Whom to Screen

Screening after Hysterectomy

Screening Modality and Frequency

Screening Tests

• Liquid-based cytology

• Conventional smear cytology

• HPV testing

• Computerized rescreening

• Algorithm-based screening

Patient Education/Counseling

• To provide recommendations (evidence-based and consensus-based) on cervical cancer screening
• To assist primary care and specialist physicians and other health care professionals in counseling asymptomatic adolescents and adults about cervical cancer screening procedures

• To identify the optimal cervical screening tool (conventional cytology, liquid based cytology, or HPV DNA testing)
• To evaluate whether organized cervical screening programs with recall mechanisms reduce the incidence of and mortality due to cervical cancer compared to spontaneous cervical screening
• To identify the most appropriate time for initiation and cessation of cervical screening
• To identify the time interval at which women should be screened
• To identify whether women in special circumstances should be screened (i.e., pregnant women, women post-hysterectomy, HIV positive women, women who have sex with women)
• To identify the optimal management for women with abnormal cytology (up to but not including colposcopy/HPV management)

• To implement an evidenced-based strategy for cancer screening in adults

• To summarize the current USPSTF recommendations on screening for cervical cancer and the supporting evidence
• To update the 1996 recommendations contained in the Guide to Clinical Preventive Services, Second Edition

• United States
• Asymptomatic adult women 21 years of age and older and females under age 21 who are sexually active who have had none of the following:
  • Hysterectomy with total removal of the cervix for a benign condition
  • Hysterectomy with total removal of the cervix for a precancerous or cancerous condition of the uterus, cervix, or vagina
  • HIV infection and/or immunosuppression (due to organ transplantation or other condition)
  • A single positive HPV test
  • Persistently positive HPV tests
  • A recent abnormal cytologic result
  • Previous diagnosis of cervical cancer or CIN grade 2/3
• Asymptomatic adolescent and adult females with a cytology smear of ASC-US
• Asymptomatic adult women who have had a hysterectomy with total removal of the cervix for a benign condition of the uterus, cervix, or vagina
• Women who are infected with HIV, are immunosuppressed (e.g., due to organ transplantation or other condition), or who have been previously diagnosed with cervical cancer or CIN grade 2/3

• Women in Ontario, Canada
• All women who are, or have ever been, sexually active

Cervical Cancer Screening Recommendations

• Women in the United States
• Women starting within 3 years after onset of vaginal intercourse
• Women age 21 and older
• Women who have undergone a total hysterectomy

• Women in the United States
• Women who have been sexually active and have a cervix
• Women older than age 65
• Women who have had a total hysterectomy for benign disease

Advanced Practice Nurses

Allied Health Personnel

Nurses

Physician Assistants

Physicians

Physicians

Physicians

Physicians

Recommendations: Effectiveness of Cervical Cancer Primary Screening Tests in Asymptomatic, Average-Risk Women

Routine cervical cancer screening is recommended for all asymptomatic, average-risk women. (Evidence-based: B)

Recommendations: Optimal Age to Begin and End Screening in Asymptomatic, Average-risk Women

Initiation of cervical cancer screening is recommended approximately 3 years after first sexual intercourse or by the age of 21, whichever comes first.*‡ (Consensus-based)

Routine screening for cervical cancer for women older than age 65 is not recommended if they have had adequate recent screening** with normal results on their last cytology (and HPV test if applicable). (Evidence-based: D)

• *The Guideline Development Team (GDT) recognizes that the age to begin screening may not adequately reflect the current The Health Plan Employer Data and Information Set (HEDIS) measures. Some regions may choose to offer screening at a younger age. The HEDIS®* cervical cancer screening rate estimates the percentage of women aged 21 to 64 that were enrolled in the health plan and who had one cytology test during measurement year or the two years prior.
• ‡Routine cervical cancer screening continues to be recommended for women who have received the HPV vaccine. For additional information, see Kaiser Permanente (KP) National HPV Vaccine Practice Resource online at https://cl.kp.org/pkc/control/login.
• **The Guideline Development Team defined adequate recent screening as older women who have had three or more documented, consecutive, technically satisfactory normal/negative cervical cytology tests, and who have had no abnormal/positive cytology tests within the last 10 years.

Screening Initiation

Cervical cytology screening should be initiated within three years of first vaginal sexual activity (i.e., vaginal intercourse, vaginal/oral, and/or vaginal/digital sexual activity) (C-III).

