Find out more about the new cervical cancer screening (CCS) guidelines that were issued by the American Society for Colposcopy and Cervical Pathology (ASCCP) and American Cancer Society (ACS). We walk you through the updates and explain the overall importance of ensuring that women do not fall off their testing schedule, whether clinicians are using cytology, co-testing, or primary HPV testing. We also review triage methods, FDA-approved tests, and the role of extended genotyping. Discover how to improve risk stratification and risk-based patient management and what impact regular CCS can have on health outcomes.
Cervical Cancer Testing and How to Conduct Risk-Based Management
Cervical Cancer Testing and How to Conduct Risk-Based Management
Cervical cancer was once the leading cause of cancer death in women in the United States, but the introduction of cervical cancer screening (CCS) has helped drastically reduce cervical cancer-related mortality.1 Screening tests play a vital role in the prevention of cervical cancer because when detected early, cervical cancer is highly treatable and associated with long survival and a good quality of life.2
Improved understanding of cervical cancer, knowledge of different HPV types and their associated risks, increased patient outcomes data, and changes in screening test technology have led to new recommendations for cervical cancer screening.3 In recent years, updates have been released by the American Cancer Society (ACS) and the American Society for Colposcopy and Cervical Pathology (ASCCP). These guidelines provide evidence-based guidance for cervical cancer screening which aims to improve patient outcomes in relation to cervical cancer.
Cervical Cancer Screening Guideline Updates
The 2012 ACS guidelines recommended cytology testing beginning at 21 years of age with testing every 3 years until age 30. From ages 30 to 65 years, co-testing was recommended at 3-year intervals. The use of primary HPV testing alone was not recommended as a screening method in most clinical settings.3
The updated 2020 ACS guidelines recommend the use of primary HPV testing every 5 years beginning at age 25. This recommendation is based on the sensitivity of the primary HPV test and its superiority to cytology in identifying CIN3 and cervical cancers. It also has a high negative predictive value which allows for extended time between recommended screenings. Of note, guidelines specifically recommend the use of FDA-approved tests for primary HPV testing. Two such tests are currently available: the Roche cobas® and BD Onclarity™.
Due to the potential lack of accessibility to FDA-approved primary HPV testing, the ACS recognizes the need for a transition period from current to recommended practices. Options for cytology testing alone or as part of co-testing will continue to play a role in CCS as practices evolve and access to primary HPV testing improves.3
New guidelines recommend initial screening at 25 years of age instead of the previously recommended 21 years. The prevalence of HPV is high in many women under 25, but there is very little cervical cancer and low rates of CIN3+. Additionally, the HPV vaccine has played a key role in reducing HPV 16, 18, and other high-risk HPV types. At this time, over 50% of the target population has received at least one dose of the HPV vaccine. As HPV-vaccinated cohorts have reached the age of screening, detection of HPV types 16, 18, and other high-risk types has declined. This has made screening prior to age 25 unnecessary for women at average risk of cervical cancer.
Guidance for the discontinuation of cervical cancer screening has also changed. Screening can now be concluded at 65 years of age if two major requirements are met. Women must have no history of a prior CIN grade 2 or higher within the past 25 years, and they must have a documented negative screening in the past 10 years.
In 2019, the ASCCP released new risk-based guidance for the management of abnormal CCS results. Primary HPV testing has a low positive predictive value, meaning that many women can test HPV positive without having underlying disease. Due to this, the ASCCP’s new guidelines recommend that all positive primary HPV tests, regardless of genotype, have additional triage testing performed.4 A triage test is done for women who have a positive screening result and helps determine if they should be referred for colposcopy, receive continued surveillance, or be released to primary screening. Recommendations for colposcopy, treatment, or surveillance are based on a patient’s risk factors, which are determined by current screening results and previous screening history.5 The key difference of the 2019/2020 recommendations from previous guidelines is that “recommendations are based on risk, not results.” That is, the decision to undertake colposcopy, treatment, or surveillance is predicated on a patient's risk of CIN 3+6,7—as determined by a combination of current results and past history (including unknown history). Thus, the same current test results may yield different management recommendations depending on the history of recent past test results. A new principle cited in the ASCCP 2019/2020 guidelines is: “HPV-based testing is the basis for risk estimation.”The document notes: “The term HPV-based testing is used throughout this document and refers to use of either primary HPV testing alone or HPV testing in conjunction with cervical cytology (co-testing).”4
FDA-Approved Cervical Cancer Screening Tests
There are 3 main types of testing available for evaluating cervical cancer or cervical cancer dysplasia risk: cytology, primary HPV testing, and co-testing (Table 1).
Cytology is a pathology assessment performed by a cytopathologist which examines cells in a sample taken from the cervix. There is currently no FDA-approved cytology-alone assay. FDA-approved cytology testing is limited to co-testing algorithms, which incorporate both HPV DNA evaluation and cytology. While some tests only identify the presence or absence of high-risk HPV, other tests specifically identify HPV types 16 and 18 because they cause the greatest concern for progression to severe dysplasia and malignancy. Some tests also look for non-type 16 or 18 high-risk HPV types, such as the Aptima® HPV 16 18/45 and the BD Onclarity™ HPV.
Primary HPV testing is a cost-effective method that can provide powerful information about a woman’s risk of cervical cancer. Prior history of primary HPV testing also provides helpful background knowledge to guide clinical decision-making regarding cervical cancer screening and treatment.
Two primary HPV tests are available that evaluate the DNA of oncogenic HPV via a sample from the cervix: cobas® HPV and Onclarity™ HPV. The cobas® HPV tests for HPV types 16 and 18 and groups other high-risk types into a detection group. Onclarity™ HPV provides a more detailed overview of the presence of HPV types 16 and 18, as well as other high-risk types. Identification of high-risk HPV types can provide valuable information about the potential for more severe cervical disease, such as dysplasia or malignancy. It also aids in the identification of cases where disease is not likely to proceed to a serious clinical outcome and, therefore, may not need increased surveillance.
