interim update

The American College of

Obstetricians and Gynecologists
WOMEN’S HEALTH CARE PHYSICIANS

P RACTICE BULLET IN
clinical management guidelines for obstetrician – gynecologists

Number 168, October 2016 (Replaces Practice Bulletin Number 157, January 2016)
(Reaffirmed 2018)

INTERIM UPDATE: This Practice Bulletin is updated to reflect limited, focused changes in the recommendations for
cervical cancer screening in adolescents and young women who are infected with human immunodeficiency virus or
who are otherwise immunocompromised.

Cervical Cancer Screening and Prevention

The incidence of cervical cancer in the United States has decreased more than 50% in the past 30 years because
of widespread screening. In 1975, the rate was 14.8 per 100,000 women. By 2011, it decreased to 6.7 per 100,000
women. Mortality from the disease has undergone a similar decrease from 5.55 per 100,000 women in 1975 to
2.3 per 100,000 women in 2011 (1). The American Cancer Society (ACS) estimated that there would be 12,900 new
cases of cervical cancer in the United States in 2015, with 4,100 deaths from the disease (2). Cervical cancer is much
more common worldwide, particularly in countries without screening programs, with an estimated 527,624 new cases
of the disease and 265,672 resultant deaths each year (3). When cervical cancer screening programs have been intro-
duced into communities, marked reductions in cervical cancer incidence have followed (4, 5).
New technologies for cervical cancer screening continue to evolve, as do recommendations for managing the
results. In addition, there are different risk–benefit considerations for women at different ages, as reflected in age-
specific screening recommendations. In 2011, the ACS, the American Society for Colposcopy and Cervical Pathology
(ASCCP), and the American Society for Clinical Pathology (ASCP) updated their joint guidelines for cervical cancer
screening (6), as did the U.S. Preventive Services Task Force (USPSTF) (7). Subsequently, in 2015, ASCCP and the
Society of Gynecologic Oncology (SGO) issued interim guidance for the use of a human papillomavirus (HPV) test for
primary screening for cervical cancer that was approved in 2014 by the U.S. Food and Drug Administration (FDA)
(8). The purpose of this document is to provide a review of the best available evidence regarding the prevention and
early detection of cervical cancer.

Background the United States, those lacking a regular source of health

care, and the uninsured are at especially high risk (14).
Most cases of cervical cancer occur in women who were
either never screened or were screened inadequately (9, Natural History of Cervical Neoplasia
10). Estimates suggest that 50% of the women in whom Human papillomavirus is divided into two classes:
cervical cancer is diagnosed never had cervical cytology 1) oncogenic and 2) nononcogenic. Infection with onco-
testing, and another 10% had not been screened within genic (or high-risk) HPV usually is a necessary but not
the 5 years before diagnosis (11–13). Additional public sufficient factor for the development of squamous cervi-
health measures remain critical to improving access to cal neoplasia. Therefore, only a small fraction of women
screening for this group of women, who often are unin- infected with high-risk HPV will develop significant
sured or underinsured. Although rates of cervical cancer cervical abnormalities and cancer. The current model
are decreasing in women born in the United States who of cervical carcinogenesis posits that HPV infection
have access to screening, women who are immigrants to results in either transient or persistent infection (15, 16).

Committee on Practice Bulletins—Gynecology. This Practice Bulletin was developed by the Committee on Practice Bulletins—Gynecology in collabora-
tion with David Chelmow, MD.
The information is designed to aid practitioners in making decisions about appropriate obstetric and gynecologic care. These guidelines should not be
construed as dictating an exclusive course of treatment or procedure. Variations in practice may be warranted based on the needs of the individual patient,
resources, and limitations unique to the institution or type of practice.
Most HPV infection is transient and poses little risk and the College of American Pathologists to adopt a
of progression. Only a small fraction of infections are revised two-tiered histologic classification (low-grade
persistent, but persistent infection at 1 year and 2 years squamous intraepithelial lesions [LSILs] and HSILs),
after initial infection strongly predicts subsequent risk which eliminated CIN 2 as a separate category (43). In a
of cervical intraepithelial neoplasia (CIN) 3 or cancer cohort of untreated patients with CIN 3, the cumulative
regardless of age (6, 17, 18). incidence of invasive cancer was reported to be 30.1%
Factors that determine which HPV infections will at 30 years, which is evidence that CIN 3 poses a signifi-
persist are incompletely understood. The HPV geno- cant risk of progression to cancer (44).
type appears to be the most important determinant of In evaluating appropriate screening intervals, it
persistence and progression. Human papillomavirus-16 is important to consider the time required for disease
has the highest carcinogenic potential and accounts for progression. Most HPV-related types of cervical neo-
approximately 55–60% of all cases of cervical cancer plasia progress very slowly. Time from development of
worldwide. Human papillomavirus-18 is the next most CIN 3 to cancer is not precisely known, but the 10-year
carcinogenic genotype and is responsible for 10–15% difference in age of diagnosis between screen-detected
of cases of cervical cancer. Approximately 12 other CIN 3 and cancer suggests long average sojourn time in
genotypes are associated with the remainder of cases of the precancerous state (23). This rather indolent disease
cervical cancer (19–21). Known cofactors that increase course is well suited to less frequent testing (ie, at inter-
the likelihood of persistent HPV infection include vals longer than 1 year).
cigarette smoking, a compromised immune system, and
human immunodeficiency virus (HIV) infection (22, 23). Cervical Cytology Screening Techniques
Human papillomavirus infection is most common in
Liquid-based and conventional methods of cervical
teenagers and women in their early 20s, with a decrease
cytology specimen collection are acceptable for screen-
in prevalence as women age (24–27). Most young
ing. Exfoliated cells are collected from the transforma-
women, especially those younger than 21 years, have
an effective immune response that clears the infection tion zone of the cervix and transferred to a vial of liquid
in an average of 8 months or decreases the viral load to preservative that is processed in the laboratory (liquid-
undetectable levels (in 85–90% of women) in an average based technique) or transferred directly to a slide and
of 8–24 months (28–34). Concomitant with infection fixed (conventional technique). Blood, discharge, and
resolution, most cervical neoplasia also will resolve some lubricants (including personal lubricants used by
spontaneously in this population (33–38). patients) may interfere with specimen interpretation. Use
The natural course of an HPV infection does not of a small amount of water-based lubricant with specu-
appear to vary with age in women aged 30–65 years (39). lum examination has been shown to decrease exami-
Newly acquired HPV infection appears to have the same nation discomfort compared with use of water alone
low chance of persistence regardless of age in women (45–47). At least one manufacturer has a list of lubri-
30 years and older (39). However, HPV infection cants that have been confirmed not to contain interfering
detected in women older than 30 years is more likely to substances (48–50). If a water-based lubricant is used,
reflect persistent infection. This correlates with increas- it is important to minimize the amount that comes into
ing rates of occurrence of high-grade squamous intraepi- contact with the cervix and to choose one that is consis-
thelial lesions (HSILs) with increasing age (39). tent with the recommendations of the manufacturer of
Given that low-grade neoplasia (or CIN 1) is a man- the liquid-based collection kit. A small amount of water-
ifestation of acute HPV infection, there is a high rate soluble lubricant on the speculum does not decrease the
of regression to normal histology results, leading to quality of cervical cytology test results. Four published
current recommendations for observation rather than randomized controlled trials that assessed the effect of
treatment of these cases (40). The clinical approach to lubrication on conventional cytology demonstrated no
CIN 2 is currently controversial because of the chal- effect on the quality of cervical cytology test results
lenge in accurate diagnosis as well as the uncertainty (51–55). Use of a large amount of lubricant applied
about ideal management. The diagnosis of CIN 2 has directly to the cervix (ie, a 1–1.5-cm ribbon of lubricant
a high degree of interobserver variability. Furthermore, directly applied to the cervical os) can affect specimen
the prognosis of CIN 2 lesions seems to represent a mix adequacy (50), but this is not standard clinical practice.
of low-grade and high-grade lesions that cannot be dif- In a retrospective review of 4,068 liquid-based Pap test
ferentiated easily by histology, rather than representing a specimens, 0.4% had obscuring material that caused
specific intermediate lesion (41, 42). Concerns about the misinterpretation of results, with roughly one half of
limitations of the CIN 2 categorization led the ASCCP these cases possibly related to lubricant use (49).