Screening Cessation

Screening may be discontinued after the age of 70 if there is an adequate negative screening history in the previous 10 years (i.e., 3 to 4 negative tests) (B-II).

• Initiate. Start within 3 years after onset of vaginal intercourse [B] or at age 21 for women who are not sexually active [D].
• Terminate. Screening may be discontinued in women past age 65 (as recommended by the USPSTF) or age 70 (as recommended by the ACS and the NCCN) who have at least three normal or negative smears in the past 10 years and no previous history of cervical abnormality [C].

• The USPSTF strongly recommends screening for cervical cancer in women who have been sexually active and have a cervix. A recommendation.

  The USPSTF found good evidence from multiple observational studies that screening with cervical cytology (Pap smears) reduces incidence of and mortality from cervical cancer. Direct evidence to determine the optimal starting and stopping age and interval for screening is limited. Indirect evidence suggests most of the benefit can be obtained by beginning screening within 3 years of onset of sexual activity or age 21 (whichever comes first) and screening at least every 3 years (see Clinical Considerations below). The USPSTF concludes that the benefits of screening substantially outweigh potential harms.

• The USPSTF recommends against routinely screening women older than age 65 for cervical cancer if they have had adequate recent screening with normal Pap smears and are not otherwise at high risk for cervical cancer (see Clinical Considerations below). D recommendation.

  The USPSTF found limited evidence to determine the benefits of continued screening in women older than 65. The yield of screening is low in previously screened women older than 65 due to the declining incidence of high-grade cervical lesions after middle age. There is fair evidence that screening women older than 65 is associated with an increased risk for potential harms, including false-positive results and invasive procedures. The USPSTF concludes that the potential harms of screening are likely to exceed benefits among older women who have had normal results previously and who are not otherwise at high risk for cervical cancer.

Clinical Considerations

• The optimal age to begin screening is unknown. Data on natural history of HPV infection and the incidence of high-grade lesions and cervical cancer suggest that screening can safely be delayed until 3 years after onset of sexual activity or until age 21, whichever comes first. Although there is little value in screening women who have never been sexually active, many U.S. organizations recommend routine screening by age 18 or 21 for all women, based on the generally high prevalence of sexual activity by that age in the U.S. and concerns that clinicians may not always obtain accurate sexual histories.
• Discontinuation of cervical cancer screening in older women is appropriate, provided women have had adequate recent screening with normal Pap results. The optimal age to discontinue screening is not clear, but risk of cervical cancer and yield of screening decline steadily through middle age. The USPSTF found evidence that yield of screening was low in previously screened women after age 65. New ACS recommendations suggest stopping cervical cancer screening at age 70. Screening is recommended in older women who have not been previously screened, when information about previous screening is unavailable, or when screening is unlikely to have occurred in the past (e.g., among women from countries without screening programs). Evidence is limited to define "adequate recent screening." The ACS guidelines recommend that older women who have had three or more documented, consecutive, technically satisfactory normal/negative cervical cytology tests, and who have had no abnormal/positive cytology tests within the last 10 years, can safely stop screening.
• A majority of cases of invasive cervical cancer occur in women who are not adequately screened. Clinicians, hospitals, and health plans should develop systems to identify and screen the subgroup of women who have had no screening or who have had inadequate past screening.

Recommendations: Optimal Cervical Cancer Screening Strategy for Women Who Have Had a Total Hysterectomy for a Benign Condition.

Routine cytology screening is not recommended for women who have had a total hysterectomy for a benign condition unless there was a history of CIN grade 2/3. (Evidence-based: D)

Three consecutive negative cytology results with or without HPV testing are recommended prior to discontinuation of screening in women who have a history of CIN grade 2/3 and a subsequent hysterectomy for a benign condition. (Consensus-based)

• Screening can be discontinued in women who have undergone total hysterectomy for benign causes with no history of cervical dysplasia or human papillomavirus (C-III).
• Women who have undergone subtotal hysterectomy (with an intact cervix) should continue screening according to the guidelines.

• Women who have undergone a total hysterectomy do not require screening unless the hysterectomy was performed because of cervical cancer or its precursors [C].

Clinical Background. Women who have undergone a total hysterectomy (with removal of the cervix) for benign gynecologic disease do not need to undergo screening with vaginal cytology. However, a health care provider should confirm and/or document via physical exam and review of the pathology report (when available) that the cervix was completely removed. Women who have had a subtotal hysterectomy should continue cervical cancer screening as per current guidelines.