Clinical Implication of Extended Genotyping
HPV types 16 and 18 are classified as high risk and require immediate attention when identified. However, not all non-type 16/18 high-risk genotypes carry the same risk of cervical cancer. Research conducted by the National Cancer Institute in collaboration with Kaiser Permanente has shown that not all non-16/18 high-risk types behave the same. For example, types 33, 31, 35, and 52 have a lower risk than types 16 and 18 but a higher risk than types 58, 66, and 51. Because not all non-16/18 high-risk genotypes carry the same risk of cervical cancer, it may be possible to tease out distinct recommendations based on differences between low-, moderate-, and high-risk genotypes. More comprehensive genomic assessments could also contribute to future CCS management algorithms and help reduce costs associated with cervical cancer screening. Utilizing cervical cancer screening tests that allow for the delineation of individual HPV genotypes and clusters will optimize patient management strategies. Since 2015, a number of large clinical trials have evaluated and confirmed the clinical utility of extended genotyping for cervical cancer screening and triage.8,9,10 Additionally, the need for expanded HPV genotyping for cervical screening has been recognized since 2016.11 The utilization of HPV genotypes with the screening test result offers the ability to improve risk stratification and optimize risk-based patient management.
Cervical cancer screening is a powerful tool that has helped reduce the mortality rate of cervical cancer. In recent years, both the American Cancer Society and the American Society for Colposcopy and Cervical Pathology have released updated guidance regarding cervical cancer screening. These guidelines provide evidence-based recommendations for cervical cancer screenings, which can help improve patient outcomes. It is imperative that clinicians ensure their patients receive regular cervical cancer screenings at recommended intervals and recognize the value of primary HPV screening as a cervical cancer screening tool, not an STD test. Clinicians should also educate their patients about the importance of regular cervical cancer screenings, what the screenings test for, and the impact they can have on health outcomes.
- Cervical cancer statistics. Centers for Disease Control and Prevention. June 8, 2021. https://www.cdc.gov/cancer/cervical/statistics/index.htm
- Basic information about cervical cancer. Centers for Disease Control and Prevention. January 12, 2021. https://www.cdc.gov/cancer/cervical/basic_info/index.htm
- Fontham ETH, Wolf AMD, Church TR, et al. Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society. CA Cancer J Clin. 2020;70(5):321-346. doi:10.3322/caac.21628
- 2019 ASCCP risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors: erratum. J Low Genit Tract Dis. 2020;24(4):427. doi:10.1097/lgt.0000000000000563
- Wentzensen N. Triage of HPV-positive women in cervical cancer screening. Lancet Oncol. 2013;14(2):107-109.
- Elfgren K, Elfström KM, Naucler P, Arnheim-Dahlström L, Dillner J. Management of women with human papillomavirus persistence: long‐term follow‐up of a randomized clinical trial. Am J Obstet Gynecol. 2017;216(3):264.e1-264.e7.
- Aro K, Nieminen P, Louvanto K, et al. Age‐specific HPV type distribution in high‐grade cervical disease in screened and unvaccinated women. Gynecol Oncol. 2019;154(2):354-359.
- Wright TC Jr, Stoler MH, Parvu V, et al. Detection of cervical neoplasia by human papillomavirus testing in an atypical squamous cells‐undetermined significance population: results of the Becton Dickinson Onclarity trial. Am J Clin Pathol. 2019;151(1):53-62.
- Schiffman M, Hyun N, Raine-Bennett TR, et al. A cohort study of cervical screening using partial HPV typing and cytology triage. Int J Cancer. 2016;139(11):2606-2615.
- Stoler MH, Wright TC, Parvu V, et al. HPV testing with 16, 18, and 45 genotyping stratifies cancer risk for women with normal cytology. Am J Clin Pathol. 2019;151(4):433-442.
- Cuzick J, Wheeler C. Need for expanded HPV genotyping for cervical screening. Papillomavirus Res. 2016;2:112-115.
What changed in the recent CCS guideline updates from the ASCCP and ACS? Stay up to date so you can better triage and treat your patients.
Available credits: 0.25
In accordance with the ACCME Standards for Commercial Support, Global Learning Collaborative (GLC) requires that individuals in a position to control the content of an educational activity disclose all relevant financial relationships with any commercial interest. GLC resolves all conflicts of interest to ensure independence, objectivity, balance, and scientific rigor in all its educational programs.
Anna-Barbara Moscicki, MD
Professor of Pediatrics
Chief, Adolescent and Young Adult Medicine
Los Angeles, CA
Consulting Fees: Merck
Lee Philip Shulman, MD, FACMG, FACOG
The Anna Ross Lapham Professor in Obstetrics and Gynecology (Clinical Genetics)
Feinberg School of Medicine
Consulting Fees: Biogix, Celula, CooperSurgical, Natera, Vermillion/Aspira
Commercial Interest Speakers Bureau: Bayer, Lupin Pharmaceuticals, Inc., Myriad
- Sean T. Barrett has nothing to disclose.
- Sue Grossman has nothing to disclose.
- Libby Lurwick has nothing to disclose.
- Estelle Perera has nothing to disclose.
- Robert Schneider, MSW, has nothing to disclose.
After participating in this educational activity, participants should be better able to:
- Describe the key recommendations from the 2019 ASCCP CCS Guidelines and 2020 ACS Guideline update regarding risk stratification
- Formulate strategies that maximize the risk stratification obtained using extended genotyping within clinical practice
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Nanette F. Santoro, MDPeer