, Rebolj M, Birembaut P, et al. Long term predictive values of cytology and human
papillomavirus testing in cervical cancer screening: joint European cohort study. BMJ 2008;
337:a1754.
111.

Sherman ME, Lorincz AT, Scott DR, et al. Baseline cytology, human papillomavirus testing,
and risk for cervical neoplasia: a 10-year cohort analysis. J Natl Cancer Inst 2003; 95:46.

112.
Kjr SK, Frederiksen K, Munk C, Iftner T. Long-term absolute risk of cervical intraepithelial
neoplasia grade 3 or worse following human papillomavirus infection: role of persistence. J Natl
Cancer Inst 2010; 102:1478.
113.
Wright TC Jr, Schiffman M, Solomon D, et al. Interim guidance for the use of human
papillomavirus DNA testing as an adjunct to cervical cytology for screening. Obstet Gynecol 2004;
103:304.
114.
Kjaer S, Hgdall E, Frederiksen K, et al. The absolute risk of cervical abnormalities in highrisk human papillomavirus-positive, cytologically normal women over a 10-year period. Cancer Res
2006; 66:10630.
115.
Khan MJ, Castle PE, Lorincz AT, et al. The elevated 10-year risk of cervical precancer and
cancer in women with human papillomavirus (HPV) type 16 or 18 and the possible utility of typespecific HPV testing in clinical practice. J Natl Cancer Inst 2005; 97:1072.
116.
Katki HA, Kinney WK, Fetterman B, et al. Cervical cancer risk for women undergoing
concurrent testing for human papillomavirus and cervical cytology: a population-based study in
routine clinical practice. Lancet Oncol 2011; 12:663.
117.
Kinney W, Wright TC, Dinkelspiel HE, et al. Increased cervical cancer risk associated with
screening at longer intervals. Obstet Gynecol 2015; 125:311.
118.
Huh WK, Ault KA, Chelmow D, et al. Use of primary high-risk human papillomavirus testing
for cervical cancer screening: interim clinical guidance. Obstet Gynecol 2015; 125:330.
119.
Huh WK, Ault KA, Chelmow D, et al. Use of primary high-risk human papillomavirus testing
for cervical cancer screening: interim clinical guidance. J Low Genit Tract Dis 2015; 19:91.
120.
Perkins RB, Stier EA. Should U.S. women be screened for cervical cancer with pap tests,
HPV tests, or both? Ann Intern Med 2014; 161:295.
121.
FDA approves first human papillomavirus test for primary cervical cancer screening.
http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm394773.htm (Accessed on
November 24, 2014).
122.
Wright TC, Stoler MH, Behrens CM, et al. Primary cervical cancer screening with human
papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening
test. Gynecol Oncol 2015; 136:189.
123.
Leyden WA, Manos MM, Geiger AM, et al. Cervical cancer in women with comprehensive
health care access: attributable factors in the screening process. J Natl Cancer Inst 2005; 97:675.
124.
Sung HY, Kearney KA, Miller M, et al. Papanicolaou smear history and diagnosis of
invasive cervical carcinoma among members of a large prepaid health plan. Cancer 2000; 88:2283.

125.
Stuart GC, McGregor SE, Duggan MA, Nation JG. Review of the screening history of
Alberta women with invasive cervical cancer. CMAJ 1997; 157:513.
126.
Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J
Cancer 2006; 118:3030.
127.
Wright TC Jr, Stoler MH, Behrens CM, et al. The ATHENA human papillomavirus study:
design, methods, and baseline results. Am J Obstet Gynecol 2012; 206:46.e1.
128.
Forbes C, Jepson R, Martin-Hirsch P. Interventions targeted at women to encourage the
uptake of cervical screening. Cochrane Database Syst Rev 2002; :CD002834.
129.
Yabroff KR, Mangan P, Mandelblatt J. Effectiveness of interventions to increase
Papanicolaou smear use. J Am Board Fam Pract 2003; 16:188.
130.
Batal H, Biggerstaff S, Dunn T, Mehler PS. Cervical cancer screening in the urgent care
setting. J Gen Intern Med 2000; 15:389.
131.
ACOG Committee on Quality Improvement and Patient Safety. ACOG committee opinion
#329. Tracking and reminder systems. Obstet Gynecol 2006; 107:745.
132.
Gordon NP, Hiatt RA, Lampert DI. Concordance of self-reported data and medical record
audit for six cancer screening procedures. J Natl Cancer Inst 1993; 85:566.
133.
Everett T, Bryant A, Griffin MF, et al. Interventions targeted at women to encourage the
uptake of cervical screening. Cochrane Database Syst Rev 2011; :CD002834.
Topic 7575 Version 50.0

http://www.uptodate.com/contents/screening-for-cervical-cancer?
source=search_result&search=vph&selectedTitle=8~150