2 Practice Bulletin No. 168

 The liquid-based method of cervical cytology speci- show an appreciable difference in sensitivity or specific-
men collection has the advantage of allowing a single ity for the detection of CIN compared with the conven-
specimen to be used to perform cytology, HPV testing, tional cervical cytology screening technique (56, 57).
and testing for gonorrhea and chlamydial infection.
Despite several theoretic advantages of the liquid-based Cytologic Test Result Reporting
technique, including easier interpretation, filtering of The Bethesda System of cervical cytologic test result
blood and debris, and fewer unsatisfactory results, a meta- reporting generally is accepted in the United States (see
analysis of eight studies and a randomized trial did not Box 1). It has undergone three revisions since 1988 (58).

Box 1. The 2014 Bethesda System for Reporting Cervical Cytology ^

Specimen Type
Indicate: conventional test (Pap test), liquid-based preparation, or 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)
• Unsatisfactory for evaluation (specify reason)
— Specimen rejected or 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/Result (eg, endometrial cells in a woman 45 years of age or older)
• Epithelial cell abnormality: see Interpretation/Result (specify “squamous” or “glandular” as appropriate)
Interpretation/Result
• Negative for intraepithelial lesion or malignancy (when there is no cellular evidence of neoplasia, state this in the General
Categorization section, in the Interpretation/Result section, or both—whether or not there are organisms or other non-
neoplastic findings)
— Nonneoplastic findings (optional to report; list not inclusive)
Nonneoplastic 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 device
Glandular cells status posthysterectomy
— Organisms
Trichomonas vaginalis
Fungal organisms morphologically consistent with Candida species
Shift in flora suggestive of bacterial vaginosis
Bacteria morphologically consistent with Actinomyces species
(continued)

Practice Bul­le­tin No. 168 3

 Box 1. The 2014 Bethesda System for Reporting Cervical Cytology (continued)
Interpretation/Result (continued)
• Negative for intraepithelial lesion or malignancy (continued)
— Organisms (continued)
Cellular changes consistent with herpes simplex virus
Cellular changes consistent with cytomegalovirus
• Other
— Endometrial cells (in a woman 45 years of age or older) (specify if “negative for squamous intraepithelial lesion”)
• Epithelial cell abnormalities
— Squamous cell
Atypical squamous cells (ACS)
 Of undetermined significance (ASC-US)
 Cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H)
Low-grade squamous intraepithelial lesion (LSIL) (encompassing: human papillomavirus/mild dysplasia/cervical
intraepithelial neoplasia (CIN) 1
High-grade squamous intraepithelial lesion (encompassing: moderate and severe dysplasia, carcinoma in situ; CIN 2,
and CIN 3)
 With features suspicious for invasion (if invasion is suspected)
Squamous cell carcinoma
— Glandular cell
Atypical
 Endocervical cells (not otherwise specified or specify in comments)
 Endometrial cells (not otherwise specified or specify in comments)
 Glandular cells (not otherwise specified or specify in comments)
Atypical
 Endocervical cells, favor neoplastic
 Glandular cells, favor neoplastic
Endocervical adenocarcinoma in situ
Adenocarcinoma
 Endocervical
 Endometrial
 Extrauterine
 Not otherwise specified
• 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 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).
Reprinted from Nayar R, Wilbur DC, editors. The Bethesda system for reporting cervical cytology: definitions, criteria, and explanatory notes. 3rd ed. New
York (NY): Springer; 2015. With permission of Springer.