• The USPSTF recommends against routine Pap smear screening in women who have had a total hysterectomy for benign disease. D recommendation.

  The USPSTF found fair evidence that the yield of cytologic screening is very low in women after hysterectomy and poor evidence that screening to detect vaginal cancer improves health outcomes. The USPSTF concludes that potential harms of continued screening after hysterectomy are likely to exceed benefits.

Clinical Considerations

• Discontinuation of cytological screening after total hysterectomy for benign disease (e.g., no evidence of cervical neoplasia or cancer) is appropriate given the low yield of screening and the potential harms from false-positive results in this population. Clinicians should confirm that a total hysterectomy was performed (through surgical records or inspecting for absence of a cervix); screening may be appropriate when the indications for hysterectomy are uncertain. ACS and ACOG recommend continuing cytologic screening after hysterectomy for women with a history of invasive cervical cancer or DES exposure due to increased risk for vaginal neoplasms, but data on the yield of such screening are sparse.

Recommendations: Effectiveness of Cervical Cancer Primary Screening Tests in Asymptomatic, Average-Risk Women

Either of the following tests are options for cervical cancer screening in asymptomatic, average-risk women under age 30.

• Conventional cytology (Evidence-based: B)
• Liquid-based cytology (Consensus-based)

All of the following tests are acceptable options for cervical cancer screening in asymptomatic, average-risk women age 30 and older.

• Conventional cytology (Evidence-based: B)
• Conventional cytology and HPV testing*‡** cytology (Consensus-based)
• Liquid-based cytology (Consensus-based)
• Liquid-based cytology and HPV testing*‡** cytology (Consensus-based)

  *HPV testing has not been FDA approved as a stand alone test for primary screening.

  ‡Combined cytology and HPV testing provides useful risk-stratification

  **Hybrid Capture 2 (HC2) Testing Device.

No recommendation for or against routine use of computer-assisted slide evaluation or automated rescreening of cytology slides. (Evidence-based: I)

Recommendations: Cervical Cancer Screening Intervals in Asymptomatic, Average-risk Women

The following screening intervals are recommended:

• Cytology alone: every 3 years* (Consensus-based)
• Cytology + HPV (age 30 and older): every 3 years*‡ (Consensus-based)

  *Screen if more than 30 months has elapsed.

  ‡Hybrid Capture 2 (HC2) Testing Device.

No recommendation for or against routinely providing annual screening tests prior to beginning a triennial screening program. (Evidence-based: I)

Recommendations: Triage for ASC-US Results Using HPV Testing in Asymptomatic, Average-risk Women

HPV testing is recommended in women of all ages for triage of cytology results indicating ASC-US. (Evidence-based: B)

No recommendation for or against the use of HPV testing to triage women with cytologic results higher than ASC-US. (Evidence-based: I)

Recommendations: Screening in Women at Increased Risk of Cervical Cancer

Cytology and HPV testing are recommended at 6 months following treatment for CIN grade 2/3, and again at 24 months, with colposcopy for any positive result. Routine screening every 3 years can then be resumed indefinitely. (Consensus-based)

If HPV testing is not done, two cytology tests at 6 and 12 months after treatment are recommended, with colposcopy for a positive result, then annual cytologic screening indefinitely. (Consensus-based)

At least annual cytology with or without HPV testing is recommended for women who are immunosuppressed or HIV-positive. (Consensus-based)

Recommendation: Optimal Initial Management of Concurrent HPV-Positive and Cytology-Negative Cervical Screening Results

HPV and cytology retesting is recommended in 12 months, rather than immediate colposcopy, for management of women with initial concurrent HPV-positive and cytology-negative screening results. (Consensus-based).

Optimal Cervical Screening Tool

• Liquid-based cytology is the preferred tool for cervical cytology screening (B-II). Conventional smear cytology remains an acceptable alternative (C-III).

Screening Interval

• Screening should be done annually until there are three consecutive negative Pap tests (C-III).
• Screening should continue every two to three years after three annual negative Pap tests (B-II).
  • Screening at a three-year interval is recommended, supported by an adequate recall mechanism (B-II).
  • Women who have not been screened in more than five years should be screened annually until there are three consecutive negative Pap tests (C-III).

