Abstract
Table: of ContentsA. EXECUTIVE SUMMARY Updated US consensus guidelines for management of cervical screening abnormalities are needed to accommodate the 3 available cervical screening strategies: primary human papillomavirus (HPV) screening, cotesting with HPV testing and cervical cytology, and cervical cytology alone. New data indicate that a patient's risk of developing cervical precancer or cancer can be estimated using current screening test results and previous screening test and biopsy results, while considering personal factors such as age and immunosuppression. Routine screening applies only to asymptomatic individuals who do not require surveillance for prior abnormal screening results. The 2012 consensus guidelines were the first to be based on the principle of equal management for equal risk, specifically, the risk of a patient developing cervical cancer, estimated by the surrogate end point of the 5-year risk of cervical intraepithelial neoplasia (CIN) grade 3 (CIN 3) or more severe diagnoses (CIN 3+), regardless of which test combinations yielded this risk level. Introduction of risk-based guidelines in 2012 was a conceptual breakthrough, but the recommendations retained a continued reliance on complicated algorithms and insufficiently incorporated screening history. With a more nuanced understanding of how previous results affect risk, and more variables to consider, the 2019 guidelines further align management recommendations with current understanding of HPV natural history and cervical carcinogenesis. More frequent surveillance, colposcopy, and treatment are recommended for patients at progressively higher risk, whereas those at lower risk can defer colposcopy, undergo follow-up at longer surveillance intervals, and, when at sufficiently low risk, return to routine screening. Clearly defined risk thresholds to guide management are designed to continue functioning appropriately when population-level prevalence of CIN 3+ decreases because of HPV vaccination and also as new screening and triage tests are introduced. The revised guidelines provide a framework for incorporating new data and technologies as ongoing incremental recommendation revisions, minimizing the time needed to implement changes that are beneficial to patient care. B. INTRODUCTION This is the fourth American Society of Colposcopy and Cervical Pathology (ASCCP)-sponsored consensus guidelines for management of cervical cancer screening abnormalities, after the original consensus conferences in 20011 and subsequent updates in 20062 and 2012.3 An interim guidance publication providing management recommendations for primary HPV screening was released in 2015.4This document updates and replaces all previous guidance. The key difference between 2019 guidelines and previous versions is the change from primarily test results–based algorithms (e.g., "Colposcopy is recommended for patients with HPV-positive atypical squamous cells of undetermined significance [ASC-US], low-grade squamous intraepithelial lesion [LSIL]," etc.) to primarily "risk-based" guidelines (e.g., "Colposcopy is recommended for any combination of history and current test results yielding a 4.0% or greater probability of finding CIN 3+," etc.). See Box 1 for essential changes. Tables of risk estimates for possible combinations of current screening test results and screening history (including unknown history) have been generated from a prospective longitudinal cohort of more than 1.5 million patients followed for more than a decade at Kaiser Permanente Northern California (KPNC). All KPNC estimates of risk underlying guideline decisions are detailed in the accompanying article by Egemen et al.5 The applicability of these risk estimates to other United States regions and populations has been confirmed in other data sets from screening programs and clinical trials.6 Many patients, especially those with minor abnormalities, can be managed by identifying their risk level using Tables 1A to 5B in Egemen et al5 and linking it to a recommended clinical action (return to routine screening, surveillance with repeat testing at 1- or 3-year intervals, colposcopy, or treatment). To facilitate use of these tables, the same information will be accessible via smartphone app (for purchase) and web (no cost) through http://www.asccp.org. Decision aids may facilitate use of the tables.7 Common abnormalities are managed using risk estimates outlined in Section E, and rare abnormalities are managed via the result-specific consensus recommendations outlined in Sections G-K.TABLE 1: Participating OrganizationsBox 1. Essential Changes From Prior Management Guidelines 1) Recommendations are based on risk, not results. Recommendations of colposcopy, treatment, or surveillance will be based on a patient's risk of CIN 3+ determined by a combination of current results and past history (including unknown history). The same current test results may yield different management recommendations depending on the history of recent past test results. 