4 Practice Bulletin No. 168

Human Papillomavirus cines shown to be effective at preventing HPV infection:
1) a bivalent vaccine, which covers HPV-16 and HPV-18;
Testing 2) a quadrivalent vaccine, which in addition to HPV-16
and HPV-18 also covers HPV-6 and HPV-11; and
Several tests have been approved by the FDA for the
3) a 9-valent vaccine approved in 2014, which covers
detection of cervical HPV. They assess exfoliated cervi-
an additional five high-risk HPV genotypes. The bivalent
cal cells for the presence of subsets of the 15–18 poten-
and quadrivalent vaccines offer limited cross-protection
tially cancer-causing (high-risk) HPV genotypes (59).
against approximately 30% of cases of cervical cancer
Most test for 13–14 of the most common high-risk geno-
caused by HPV genotypes other than HPV-16 and HPV-18
types. These test kits should be used according to their
(20, 64). The 9-valent vaccine covers approximately
FDA-approved labeling, be validated, and meet specific
20% more high-risk HPV infections caused by the five
criteria for clinical performance (60–62). Liquid-based
additional HPV genotypes (65). The Advisory Commit-
cytology and HPV tests are FDA approved for use with
specific sample collection media. Only FDA-approved tee on Immunization Practices (ACIP) of the Centers
media should be used for HPV tests because unapproved for Disease Control and Prevention and the American
media may provide false results under certain conditions. College of Obstetricians and Gynecologists recommend
The indications for HPV testing include the following: administration of the vaccine to females aged 9–26 years
(66, 67). The Panel on Opportunistic Infections in HIV-
• Determination of the need for colposcopy in women Infected Adults and Adolescents recommends vaccin-
with an ASC-US cytology result (“reflex testing”) ating HIV-infected females aged 9–26 years (68). The
• Use as an adjunct to cytology for cervical cancer Panel and ACIP advocate vaccinating girls before they
screening in women aged 30–65 years and older reach an age at which they may be exposed to HPV.
(“cotesting”) However, many women will receive the vaccine when
• One HPV test was FDA approved in 2014 for pri- they are older and after viral exposure. It is predicted that
mary cervical cancer screening in women 25 years significant reduction in the number of cases of cervical
and older cancer likely will not begin until approximately 20 years
after widespread vaccination (69). At this time, cervical
Testing should be performed only to detect the pres- cancer screening remains the best approach to protect
ence of high-risk HPV. There is no role for testing for women from cervical cancer, and screening recommenda-
low-risk genotypes, and tests for low-risk HPV should tions apply regardless of HPV vaccination status (6).
not be performed (40). All references to HPV testing in Revaccination with the 9-valent HPV vaccine in
this document are to testing for high-risk HPV. Major individuals who previously completed the three-dose
society guidelines include some off-label uses, such series with the bivalent HPV vaccine or the quadrivalent
as follow-up after treatment. Off-label use should be HPV vaccine currently is not a routine recommendation
restricted to those indications described in major society, (67). If the HPV vaccination series already has been ini-
peer-reviewed guidelines (6, 40). tiated in a female patient, the series may be completed
with any HPV vaccine product (66). Thus, given the
Human Papillomavirus Genotyping high degree of protection with any HPV vaccine and the
There are commercially available, FDA-approved HPV risk of viral infection in unvaccinated women, eligible
genotyping tests for HPV-16, HPV-18, or the two in patients should be vaccinated with whichever vaccine is
combination. Guidelines support the use of HPV geno- readily available to them, and vaccination should not be
typing for women aged 30–65 years who are undergoing delayed to obtain a specific vaccine type.
cotesting and have negative Pap test results but positive
high-risk HPV test results (40). Balancing Benefits and Risks in
Cervical Cancer Prevention
Human Papillomavirus Vaccination Protection from cervical cancer is the primary goal of
The introduction of vaccines targeting the most com- screening, but as the prevalence of the disease decreases,
mon cancer-causing HPV genotypes has advanced the other considerations may become equally important in
primary prevention of cervical cancer. In Australia, the decision-making process. For example, the effects
which has a population-based vaccination program of invasive diagnostic workups (eg, colposcopy and
with high adherence, a decrease in high-grade cervical biopsy) and overtreatment of lesions likely to regress
abnormalities was noted within 3 years after program have adverse consequences related to costs and poten-
implementation (63). The FDA has approved three vac- tially to reproductive outcomes. In addition, the anxiety

Practice Bul­le­tin No. 168 5

and stigma associated with HPV infection are significant neoplastic changes (23, 32, 33, 35–38). Although can-
concerns for women who participate in cervical cancer cer is rare in adolescents, neoplasia is not. In a report
screening programs (70–72). of 10,090 Pap test results in females aged 12–18 years,
Cervical cancer screening guidelines have been 422 specimens (5.7%) were reported as LSIL and only
revised several times in the past decade, and the differ- 55 specimens (0.7%) were HSIL (80).
ences in the lifetime risk of cervical cancer are small Earlier onset of screening than recommended may
across these screening strategies. Because most cervical increase anxiety, morbidity, and expense and lead to
cancer detected through screening is found in the early overuse of follow-up procedures. The emotional effect
stages, life expectancy differences are even smaller of labeling an adolescent with a sexually transmitted
because survival is high (1). The recent revisions have infection and potential precancer must be considered
balanced cancer detection with harms of screening by because adolescence is a time of heightened concern
incorporating the powerful negative predictive value of for self-image and emerging sexuality. Studies have
HPV testing and lengthening screening intervals. Current documented a significant increase in rates of preterm
guidelines are based on achieving the benchmark cancer birth among women previously treated with excisional
risk that would be achieved by performing cervical cytol- procedures for neoplasia (81). However, in one system-
ogy every 3 years. Lower risks of cancer are achievable atic review and meta-analysis, this increased risk was
with more frequent screening but would require more observed only when women who underwent such pro-
diagnostic evaluations, patient inconvenience, cost, and cedures were compared with women with no history of
other harms of screening. The screening interval with the abnormal cervical cytology or colposcopy results (82).
appropriate balance between benefits and harms is cur- Avoiding unnecessary excision or ablation of the cervix
rently a matter of active discussion (73). Incorporating a in young women clearly is advisable, even though the
discussion of the benefits as well as the potential harms association between loop electrosurgical excision proce-
of screening into patient conversations will help to dure and preterm birth has been challenged (83).
inform clinical decision making and allow for inclusion Initiation of reproductive health care should not be
of the patient’s preferences in the process. predicated on cervical cancer screening (84). Important
strategies for preventing cervical cancer in women
younger than 21 years include HPV vaccination and
Clinical Considerations and counseling about safe-sex practices to limit exposure to
sexually transmitted infections.
Recommendations
What tests should be performed for screening?
When should screening begin?
Women aged 21–29 years should be tested with cervical
Cervical cancer screening should begin at age 21 years. cytology alone, and screening should be performed every
With the exception of women who are infected with HIV 3 years. Cotesting should not be performed in women
or who are otherwise immunocompromised, women younger than 30 years. For women aged 30–65 years,
younger than 21 years should not be screened regardless cotesting with cytology and HPV testing every 5 years is
of the age of sexual initiation or the presence of other preferred; screening with cytology alone every 3 years
behavior-related risk factors (Table 1) (6). The recom- is acceptable. Liquid-based and conventional methods of
mendation to start screening at age 21 years regardless of cervical cytology collection are acceptable for screening
the age of onset of sexual intercourse is based on the very (6). These screening recommendations are not meant
low incidence of cancer and the lack of data that screen- for women with cervical cancer or those who have HIV
ing is effective in this age group (74, 75). Only 0.1% of infection, are immunocompromised, or were exposed to
cases of cervical cancer occur before age 20 years (1), diethylstilbestrol in utero. Since the publication of the
which translates to approximately 1–2 cases per year per 2011 joint ACS, ASCCP, and ASCP guidelines and the
1,000,000 females aged 15–19 years (1, 76). Further, USPSTF guidelines, a test for primary HPV testing has
studies from the United States and the United Kingdom been approved by the FDA and is discussed separately
have demonstrated that screening younger women has (see “What is the role for cervical cancer screening with
not decreased their rate of cervical cancer (74, 77). HPV testing alone?”).
Human papillomavirus infection is commonly Human papillomavirus testing is more sensitive
acquired by young women shortly after the initiation but less specific than cervical cytology (85). In the
of vaginal intercourse (30, 31, 33, 34, 77, 78) and other 2011 joint ACS, ASCCP, and ASCP guidelines and the
sexual activity (79). Nearly all cases are cleared by the USPSTF guidelines, cotesting is not recommended for
immune system within 1–2 years without producing women younger than 30 years because of the very high