Note: These recommendations do not apply to women who have had previous abnormal Pap tests. See management of abnormal cytology section in original guideline document for further information.

Screening Women with Special Circumstances

• Immunocompromised or HIV positive women should receive annual screening (C-III).
  • Examples of situations where women may be immunocompromised include women who have received transplants and women who have undergone chemotherapy.
• Indications for screening frequency for pregnant women should be the same as women who are not pregnant (B-III). Manufacturer's recommendations for the use of individual screening tools in pregnancy should be taken into consideration.
• Women who have sex with women should follow the same cervical screening regimen as women who have sex with men (B-II).

Recommended Management for Women with Abnormal Cytology

ASCUS (Atypical squamous cells of uncertain significance)

• HPV DNA testing with cytology is recommended for women aged 30 or older with ASC-US (C-III).
  • If the HPV DNA test is positive, women should be referred for colposcopy. If the HPV DNA test is negative, women should have repeat cytology in 12 months. Once a woman has had two negative cytology test results, she should return to routine screening.
  • In the absence of HPV DNA testing, a repeat Pap test in six months is acceptable. If the Pap test is abnormal, women should be referred for colposcopy. If the Pap test is negative, women should have repeat cytology in another six months. Once a woman has had two negative Pap test results, she should return to routine screening.

Modality

Pap smear of cervical cells or liquid based cervical cytology (ThinPrep®).

Frequency

• Low risk. Annually with conventional Pap smears or every two years using the ThinPrep until age 30. Starting at age 30, women who have had three consecutive technically satisfactory normal or negative cytology results may be screened every two to three years [C]. ("Low risk" includes women who do not have a history of in utero exposure to DES, are not immunocompromised or HIV+, and have had three consecutive normal or negative cytology results.)
• High risk. Screen annually [D].

Rationale for Recommendations

Screening tests. The ThinPrep® system collects more cells and leads to better quality slides. The ThinPrep system is more sensitive (76% vs. 68%) and specific (86% vs. 79%) than Pap smear.

How often should screening be done. Screening intervals will vary depending on the cytologic method used. After women have undergone an initial conventional cervical cancer screening with a Pap smear, the procedure should be performed annually until age 30. If the initial screening test was based on the ThinPrep system, the procedure should be performed at least every two years until age 30. At age 30 or older, a physician and patient may elect to reduce the frequency of screening to every 2 to 3 years if the woman is low-risk (e.g., does not have a history of in utero exposure to DES, is not immunocompromised or HIV+) and has had three consecutive normal or negative cytology results.

New screening technology. The United States FDA has approved a computerized device (AutoPap 300) as an adjunct to manual screening. The system is used to rescreen negative smears and approximately 10% to 20% of slides are classified as abnormal using a computerized cellular analysis. These slides are then reviewed by a pathologist.

HPV testing. While routine testing on all patients for human HPV has been proposed as an alternative screening test, the high prevalence of HPV in young women and low positive predictive value for higher-grade lesions limits its usefulness. At the University of Michigan, HPV testing for high risk subtypes is currently performed on the ThinPrep samples from patients with an ASC-US pap smear. Patients > age 20 years old and positive for high risk HPV subtypes should be referred for colposcopy. HPV testing is not recommended in women < 20 years old. For patients < 20 years old and ASC-US or low grade abnormalities, repeat pap in 1 year. Adolescent patients are extremely unlikely to develop cervical neoplasia and have a relatively high rate of clearing the virus. If repeat pap in 1 year is still abnormal, then patient should be referred for colposcopy. If negative for high risk HPV subtypes, the women may be followed with a repeat pap smear in one year, based on the negative predictive value, of our current HPV test, being 98%.

• The U.S. Preventive Services Task Force (USPSTF) strongly recommends screening for cervical cancer in women who have been sexually active and have a cervix. A recommendation.

  The USPSTF found good evidence from multiple observational studies that screening with cervical cytology (Pap smears) reduces incidence of and mortality from cervical cancer. Direct evidence to determine the optimal starting and stopping age and interval for screening is limited. Indirect evidence suggests most of the benefit can be obtained by beginning screening within 3 years of onset of sexual activity or age 21 (whichever comes first) and screening at least every 3 years (see Clinical Considerations below). The USPSTF concludes that the benefits of screening substantially outweigh potential harms.