2) Colposcopy can be deferred for certain patients. Repeat HPV testing or cotesting at 1 year is recommended for patients with minor screening abnormalities indicating HPV infection with low risk of underlying CIN 3+ (e.g., HPV-positive, low-grade cytologic abnormalities after a documented negative screening HPV test or cotest). 3) Guidance for expedited treatment is expanded (i.e., treatment without colposcopic biopsy). Expedited treatment was an option for patients with HSIL cytology in the 2012 guidelines; this guidance is now better defined. For non-pregnant patients 25 years or older, expedited treatment, defined as treatment without preceding colposcopic biopsy demonstrating CIN 2+, is preferred when the immediate risk of CIN 3+ is ≥60%, and is acceptable for those with risks between 25% and 60%. Expedited treatment is preferred for nonpregnant patients 25 years or older with high-grade squamous intraepithelial lesion (HSIL) cytology and concurrent positive testing for HPV genotype 16 (HPV 16) (i.e., HPV 16–positive HSIL cytology) and never or rarely screened patients with HPV-positive HSIL cytology regardless of HPV genotype. Shared decision-making should be used when considering expedited treatment, especially for patients with concerns about the potential impact of treatment on pregnancy outcomes. 4) Excisional treatment is preferred to ablative treatment for histologic HSIL (CIN 2 or CIN 3) in the United States. Excision is recommended for adenocarcinoma in situ (AIS). 5) Observation is preferred to treatment for CIN 1. 6) Histopathology reports based on Lower Anogenital Squamous Terminology (LAST)/World Health Organization (WHO) recommendations for reporting histologic HSIL should include CIN 2 or CIN 3 qualifiers, i.e., HSIL(CIN 2) and HSIL (CIN 3). 7) All positive primary HPV screening tests, regardless of genotype, should have additional reflex triage testing performed from the same laboratory specimen (e.g., reflex cytology). Additional testing from the same laboratory specimen is recommended because the findings may inform colposcopy practice. For example, those HPV-16 positive HSIL cytology qualify for expedited treatment. HPV 16 or 18 infections have the highest risk for CIN 3 and occult cancer, so additional evaluation (e.g., colposcopy with biopsy) is necessary even when cytology results are negative. If HPV 16 or 18 testing is positive, and additional laboratory testing of the same sample is not feasible, the patient should proceed directly to colposcopy. 8) Continued surveillance with HPV testing or cotesting at 3-year intervals for at least 25 years is recommended after treatment and initial post-treatment management of histologic HSIL, CIN 2, CIN 3, or AIS. Continued surveillance at 3-year intervals beyond 25 years is acceptable for as long as the patient's life expectancy and ability to be screened are not significantly compromised by serious health issues. The 2012 guidelines recommended return to 5-year screening intervals and did not specify when screening should cease. New evidence indicates that risk remains elevated for at least 25 years, with no evidence that treated patients ever return to risk levels compatible with 5-year intervals. 9) Surveillance with cytology alone is acceptable only if testing with HPV or cotesting is not feasible. Cytology is less sensitive than HPV testing for detection of precancer and is therefore recommended more often. Cytology is recommended at 6-month intervals when HPV testing or cotesting is recommended annually. Cytology is recommended annually when 3-year intervals are recommended for HPV or cotesting. 10) Human papilloma virus assays that are Food and Drug Administration (FDA)-approved for screening should be used for management according to their regulatory approval in the United States. (Note: all HPV testing in this document refers to testing for high-risk HPV types only). For all management indications, HPV mRNA and HPV DNA tests without FDA approval for primary screening alone should only be used as a cotest with cytology, unless sufficient, rigorous data are available to support use of these particular tests in management. The minimum amount of data required to generate a recommendation will include the patient's age and current test results, as we recognize that previous screening history is often not known. Increased precision of management guidance will be possible if information is available on test results within the past 5 years and previous precancer treatment within the past 25 years.3 Current results and past history are designed to generate the patient's risk estimate from data tables.5 Risk estimates are available for the following clinical situations: abnormal screening test results with unknown history, abnormal screening test results with medical record documentation of a preceding negative HPV test or cotest, surveillance of previous abnormal screening test results that d