6 Practice Bulletin No. 168

Table 1. Screening Methods for Cervical Cancer for the General Population: Joint Recommendations of the American Cancer
Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology* ^
Population Recommended Screening Method Comment
Women younger than 21 years No screening  
Women aged 21–29 years Cytology alone every 3 years  
Women aged 30–65 years Human papillomavirus and cytology cotesting Screening by HPV testing alone is not recommended*
(preferred) every 5 years
Cytology alone (acceptable) every 3 years
Women older than 65 years No screening is necessary after adequate Women with a history of CIN 2, CIN 3, or
negative prior screening results adenocarcinoma in situ should continue routine
age-based screening for a total of 20 years after
spontaneous regression or appropriate management
of CIN 2, CIN 3, or adenocarcinoma in situ
Women who underwent total No screening is necessary Applies to women without a cervix and without a
hysterectomy history of CIN 2, CIN 3, adenocarcinoma in situ, or
cancer in the past 20 years
Women vaccinated against HPV Follow age-specific recommendations
(same as unvaccinated women)  
Abbreviations: CIN, cervical intraepithelial neoplasia; HPV, human papillomavirus.
*After the Joint Recommendations were published, a test for screening with HPV testing alone was approved by the U.S. Food and Drug Administration. Gynecologic care
providers using this test should follow the interim guidance developed by the American Society for Colposcopy and Cervical Pathology and the Society for Gynecologic
Oncology (Huh WK, Ault KA, Chelmow D, Davey DD, Goulart RA, Garcia FA, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening:
interim clinical guidance. Obstet Gynecol 2015;125:330–7.).
Modified from Saslow D, Solomon D, Lawson HW, Killackey M, Kulasingam SL, Cain J, 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. ACS-ASCCP-ASCP Cervical Cancer
Guideline Committee. CA Cancer J Clin 2012;62:147–72.

prevalence of high-risk HPV infections and the low inci- a statistically significant reduction of CIN 3 or cancer
dence of cervical cancer in sexually active women in this detection in the second round of screening, and a second
age group (6, 86). Use of cotesting in women younger study demonstrated a statistically significant reduction
than 30 years largely would detect transient HPV infec- from 0.03% to 0% in the second phase of screening (90,
tion without carcinogenic potential. In women younger 91). The difference in the rate of cancer detection was
than 30 years, the increased sensitivity and decreased not reported in the third trial (92).
specificity of cotesting would result in more testing than Cytology alone has been much less effective for
would cytology screening alone, without an appreciable the detection of adenocarcinoma of the cervix than
decrease in cancer incidence (87). for the detection of squamous cancer (93). Cotesting has
Women aged 30 years and older with a negative the additional advantage of better detection of adenocar-
cervical cytology screening result and a negative high- cinoma of the cervix and its precursors than cytology
risk HPV test result have been shown to be at extremely screening alone (94, 95).
low risk of developing CIN 2 or CIN 3 during the next It is important to educate patients about the nature of
4–6 years (88). This risk was much lower than the risk cervical cancer screening, its limitations, and the ratio-
for women who had only a negative cytology test result nale for prolonging the screening interval. Regardless
(85). In the Kaiser Permanente Northern California of the frequency of cervical cancer screening, patients
cohort, the 5-year risk of CIN 3+ was 0.26 in women should be counseled that annual well-woman visits are
with negative cytology alone and 0.08 in women with a recommended even if cervical cancer screening is not
negative cotest result (89). performed at each visit (96).
Three randomized trials have compared cotest-
ing with cytology screening alone in women aged What is the optimal frequency of cervical
30–65 years (90–92). Each of the trials had a com- cytology screening for women aged
plex protocol and differed in the way that women with 21–29 years?
HPV-positive test results were evaluated. In each trial,
cotesting detected an increased proportion of high-grade Few studies have been performed that specifically
dysplasia in the first round of screening and a low rate of address the interval for screening women aged 21–29
cancer with subsequent testing with cytology screening years. A modeling study that examined outcomes for
alone in the second round. The first trial demonstrated women aged 20 years and screened over a 10-year