Clinical Considerations

• The USPSTF found no direct evidence that annual screening achieves better outcomes than screening every 3 years. Modeling studies suggest little added benefit of more frequent screening for most women. The majority of cervical cancers in the U.S. occur in women who have never been screened or who have not been screened within the past 5 years; additional cases occur in women who do not receive appropriate follow-up after an abnormal Pap smear. Because sensitivity of a single Pap test for high-grade lesions may only be 60% to 80%, however, most organizations in the U.S. recommend that annual Pap smears be performed until a specified number (usually 2 or 3) are cytologically normal before lengthening the screening interval. The ACS guidelines suggest waiting until age 30 before lengthening the screening interval; ACOG identifies additional risk factors that might justify annual screening, including a history of cervical neoplasia, infection with HPV or other STDs, or high-risk sexual behavior, but data are limited to determine the benefits of these strategies.
• The USPSTF concludes that the evidence is insufficient to recommend for or against the routine use of new technologies to screen for cervical cancer. I recommendation.

  The USPSTF found poor evidence to determine whether new technologies, such as liquid-based cytology, computerized rescreening, and algorithm based screening, are more effective than conventional Pap smear screening in reducing incidence of or mortality from invasive cervical cancer. Evidence to determine both sensitivity and specificity of new screening technologies is limited. As a result, the USPSTF concludes that it cannot determine whether the potential benefits of new screening devices relative to conventional Pap tests are sufficient to justify a possible increase in potential harms or costs.

• The USPSTF concludes that the evidence is insufficient to recommend for or against the routine use of HPV testing as a primary screening test for cervical cancer. I recommendation.

  The USPSTF found poor evidence to determine the benefits and potential harms of HPV screening as an adjunct or alternative to regular Pap smear screening. Trials are underway that should soon clarify the role of HPV testing in cervical cancer screening.

HPV Testing in Women with ASC-US

Liquid-based cytology permits testing of specimens for HPV, which may be useful in guiding management of women whose Pap smear reveals atypical squamous cells.

No recommendations offered

No recommendations offered

It is important that women who may not need a cervical cytology test obtain appropriate preventive health care, including contraception and prevention counseling, and screening and treatment of sexually transmitted diseases.

No recommendations offered

• Appropriate cervical cancer screening
• Reduced morbidity and mortality from cervical cancer

• Optimal use of cervical screening tools
• Reduced incidence and mortality due to cervical cancer
• Appropriate initiation, intervals, and cessation of cervical screening
• Optimal management of women with abnormal cytology

Reductions in Cancer Incidence and Mortality

Correlational studies show significant declines in both the incidence of cervical cancer and cervical cancer mortality rates in North American and western Europe following the introduction of screening programs. The reduction in mortality correlated closely with the intensity of the screening. Case control studies support the correlational data and show a decrease in the incidence of invasive cancer by 60 to 90%. Increased frequency of screening is associated with a greater reduction in rate of cervical cancer.

Reductions in Cancer Incidence and Mortality

Detection of cervical cancer in its earliest stages is lifesaving, as survival of cancer of the cervix uteri depends heavily on stage at diagnosis. Although 92 percent of women will survive 5 years when the cancer is localized, only 13 percent will survive distant disease. Introduction of screening programs to populations naive to screening reduces cervical cancer rates by 60 to 90 percent within 3 years of implementation. This reduction of mortality and morbidity with introduction of the Pap test is consistent and dramatic across populations. Although no prospective trial of Pap screening has ever been conducted, correlational studies of cervical cancer trends in countries in North America and Europe demonstrate dramatic reductions in incidence of invasive cervical cancer and a 20 to 60 percent reduction in cervical cancer mortality.

• Inconvenience, anxiety, and adverse effects of tests (e.g., discomfort, pain)
• Unnecessary tests due to false-positive test results
• False reassurance from false-negative test results, neglect to follow-up, progression of cancer

