Cancer is a major contributor to morbidity and mortality worldwide and is the second leading cause of death in the United States.1,2 The National Cancer Institute projects an estimated 1.9 million new cancer cases and more than 600,000 cancer-related deaths during 2021 (Table 1).2 Approximately 39% of Americans will be diagnosed with cancer at some point during their lifetime, with the median age at diagnosis of 66 years.2 Cancers with the highest incidence and overall mortality include cancers of the female breast, prostate, lung, and colon.2

Progress has been made to decrease cancer incidence and increase cancer survival. Much of this progress can be linked to decreases in tobacco use as well as implementation of cancer screening programs.3-5

Cancer TypeNew CasesDeaths
Breast Cancer (Female)281,55043,600
Prostate Cancer248,53034,130
Lung and Bronchus Cancer235,760131,880
Colorectal Cancer149,50052,980
Melanoma of the Skin106,1107,180
Bladder Cancer83,73017,200
Non-Hodgkin Lymphoma81,56020,720
Kidney and Renal Pelvis Cancer76,08013,780
Uterine Cancer66,57012,940
Cancer of Any Site1,898,160608,570
Credit: National Cancer Institute.2

Ideally, cancer screening programs detect disease at an asymptomatic stage, enabling early interventions and leading to measurable improvements in morbidity and mortality.5 Screening recommendations are based on cancer type, population to be screened, and accuracy of the test.5 The cancer type must have an effective treatment available that will lead to a significant improvement in quality of life and/or survival rates.4,5 A sufficiently high disease prevalence should be apparent in the population to be screened and the screening test should have high sensitivity and specificity.5

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While cancer screening tests can provide substantial population health benefits, clinicians must consider the potential for overdiagnosis, particularly of low-risk cancers with limited disease burden.5 Many common screening tests may expose patients to additional risks, such as potential carcinogenesis from radiation exposure.5,6 Lastly, providers should discuss the likelihood of false-positive test results with patients leading to possibly unnecessary diagnostic procedures and undue anxiety.5 Clinicians must actively engage in shared decision-making with bidirectional exchange of information around the screening test, disease, and patients’ values.5

Note: This review article focuses on cancer screening guidelines for average-risk individuals. Each professional organization uniquely evaluates the evidence base, and we are reporting guidelines with the highest level of evidence as defined by each recommending body. Alternate recommendations for individuals with above-average risk, such as those with a personal history of cancer, are not included in this article. Consult guidelines from specialist organizations when caring for individuals with above-average cancer risk.

Cervical Cancer

Historically, cervical cancer was one of the leading causes of cancer mortality among American women.7 An estimated 1 in 161 (0.6%) women in the US will develop cervical cancer during their lifetime and an estimated 14,480 new cases of cervical cancer are expected in 2021.3 The 5-year survival rate is 66%.2

The disease burden rate for cervical cancer decreased significantly with the widespread use of screening tests, allowing for the detection of treatable precancerous lesions.3,7 Current tests include the Papanicolaou test, also known as cytology (conventional cytology or liquid-based cytology); cotesting with cytology and human papillomavirus (HPV, including HPV DNA and HPV mRNA tests) screening; or HPV testing alone.8 Because HPV infections may be substantially oncogenic, cotesting screening methodologies are associated with improvement in testing sensitivity.8 Immunocompromised patients, including patients with HIV, may have an increased risk of cervical cancer; however, there are no consensus recommendations for screening this high-risk population. 7 Recommendations vary for those with in utero exposure to diethylstilbestrol.8

Cervical cancer screening guidelines from the US Preventive Service Task Force (USPSTF), American College of Obstetricians and Gynecologists (ACOG), and ACS vary slightly (Table 2).7-9 For average-risk women, screening begins at age 21 years (USPSTF and ACOG) or age 25 (ACS) regardless of whether or not the patient is sexually active.9 All of the guidelines recommend discontinuing screening at age 65 if the patient has adequate negative prior screening results. For management of abnormal screening findings, clinicians should utilize the American Society for Colposcopy and Cervical Pathology (ASCCP) algorithms.10

Table 2. Cervical Cancer Screening Guidelines

USPSTF (2018)9ACS (2020)7ACOG (2021)8
Age <21 y: no screeningAge <25 y: no screeningAge <21 y: no screening
Age 21-29 y: every 3 years with cervical cytology alone
Age 30-65 y:
• Cytology alone every 3 years
• hrHPV testing alone every 5 years
• Cotesting every 5 y
Age 25-65 y: starting at age 25 y, primary HPV test alone every 5 y (preferred)Age 21-29 y: every 3 y with cytology alone
Age 30-65 y:
• Cytology alone every 3 y;
• hrHPV testing alone every 5 y; or
• Co-testing every 5 y
Age >65 y: No screening after adequate negative prior screening resultsaAge >65 y: No screening after adequate negative prior screening resultsbAge >65 y: No screening after adequate negative prior screening resultsc
ACOG, American College of Obstetricians and Gynecologists; ACS, American Cancer Society; hrHPV, high-risk human papillomavirus; USPSTF, United States Preventative Services Task Force
aThree consecutive negative cytology results or 2 consecutive negative cotesting results within 10 years before stopping screening, with the most recent test occurring within 5 y.
bTwo consecutive, negative primary HPV tests, or 2 negative cotests or 3 negative cytology tests within the past 10 y, with the most recent test occurring within the past 3 to 5 y, depending on the test used.
cThree consecutive negative cytology results, 2 consecutive negative cotesting results.

This article originally appeared on Clinical Advisor