Practice Bul­le­tin No. 168 7

period predicted that the number of colposcopy pro- in women with a negative result from cytology testing
cedures would be reduced by approximately one half alone, and the 5-year risk was 0.08 in women with a
(187 per 1,000 women versus 403 per 1,000 women) if negative cotest result (89). The Agency for Healthcare
these women were screened every 3 years rather than Research and Quality has performed modeling studies
annually, with marginal difference in lifetime cancer risk of cases of cancer, deaths, and harms (as measured by
(0.69% versus 0.33%) (70). These results are similar to colposcopy) (97). In three separate models over a wide
those reported in a study that compared outcomes associ- range of assumptions, cotesting every 5 years compared
ated with screening every 1 year, 2 years, or 3 years (97). with cytology screening alone every 3 years was associ-
Compared with screening every 3 years, screening every ated with a similar number of or fewer cases of cancer
2 years was associated with negligible change in risk of (6.23–7.39 versus 5.98–8.97 per 1,000 women over a
cancer (37 cases per 100,000 women versus 39 cases lifetime), number of deaths related to cancer (1.10–1.35
per 100,000 women) and more colposcopy procedures versus 0.95–1.55 per 1,000 women over a lifetime),
(176 procedures per 100,000 women versus 134 pro- and number of colposcopy procedures (626–907 versus
cedures per 100,000 women). A U.K. study noted no 416–1,090 per 1,000 women over a lifetime).
difference in risk between women aged 20–39 years Cytology screening alone is an acceptable alterna-
with cervical cancer who had been screened 2 years or tive to cotesting and can be continued every 3 years until
3 years after their last negative test result (98). Annual age 65 years. Studies over the past several decades have
screening leads to a very small increase in cases of shown that in an organized program of cervical cancer
cancer prevented at the cost of a very large excess of screening, annual cytology examinations offer no net
procedures and treatments and should not be performed. advantage over screening performed at 2-year or 3-year
Because 2-year and 3-year testing intervals appear to intervals (98–101). As in younger women, modeling
be associated with similar reductions in risk of cancer, studies showed that 1-year and 3-year screening intervals
and a 3-year testing interval requires less additional test- yielded low cervical cancer rates (70, 97). Cancer rates
ing, screening should be performed every 3 years in the with a screening interval of every 3 years were slightly
21–29-year age group. Annual screening should not be higher but were achieved with far fewer colposcopy
performed. procedures. Decision analyses demonstrate that screen-
ing every 3 years with cytology alone or screening every
What is the optimal frequency of cervical 5 years with cotesting provides a reasonable balance
cytology screening for women aged between the benefits and burdens of screening (97). The
30–65 years? consensus conference review for the ACS, ASCCP, and
the ASCP cervical cancer screening guidelines found
In women aged 30–65 years, cotesting with cervical inadequate high-quality data to recommend altering the
cytology screening and HPV testing is preferred and screening interval based on prior negative cytology results
should be performed every 5 years. If screening is per- in any age group (6). A matched case–control study cal-
formed with cervical cytology alone, it can be done with culated the risk of invasive cancer at different screening
either conventional or liquid-based cytology collection intervals and reported that the risk was not altered by a
methods and should be performed every 3 years. Annual history of a prior abnormal cytology result or the number
screening should not be performed. of previous normal screening test results (102).
The increased sensitivity of cotesting compared with
cytology screening alone allows for greater detection of At what age is it appropriate to discontinue
CIN 3 (6, 88). However, the decreased specificity results screening?
in the need for more follow-up testing. The decrease in
cancer incidence achieved by 3-year cytology screening Screening by any modality should be discontinued
alone is the standard of care and considered acceptable. after age 65 years in women with evidence of adequate
Using this as a benchmark, performing cotesting every negative prior screening test results and no history of
5 years achieves slightly lower rates of cancer, with less CIN 2 or higher. Adequate negative prior screening test
screening and fewer follow-up colposcopy procedures. results are defined as three consecutive negative cytol-
A pooled analysis of seven European studies reported a ogy results or two consecutive negative cotest results
0.28% risk of CIN 3 or cancer 6 years after a negative within the previous 10 years, with the most recent test
cotesting result compared with a 0.51% risk of CIN 3 performed within the past 5 years. Women with a history
or cancer 3 years after a negative result from cytology of CIN 2, CIN 3, or adenocarcinoma in situ should con-
testing alone (88). In the Kaiser Permanente Northern tinue screening for a total of 20 years after spontaneous
California cohort, the 3-year risk of CIN 3+ was 0.16 regression or appropriate management of CIN 2, CIN 3,

8 Practice Bulletin No. 168

or adenocarcinoma in situ, even if it extends screening result, and 0.12% had vaginal intraepithelial neoplasia
past age 65 years. on biopsy. No cases of cancer were reported. Continued
Women aged 65 years and older do get cervical vaginal cytology examinations in this population of
cancer. Women in this age group represent 14.1% of women are not effective, particularly because of the very
the U.S. female population but have 19.6% of the new low risk of developing vaginal cancer, and will cause
cases of cervical cancer (1, 103). However, as in younger inconvenience, anxiety, and overtreatment.
women, most cases of cervical cancer occur in Women who had high-grade cervical intraepithelial
unscreened or inadequately screened women (104). lesions before hysterectomy with removal of the cervix
Because cervical cancer occurs a median of can develop recurrent intraepithelial neoplasia or carci-
15–25 years after HPV infection, screening women in noma at the vaginal cuff years after the procedure (107,
this age group would prevent very few cases of cancer. 108). In a systematic review, in a group of women with
Modeling studies suggest that, in women screened with prior CIN 3, abnormal cytology results were reported
cytology every 3 years until age 65 years, continued in 14.1% of cases, but vaginal intraepithelial neoplasia
screening every 3 years until age 90 years in 1,000 on biopsy was rare (1.7%), and only one case of cancer
women would prevent approximately 1.6 cases of can- was reported, which was diagnosed 3 years after hyster-
cer and 0.5 cancer-related deaths (97). This slight gain ectomy (106). Women should continue to be screened if
would come at significant cost, including an increase in they have had a total hysterectomy and have a history of
required colposcopy procedures. Given the low risk of CIN 2 or higher in the past 20 years or cervical cancer
progression to cancer in women in this age group with at any point. The role of HPV testing has not been clari-
newly acquired infection, there is no need to resume fied in this population. Continued screening for 20 years
screening, even if a woman has a new sexual partner. is recommended in women who still have a cervix and
To further complicate screening in this age group, a history of CIN 2 or higher (40). Therefore, screening
epithelial atrophy, common after menopause, likely pre- with cytology alone every 3 years for 20 years after the
disposes women to false-positive cytology screening test initial posttreatment surveillance period seems to be rea-
results. One study noted an extremely low positive pre- sonable for these women.
dictive value of abnormal cervical cytology test results
when performed in postmenopausal women (105). Most What is the role for cervical cancer screening
positive Pap test results were false positives and likely with HPV testing alone?
would be followed with additional procedures, anxiety,
In April 2014, the FDA modified the labeling of a cur-
and expense.
rently marketed HPV test to include the additional
When is it appropriate to discontinue screen- indication of primary cervical cancer screening (HPV
ing for women who have had a total primary screening) (109). Primary HPV screening was
explicitly not recommended at the time of the 2011 joint
hysterectomy?
ACS, ASCCP, and ASCP guidelines. This recommenda-
In women who have had a hysterectomy with removal tion was based on concerns about the poor specificity
of the cervix (total hysterectomy) and have never had of HPV testing, the lack of a proven triage algorithm to
CIN 2 or higher, routine cytology screening and HPV determine which patients with positive tests required
testing should be discontinued and not restarted for any diagnostic evaluations, and the potential for excess diag-
reason. nostic evaluations and treatments. Since that time, a large
Primary vaginal cancer is the rarest of the gyneco- U.S.-based study of HPV primary screening, known as
logic malignancies (2). Women who have had a total the Addressing the Need for Advanced HPV Diagnostics
hysterectomy and have no history of CIN 2 or higher are trial, was conducted and validated an effective triage algo-
at very low risk of developing vaginal cancer. Cytology rithm (110). In the trial, positive specimens underwent
screening in this group has a small chance of detecting HPV genotyping. If a specimen was positive for HPV-16
an abnormality, and the test has a very low positive or HPV-18, colposcopy was performed. If a specimen
predictive value. A systematic review aggregated data was negative for HPV-16 and HPV-18, cytology testing
from 19 studies that involved 6,543 women who had a was performed on the specimen, and if the results were
hysterectomy in which the cervix was not affected by abnormal, colposcopy was performed. If cytology results
CIN and 5,037 women who had a hysterectomy in which were normal, repeat cotesting was performed in 1 year.
the cervix was affected by CIN 3 (106). On follow-up, Based on the HPV test’s equivalent or superior
among the women with hysterectomy who did not have effectiveness for primary cervical cancer screening
CIN, 1.8% had an abnormal vaginal cytology screening compared with cytology alone in the Addressing the Need