None stated

None stated

• The USPSTF concludes that the potential harms of screening are likely to exceed benefits among older women who have had normal results previously and who are not otherwise at high risk for cervical cancer.
• The USPSTF concludes that potential harms of continued screening after hysterectomy are likely to exceed benefits.
• The USPSTF concludes that it cannot determine whether the potential benefits of new screening devices relative to conventional Pap tests are sufficient to justify a possible increase in potential harms or costs. The USPSTF did not identify studies that specifically addressed harms of new technologies for cervical cancer screening. Better data on the performance characteristics (sensitivity, specificity, and predictive values) of the new screening technologies are needed to determine the risk for harm to an individual patient. Although the data are limited, on average these tools improve sensitivity and reduce specificity. This finding suggests that increased detection of low-grade lesions and false positives are the primary potential sources of harm; i.e., harm may take the form of increased evaluations, including repeated Pap tests and biopsies; possible unnecessary treatment for low-grade lesions; and psychological distress for the women diagnosed with low grade lesions that may not have been clinically important. These harms are poorly documented for conventional Pap testing and have not yet been assessed for new technologies.
• With regard to HPV testing, the USPSTF did not identify any studies that quantified harms. Potential harms commented on in the literature include stigma, partner discord, adverse effects of labeling some women as being at high risk for cervical cancer, and the potential undermining of routine cytologic screening known to be effective.

Recommendations are classified as either "evidence-based (A-D, I)" or "consensus-based."

• Evidence-based: sufficient number of high-quality studies from which to draw a conclusion, and the recommended practice is consistent with the findings of the evidence. A recommendation can also be considered "evidence-based"" if there is insufficient evidence and no practice is recommended.
• Consensus-based: insufficient evidence and a practice is recommended based on the consensus or expert opinion of the Guideline Development Team (GDT).

Label and Language of Recommendations*

^[a] All statements specify the population for which the recommendation is intended.

*Recommendations should be labeled and given an evidence grade. The evidence grade should appear in the rationale. Evidence is graded with respect to the degree it supports the specific clinical recommendation. For example, there may be good evidence that Drugs 1 and 2 are effective for Condition A, but no evidence that Drug 1 is more effective than Drug 2. If the recommendation is to use either Drug 1 or 2, the evidence is good. If the recommendation is to use Drug 1 in preference to Drug 2, the evidence is insufficient.

Quality of Evidence

I: Evidence from at least 1 randomized controlled trial

II: Evidence from at least 1 clinical trial without randomization, from cohort or case-controlled analytic studies, or from multiple time series studies or dramatic results from uncontrolled experiments

III: Evidence from opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees

Strength of Recommendation

A: Good evidence for efficacy and substantial clinical benefit support recommendation for use.

B: Moderate evidence for efficacy or only limited clinical benefit support recommendation for use.

C: Evidence for efficacy is insufficient to support a recommendation for or against use, but recommendations may be made on other grounds.

D: Moderate evidence for lack of efficacy or for adverse outcome supports a recommendation against use.

E: Good evidence for lack of efficacy or for adverse outcome supports a recommendation against use.

Levels of evidence reflect the best available literature in support of an intervention or test:

A = Randomized controlled trials

B = Controlled trials, no randomization

C = Observational trials

D = Opinion of expert panel

Quality of Evidence

The USPSTF grades the quality of the overall evidence for a service on a 3-point scale (good, fair, poor):

Good: Evidence includes consistent results from well-designed, well-conducted studies in representative populations that directly assess effects on health outcomes.

Fair: Evidence is sufficient to determine effects on health outcomes, but the strength of the evidence is limited by the number, quality, or consistency of the individual studies, generalizability to routine practice, or indirect nature of the evidence on health outcomes.

Poor: Evidence is insufficient to assess the effects on health outcomes because of limited number or power of studies, important flaws in their design or conduct, gaps in the chain of evidence, or lack of information on important health outcomes.

Strength of Recommendations

The U.S. Preventive Services Task Force (USPSTF) grades its recommendations according to one of five classifications (A, B, C, D, I) reflecting the strength of evidence and magnitude of net benefit (benefits minus harms).

A. The USPSTF strongly recommends that clinicians provide [the service] to eligible patients. The USPSTF found good evidence that [the service] improves important health outcomes and concludes that benefits substantially outweigh harms.

B. The USPSTF recommends that clinicians provide [this service] to eligible patients. The USPSTF found at least fair evidence that [the service] improves important health outcomes and concludes that benefits outweigh harms.

C. The USPSTF makes no recommendation for or against routine provision of [the service]. The USPSTF found at least fair evidence that [the service] can improve health outcomes but concludes that the balance of benefits and harms is too close to justify a general recommendation.

D. The USPSTF recommends against routinely providing [the service] to asymptomatic patients. The USPSTF found at least fair evidence that [the service] is ineffective or that harms outweigh benefits.

I. The USPSTF concludes that the evidence is insufficient to recommend for or against routinely providing [the service]. Evidence that the [service] is effective is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined.