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Hadda Condino
The first 3 recommendations apply to individuals who have a cervix, regardless of their sexual history or HPV vaccination status. These recommendations do not apply to individuals who have been diagnosed with a high-grade precancerous cervical lesion or cervical cancer. These recommendations also do not apply to individuals with in utero exposure to diethylstilbestrol or those who have a compromised immune system (eg, women living with HIV).
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment.
The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms.
The number of deaths from cervical cancer in the United States have decreased substantially since the implementation of widespread cervical cancer screening and continue to decline, from 2.8 per 100,000 women in 2000 to 2.3 deaths per 100,000 women in 2015.1 Most cases of cervical cancer occur among women who have not been adequately screened.2 Strategies that aim to ensure that all women are appropriately screened and receive adequate follow-up are most likely to succeed in further reducing cervical cancer incidence and mortality in the United States.
The USPSTF found convincing evidence that screening with cervical cytology alone, primary testing for high-risk HPV types (hrHPV testing) alone, or in combination at the same time (cotesting) can detect high-grade precancerous cervical lesions and cervical cancer.
The USPSTF concludes with high certainty that the benefits of screening every 3 years with cytology alone in women aged 21 to 29 years substantially outweigh the harms. The USPSTF concludes with high certainty that the benefits of screening every 3 years with cytology alone, every 5 years with hrHPV testing alone, or in combination in women aged 30 to 65 years outweigh the harms.
The USPSTF concludes with moderate certainty that the benefits of screening in women older than 65 years who have had adequate prior screening and are not otherwise at high risk for cervical cancer do not outweigh the potential harms.
The USPSTF concludes with high certainty that the harms of screening in women who have had a hysterectomy with removal of the cervix for indications other than a high-grade precancerous lesion or cervical cancer outweigh the benefits.
This recommendation statement applies to all asymptomatic individuals with a cervix, regardless of their sexual history. This recommendation statement does not apply to women who have been diagnosed with a high-grade precancerous cervical lesion or cervical cancer, women with in utero exposure to diethylstilbestrol, or women who have a compromised immune system (eg, women living with HIV).
High-risk HPV infection is associated with nearly all cases of cervical cancer, and women are exposed to hrHPV through sexual intercourse. Although a large proportion of HPV infections resolve spontaneously, the high likelihood of exposure to hrHPV means that women are at risk for precancerous lesions and cervical cancer.
Certain risk factors increase risk for cervical cancer, including HIV infection, a compromised immune system, in utero exposure to diethylstilbestrol, and previous treatment of a high-grade precancerous lesion or cervical cancer. Women with these risk factors are not included in this recommendation and should receive individualized follow-up. Women who have had a hysterectomy with removal of the cervix and do not have a history of a high-grade precancerous lesion or cervical cancer are not at risk for cervical cancer and should not be screened. As part of the clinical evaluation, clinicians should confirm through review of surgical records or direct examination that the cervix was removed.
Current evidence indicates that there are no clinically important differences between liquid-based cytology and conventional cytology. A variety of platforms are used to detect hrHPV; most use either signal or nucleic acid amplification methods. Published trials of hrHPV testing used in situ hybridization, polymerase chain reaction, and hybrid capture technology to test for HPV strains associated with cervical cancer. hrHPV testing has been used for primary screening, cotesting with cytology, and follow-up testing of positive cytology results (reflex hrHPV).2
Screening with cytology alone, hrHPV testing alone, and both in combination offer a reasonable balance between benefits and harms for women aged 30 to 65 years; women in this age group should discuss with their health care professional which testing strategy is best for them. Evidence from randomized clinical trials (RCTs) and decision modeling studies suggest that screening with cytology alone is slightly less sensitive for detecting CIN 2 and CIN 3 than screening with hrHPV testing alone. Although screening with hrHPV testing alone or in combination with cytology detects more cases of CIN 2 and CIN 3, this method results in more diagnostic colposcopies for each case detected.2-5
There are a number of different protocols for triage of abnormal results from screening with cytology, hrHPV testing, or cotesting. Clinical trial evidence and modeling suggest that different triage protocols have generally similar detection rates for CIN 2 and CIN 3; however, proceeding directly to diagnostic colposcopy without additional triage leads to a much greater number of colposcopies compared with using other triage protocols. Maintaining comparable benefits and harms of screening with cytology alone or hrHPV testing alone requires that patients, clinicians, and health care organizations adhere to currently recommended protocols for repeat testing, diagnostic colposcopy, and treatment.6,7
Cervical cancer is rare before age 21 years.8 Exposure of cervical cells to hrHPV during vaginal intercourse may lead to cervical carcinogenesis, but the process has multiple steps, involves regression, and is generally not rapid. Because of the slow progression of disease and the high likelihood of regression in this age group, evidence suggests that screening earlier than age 21 years, regardless of sexual history, would lead to more harm than benefit. Treatment of CIN 2 or CIN 3 among women younger than 21 years may increase risk for adverse pregnancy outcomes.2,8
Joint guidelines from the American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology (ACS/ASCCP/ASCP) define adequate prior screening as 3 consecutive negative cytology results or 2 consecutive negative cotesting results within 10 years before stopping screening, with the most recent test occurring within 5 years.6 The guidelines further state that routine screening should continue for at least 20 years after spontaneous regression or appropriate management of a precancerous lesion, even if this extends screening past age 65 years. Once screening has stopped, it should not resume in women older than 65 years, even if they report having a new sexual partner.
Screening may be clinically indicated in older women with an inadequate or unknown screening history. Recent data suggest that one-fourth of women aged 45 to 64 years have not been screened for cervical cancer in the preceding 3 years.9 In particular, women with limited access to care, women from racial/ethnic minority groups, and women from countries where screening is not available may be less likely to meet criteria for adequate prior screening. Certain considerations may also support screening in women older than 65 years who are otherwise at high risk (ie, women with a history of high-grade precancerous lesions or cervical cancer, in utero exposure to diethylstilbestrol, or a compromised immune system).2
Screening more frequently than every 3 years with cytology alone confers little additional benefit, with a large increase in harms, including additional procedures and assessment and treatment of transient lesions. Treatment of lesions that would otherwise resolve on their own is harmful because it can lead to procedures with unwanted adverse effects, including the potential for cervical incompetence and preterm labor during pregnancy. Evidence from RCTs, observational studies, and modeling studies suggest that a 5-year screening interval for primary hrHPV testing alone or cotesting offers the best balance of benefits and harms. Screening more frequently than every 5 years with primary hrHPV testing alone or cotesting does not substantially improve benefit but significantly increases the number of screening tests and colposcopies.
Screening aims to identify high-grade precancerous cervical lesions to prevent progression to cervical cancer. High-grade cervical lesions may be treated with excisional and ablative therapies. Early-stage cervical cancer may be treated with surgery (hysterectomy) or chemotherapy. Treatment of precancerous lesions is less invasive than treatment of cancer.2
The incidence of and mortality from cervical cancer remain relatively high among certain populations. The overall mortality rate from cervical cancer among African American women is 10.1 deaths per 100,000 women,10 which is more than twice the rate among white women (when adjusted for hysterectomy rate), although the gap has narrowed over time. Mortality is higher among older African American women. Several studies have found that African American women are screened for cervical cancer at rates similar to those for white women and that inadequate follow-up after screening and differences in treatment may be important contributing factors. The higher mortality rate in African American women may also be attributable, in part, to the higher than average rate of adenocarcinoma, which carries a worse prognosis than the most common type of cervical cancer (squamous cell carcinoma).10-12
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