Practice Bul­le­tin No. 168 9

for Advanced HPV Diagnostics trial, the FDA modi- screening histories. The primary HPV screening test
fied the labeling of the test to include an indication for should not be used in women who no longer have a
its use for primary screening in women starting at age cervix. Which test to perform at 1-year follow-up in
25 years. Cytology alone and cotesting remain the options women with positive HPV primary screening test results
specifically recommended in current major society guide- and negative genotyping and cytology test results is not
lines. In 2015, ASCCP and SGO published interim stated, but cotesting is reasonable. There is no guid-
guidance for the use of the FDA-approved HPV test for ance for use of the test in women with HIV or who are
primary cervical cancer screening (8). The interim guid- immunocompromised. Only one specific HPV test has
ance panel concluded that because of its equivalent or FDA approval for primary screening (109). No other
superior effectiveness, in women 25 years and older, the tests have undergone validation. If primary screening
FDA-approved primary HPV screening test can be con- is performed, it should be done with the approved test.
sidered as an alternative to current cytology-based cervical
cancer screening methods (8). How should ASC-US cytology and negative
If screening with primary HPV testing is used, it HPV test results be managed?
should be performed as per the ASCCP and SGO interim
guidance (8), which clarifies a number of important Women with ASC-US cytology and negative HPV test
issues not specified in the product labeling. The test results, whether from reflex HPV testing or cotesting,
should not be used in women younger than 25 years; have a low risk of CIN 3, but it is slightly higher than
these women should continue to be screened with cytol- the risk in women with a negative cotest result, and it is
ogy alone. Rescreening after a negative primary HPV recommended that they have cotesting in 3 years (40,
screening result should occur no sooner than every 111) (Table 2). This recommendation is a change from
3 years. Positive test results should be triaged with geno- the 2011 joint ACS, ASCCP, and ASCP cervical cytol-
typing for HPV-16 and HPV-18, and if the genotyping ogy screening guidelines, which recommended routine
test results are negative, with cytology testing. If geno- screening for these women (6).
typing and cytology test results are negative, patients The management of ASC-US has been associated
should have follow-up testing in 1 year. with much confusion. Frequently, it has been managed
Although not explicitly stated in the interim guid- as if it is a diagnosis, but it actually represents diagnostic
ance, several other points are important. Screening uncertainty, comprising a mix of patients who have
should stop at age 65 years in women with negative squamous intraepithelial lesions and others who do not.

Table 2. Management of Cervical Cancer Screening Results ^

Screening Method Result Management
Cytology screening alone Cytology negative Screen again in 3 years
ASC-US cytology and reflex HPV negative Cotest in 3 years
All others Refer to ASCCP guidelines*
Cotesting Cytology negative, HPV negative Screen again in 5 years
ASC-US cytology, HPV negative Screen again in 3 years
Cytology negative, HPV positive Option 1: 12-month follow-up with cotesting
Option 2: Test for HPV-16 or HPV-18 genotypes
• If positive results from test for HPV-16 or HPV-18,
referral for colposcopy
• If negative results from test for HPV-16 and
HPV-18, 12-month follow-up with cotesting
All others Refer to ASCCP guidelines*
Abbreviations: ASCCP, American Society for Colposcopy and Cervical Pathology; ASC-US, atypical squamous cells of undetermined significance; HPV, human
papillomavirus.
*Massad LS, Einstein MH, Huh WK, Katki HA, Kinney WK, Schiffman M, et al, for the 2012 ASCCP Consensus Guidelines Conference. 2012 Updated Consensus Guidelines
for the Management of Abnormal Cervical Cancer Screening Tests and Cancer Precursors. J Low Genit Tract Dis 2013;17:S1–S27.
Modified from Saslow D, Solomon D, Lawson HW, Killackey M, Kulasingam SL, Cain J, 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. ACS-ASCCP-ASCP Cervical Cancer
Guideline Committee. CA Cancer J Clin 2012;62:147–72, with additional modifications based on Massad LS, Einstein MH, Huh WK, Katki HA, Kinney WK, Schiffman M,
et al, for the 2012 ASCCP Consensus Guidelines Conference. 2012 Updated Consensus Guidelines for the Management of Abnormal Cervical Cancer Screening Tests
and Cancer Precursors. J Low Genit Tract Dis 2013;17:S1–S27.

10 Practice Bulletin No. 168

Human papillomavirus testing is a very effective method group. A summary of 11 prospective studies with
of triage for an ASC-US cytology result. With a nega- 1–16-year follow-up noted a 12-month risk of CIN 3
tive HPV test result, the risk of a precancerous lesion of 0.8–4.1% (6). In the Kaiser Permanente Northern
is extremely low. In the Kaiser Permanente Northern California cohort, 5-year risks of CIN 3+ and cancer
California cohort, 5-year risks of CIN 3+ and cancer in were 4.5% and 0.34%, respectively (112). This low risk
women aged 30–64 years with ASC-US cytology and a of a premalignant lesion makes colposcopy a poor diag-
negative HPV test result were 0.43% and 0.05%, respec- nostic option for this population.
tively, which is significantly higher than the 5-year Cytology-negative, HPV-positive cotest results in
risks for women with negative cotest results (0.08% and women who are 30 years and older should be managed
0.011%, respectively) (112). The risk of CIN 3+ actually in one of two ways (Fig. 1):
was comparable to the risk among women with negative 1. Repeat cotesting in 12 months. If the repeat cervi-
cytology test results alone; therefore (using the principle cal cytology test result is ASC-US or higher or the
of managing test results with similar risk in the same HPV test result is still positive, the patient should
way), the 2012 ASCCP Consensus Guidelines for the be referred for colposcopy. Otherwise, the patient
Management of Abnormal Cervical Cancer Screening should have cotesting in 3 years. The level of cyto-
Tests and Cancer Precursors (40) recommend that logy at which a diagnostic evaluation should be per-
women aged 30–65 years should have follow-up cotest- formed changed from the previously recommended
ing in 3 years rather than in 5 years, as originally recom- LSIL to any abnormality (ASC-US or higher) with the
mended in the 2011 screening guidelines (6). If their 2012 ASCCP revised guidelines for management of
3-year cotest results are negative, they then can return to abnormal cervical cancer screening test results (40).
age-appropriate routine screening (40, 111).
2. Immediate HPV genotype-specific testing for
How should cytology-negative, HPV-positive HPV-16 and HPV-18 can be performed. Women
cotest results be managed? with positive test results for either HPV genotype
should be referred directly for colposcopy. Women
In a recent study, cytology-negative and HPV-positive with negative test results for both HPV genotypes
cotest results occurred in 3.7% of women older than should be cotested in 12 months, with management
30 years (94). Counseling and management of women of results as described in the 2012 ASCCP revised
with these results is a significant issue with cotest- guidelines for the management of abnormal cervical
ing. The risk of significant pathology is small in this cancer screening test results (40, 111).

Figure 1. Management of women 30 years and older, who are cytology negative, but HPV positive. Abbreviations: ASC, atypical squa-
mous cells; ASCCP, American Society for Colposcopy and Cervical Pathology; HPV, human papillomavirus. (Reprinted from Massad LS,
Einstein MH, Huh WK, Katki HA, Kinney WK, Schiffman M, et al, for the 2012 ASCCP Consensus Guidelines Conference. 2012 Updated
Consensus Guidelines for the Management of Abnormal Cervical Cancer Screening Tests and Cancer Precursors. J Low Genit Tract Dis
2013;17:S1–S27.) ^

Practice Bul­le­tin No. 168 11

 No studies directly compare different management in the vaccine are expected to continue to occur (115,
options for women with HPV-positive and cytology- 116). The 9-valent HPV vaccine immunizes against five
negative test results. The rationale for repeat cotesting additional high-risk subtypes but still does not cover all
comes from results of cohort studies, which show that subtypes. Current recommendations from ACIP and the
most transient infections clear by 12 months. A cohort American College of Obstetricians and Gynecologists
study reported that in 60% of women with HPV-positive, allow for vaccination through age 26 years, a time when
liquid-based, cytology-negative test results, the infection many women may already have acquired the virus,
was cleared in a median of 6 months (25). A separate which significantly decreases the efficacy of the vaccine
cohort study reported that in 67% of patients, the HPV (66, 67). The rate of vaccine administration is far from
infection was cleared by 1 year (29). Of women who 100%, and given the absence of a vaccine registry in the
had infections that persisted at 1 year, 21% developed United States, it often is difficult to ascertain who has
CIN 2 or higher within 30 months. In the Kaiser been vaccinated or who has received all three doses of
Permanente Northern California cohort, 47% of women the vaccine (117, 118). Long-term efficacy of the vac-
remained HPV positive at 1 year. At the time of repeat cine remains incompletely established. Although HPV
testing, any abnormal cotest result was associated with vaccination is an important step toward cervical cancer
higher risk than the same abnormality at baseline (112). prevention, it does not remove the need for routine cervi-
Repeat cotesting in 1 year allows most women with tran- cal cancer screening.
sient infection and no carcinogenic risk sufficient time for
the HPV infection to clear and identifies a smaller group Are any alternative cervical cancer screening
at higher risk of precancerous lesions to undergo colpos- strategies recommended for specific
copy. The higher risks noted in the Kaiser cohort justify populations?
colposcopy for any abnormality at this point and 3-year
follow-up in patients whose cotest result has returned to Certain risk factors have been associated with CIN in
observational studies. Women with any of the following
normal.
risk factors may require more frequent cervical cancer
The FDA-approved HPV tests may be used to
screening than recommended in the routine screen-
determine if a woman with a positive cotest result for
ing guidelines, which were intended for average-risk
HPV has HPV-16 or HPV-18. If HPV-16 or HPV-18
women:
is detected, the risk of CIN 3 approaches 10% within
a few years, a risk high enough to justify colposcopy • Women who are infected with HIV
(18, 113, 114). These tests may be used as an alterna- • Women who are immunocompromised (such as
tive in patients with HPV-positive, cytology-negative those who have received solid organ transplants)
cotest results, and if positive, the patient is referred for
• Women who were exposed to diethylstilbestrol in
immediate colposcopy. If results are negative, cotesting
utero
is repeated in 1 year because some risk from other geno-
types still exists, and results are managed as indicated in • Women previously treated for CIN 2, CIN 3, or
Figure 1 (40). cancer
The Panel on Opportunistic Infections in HIV-
Should administration of the HPV vaccine Infected Adults and Adolescents recommends that
change how cervical cancer screening is women who are infected with HIV should have age-
performed? based cervical cancer screening as follows (68). For
more information, see Practice Bulletin No. 167,
Women who have received the HPV vaccine should be Gynecologic Care for Women and Adolescents With
screened according to the same guidelines as women Human Immunodeficiency Virus.
who have not been vaccinated. The bivalent and quadri-
valent HPV vaccines immunize against only two of the • Initiation of cervical cancer screening with cytology
carcinogenic genotypes, HPV-16 and HPV-18. These alone should begin within 1 year of onset of sexual
two genotypes are responsible for up to approximately activity or, if already sexually active, within the first
75% of all cases of cervical cancer. However, despite year after HIV diagnosis but no later than 21 years
data suggesting that the HPV vaccine provides nearly of age.
100% protection against CIN caused by these two geno- • Cervical cancer screening in women who are
types in previously uninfected women, 30% of cases of infected with HIV should continue throughout a
cervical cancer from other HPV genotypes not included woman’s lifetime (ie, not stopping at age 65 years).

12 Practice Bulletin No. 168

 • In women infected with HIV who are younger than least 20 years after treatment. A meta-analysis demon-
30 years, if the initial cytology screening result is strated that women with a history of treatment for CIN 2
normal, the next cytology screening should be in or higher remain at a 2.8-fold increased risk of invasive
12 months. If the results of three consecutive annual disease for up to 20 years after treatment (119). Because
cervical cytology screenings are normal, follow- of this increased risk, women with a history of CIN 2
up cervical cytology screening should be every or higher should continue to undergo routine age-based
3 years. Cotesting is not recommended for HIV- screening for 20 years after the initial posttreatment
infected women younger than 30 years. surveillance period, even if it requires that screening
• Women infected with HIV who are 30 years and continue past age 65 years (6, 40).
older can be screened with cytology alone or cotest-
ing. After women screened with cytology alone
have had three consecutive annual test results Summary of
that are normal, follow-up screening can be every
3 years. Women infected with HIV who have one
Recommendations and
negative cotest result (normal cytology and HPV Conclusions
negative) can have their next cervical cancer screen- The following recommendations and conclusions
ing in 3 years. are based on good and consistent scientific evi-
• In women with HIV infection, cotesting results that dence (Level A):
are cytology negative but HPV positive are man-
aged as in the general population (see “How should Cervical cancer screening should begin at age
cytology-negative, HPV-positive cotest results be 21 years. With the exception of women who are
infected with HIV or who are otherwise immuno-
managed?”).
compromised, women younger than 21 years should
• Women with HIV infection who have cervical not be screened regardless of the age of sexual ini-
cytology results of LSIL or worse should be referred tiation or the presence of other behavior-related risk
for colposcopy. factors.
• For women with HIV infection who are 21 years Women aged 21–29 years should be tested with
or older and have ASC-US test results, if reflex cervical cytology alone, and screening should be
HPV testing results are positive, referral to col- performed every 3 years. Cotesting should not be
poscopy is recommended. If HPV testing is not performed in women younger than 30 years. Annual
available, repeat cervical cytology in 6–12 months screening should not be performed.
is recommended, and for any result of ASC-US For women aged 30–65 years, cotesting with cytol-
or worse on repeat cytology, referral to colpos- ogy and HPV testing every 5 years is preferred;
copy is recommended. Repeat cytology in 6–12 screening with cytology alone every 3 years is accept-
months, but not HPV testing, is recommended for able. Annual screening should not be performed.
HIV-infected women younger than 21 years with
Liquid-based and conventional methods of cervical
ASC-US test results. Although not explicitly stated cytology collection are acceptable for screening.
in the Panel guidelines, women with HIV infection
who have ASC-US, HPV-negative results (whether Screening by any modality should be discontinued
after age 65 years in women with evidence of ade-
from reflex HPV testing or cotesting) can return to
quate negative prior screening test results and no
regular screening.
history of CIN 2 or higher. Adequate negative prior
No studies or major society recommendations exist screening test results are defined as three consecu-
to guide cervical cancer screening in women who tive negative cytology results or two consecutive
are immunocompromised because of non-HIV causes. negative cotest results within the previous 10 years,
Annual cytology traditionally has been performed in with the most recent test performed within the past
these women, but it is reasonable to extrapolate the 5 years.
recommendations for women with HIV infection to this In women who have had a hysterectomy with
group. Annual cervical cytology screening is reasonable removal of the cervix (total hysterectomy) and have
for women exposed to diethylstilbestrol in utero. never had CIN 2 or higher, routine cytology screen-
Women treated in the past for CIN 2 or higher ing and HPV testing should be discontinued and not
remain at risk of persistent or recurrent disease for at restarted for any reason.

Practice Bul­le­tin No. 168 13

 Women with any of the following risk factors may with positive test results for either HPV geno-
require more frequent cervical cancer screening type should be referred directly for colposcopy.
than recommended in the routine screening guide- Women with negative test results for both HPV
lines, which were intended for average-risk women: genotypes should be cotested in 12 months, with
management of results as described in the 2012
—Women who are infected with HIV ASCCP revised guidelines for the management
—Women who are immunocompromised (such as of abnormal cervical cancer screening test results.
those who have received solid organ transplants)
—Women who were exposed to diethylstilbestrol The following recommendation is based primarily
in utero on consensus and expert opinion (Level C):
—Women previously treated for CIN 2, CIN 3, or Women who have received the HPV vaccine should
cancer be screened according to the same guidelines as
women who have not been vaccinated.
The following recommendations are based on lim-
ited and inconsistent scientific evidence (Level B):
Women with a history of CIN 2, CIN 3, or adeno-
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Practice Bul­le­tin No. 168 19

 Copyright October 2016 by the American College of Ob­ste­tri­
The MEDLINE database, the Cochrane Library, and the cians and Gynecologists. All rights reserved. No part of this
American College of Obstetricians and Gynecologists’ publication may be reproduced, stored in a re­triev­al sys­tem,
own internal resources and documents were used to con­ posted on the Internet, or transmitted, in any form or by any
duct a lit­er­a­ture search to lo­cate rel­e­vant ar­ti­cles pub­lished means, elec­tron­ic, me­chan­i­cal, photocopying, recording, or
be­ tween January 1990–January 2015. The search was oth­er­wise, without prior written permission from the publisher.
re­strict­ed to ar­ ti­
cles pub­ lished in the English lan­ guage.
Pri­or­i­ty was given to articles re­port­ing results of orig­i­nal Requests for authorization to make photocopies should be
re­search, although re­view ar­ti­cles and com­men­tar­ies also directed to Copyright Clearance Center, 222 Rosewood Drive,
were consulted. Ab­stracts of re­search pre­sent­ed at sym­po­ Danvers, MA 01923, (978) 750-8400.
sia and sci­en­tif­ic con­fer­enc­es were not con­sid­ered adequate ISSN 1099-3630
for in­clu­sion in this doc­u­ment. Guide­lines pub­lished by The American College of Obstetricians and Gynecologists
or­ga­ni­za­tions or in­sti­tu­tions such as the Na­tion­al In­sti­tutes 409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920
of Health and the Amer­i­can Col­lege of Ob­ste­tri­cians and
Gy­ne­col­o­gists were re­viewed, and ad­di­tion­al studies were Cervical cancer screening and prevention. Practice Bulletin No. 168.
located by re­view­ing bib­liographies of identified articles. American College of Obstetricians and Gynecologists. Obstet Gynecol
When re­li­able research was not available, expert opinions 2016;128:e111–30.
from ob­ste­tri­cian–gynecologists were used.
Studies were reviewed and evaluated for qual­i­ty ac­cord­ing
to the method outlined by the U.S. Pre­ven­tive Services
Task Force:
I Evidence obtained from at least one prop­ er­
ly
de­signed randomized controlled trial.
II-1 Evidence obtained from well-designed con­ trolled
tri­als without randomization.
II-2 Evidence obtained from well-designed co­ hort or
case–control analytic studies, pref­er­a­bly from more
than one center or research group.
II-3 Evidence obtained from multiple time series with or
with­out the intervention. Dra­mat­ic re­sults in un­con­
trolled ex­per­i­ments also could be regarded as this
type of ev­i­dence.
III Opinions of respected authorities, based on clin­i­cal
ex­pe­ri­ence, descriptive stud­ies, or re­ports of ex­pert
committees.
Based on the highest level of evidence found in the data,
recommendations are provided and grad­ed ac­cord­ing to the
following categories:
Level A—Recommendations are based on good and con­
sis­tent sci­en­tif­ic evidence.
Level B—Recommendations are based on limited or in­con­
sis­tent scientific evidence.
Level C—Recommendations are based primarily on con­
sen­sus and expert opinion.

20 Practice Bulletin No. 168