ORIGINAL RESEARCH ARTICLE: CERVIX AND HPV

An Introduction to the 2019 ASCCP Risk-Based Management

Consensus Guidelines
Mark Schiffman, MD,1 Nicolas Wentzensen, MD,1 Rebecca B. Perkins, MD,2 and Richard S. Guido, MD3

(J Low Genit Tract Dis 2020;24: 87–89) and simple consensus recommendations based on risk, to achieve
a “long shelf-life” for this version of the 2019 guidelines before

T he 2019 revision of the ASCCP Risk-Based Management

Consensus Guidelines expands upon the “risk-based” approach
another guidelines conference is needed, despite the abundance
of competing tests and strategies.
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introduced in 2012. It addresses the need for simplicity and stability

in clinical guidelines while anticipating continued technologic ad-
vances in cervical screening methods. This introduction explains THE GENERAL APPROACH TAKEN TO CREATE THE
why the 2019 revision was needed, describes the general approach NEW GUIDELINES
of the new guidelines, and outlines briefly how the new approach The ASCCP and NCI cooperatively planned and supported
will work in practice. the consensus process, with administrative support provided by
the ASCCP. The convening of the consensus group is described
in the main guidelines article. Once convened, the major task of
WHY THE 2019 REVISION WAS NEEDED the participating representatives was to decide on durable clinical
The revision was motivated by the complexity of the 2012 action thresholds, striving to represent US consensus as to what
guidelines and the queue of soon-to-be available new tests. It grad- clinical actions are recommended for increasing severity of cervi-
ually became clear that there were too many acceptable choices in cal screening abnormalities. The following axiomatic principles
use, or in final development, to continue as before. In a departure were followed: the main purpose of cervical screening in the
from previous versions, the 2019 guidelines therefore do not pres- United States is to find precancerous lesions (“precancer”) that
ent separate algorithm figures for most screening and triage combi- can be treated easily to prevent invasive cervical cancer. Putting
nations. For example, there are no algorithm figures entitled “Triage aside temporarily whether precancer is best defined as cervical
of ASC-US” or “Follow-up of HPV-Positive Results.” Dozens of al- intraepithelial neoplasia (CIN) 2/CIN 3/AIS, or CIN 3/
gorithm diagrams would have been required to cover the many adenocarcinoma in situ (AIS), or histologic high-grade squamous
test combinations now in use or proposed to be introduced soon intraepithelial lesion/AIS, there are a limited number of clinical
(such as extended genotyping or dual-stain cytology), along with actions available to clinicians and patients when faced with a cer-
the influence of past screening history on the meaning of current vical screening abnormality. Logically, a patient known to be at
abnormal test results. very high risk of having precancer has the greatest need of pre-
The National Cancer Institute (NCI) and ASCCP agreed for- ventive treatment; at the highest risk, expedited treatment might
mally in 2017 through a Memorandum of Understanding to em- be preferred without need for colposcopic biopsy. At somewhat
bark on a new set of guidelines.1 Three times before, in 2001,2,3 lower but still high risk, colposcopic biopsies are recommended to
2006,4,5 and 2012,6 the NCI and ASCCP had collaborated in a for- find or rule out precancer requiring treatment. At lower but
mal consensus guidelines process and also helped produce several nonnegligible risk, colposcopy is not needed, but surveillance at
other related guidances. shortened intervals is prudent (1 and 3 years were maintained as
The role of NCI epidemiologists and statisticians who spe- the 2 levels of concern/attention) to reduce the risk of “interval
cialize in cervical screening has been to provide state-of-the-art cancers” occurring before the next testing visit. Women at very
epidemiologic evidence regarding test performance based on NCI low risk provided by a negative human papillomavirus (HPV)
and other research. The role of ASCCP has been to convene and test (or HPV and cytology cotest) are recommended to continue
conduct a consensus process bringing together US clinical organi- screening at the 5-year interval.
zations and other important “stakeholders” to create the guide- Deciding on the clinical action thresholds for each manage-
lines. The objective of the new agreement was to produce clear ment option (treatment preferred, treatment or colposcopic biopsy,
colposcopic biopsy, surveillance retesting at 1 year, surveillance
1
Division of Cancer Epidemiology and Genetics, National Cancer Institute, retesting at 3 years, return at regular screening interval of 5 years)
Rockville, MD; 2Department of Obstetrics and Gynecology, Boston University
School of Medicine, Boston, MA; and 3Department of Obstetrics, Gynecology
required an 18-month collective effort involving the volunteering
and Reproductive Sciences, UPMC Magee-Women's Hospital, Pittsburgh, PA cervical health professionals and patient advocates and including
Reprint requests to: Mark Schiffman, MD, Division of Cancer Epidemiology a period for public input. These societal decisions were acknowl-
and Genetics, National Cancer Institute, National Institutes of Health, 9609 edged to be part of the larger subjective question of “How safe is
Medical Center Dr, Rm 6E544, Rockville, MD 20892. E-mail:
schiffmm@mail.nih.gov
safe enough? What risk levels in our society warrant escalating to
The National Cancer Institute (MS, NW) has received cervical screening test the next, more aggressive clinical actions?”
results and supplies at no cost to conduct independent evaluations of The clinical action thresholds adopted by consensus voting
methods and natural history research. The commercial donors have not in October 2019 after substantial study and discussion are intended
participated in the decision to publish or the content. The other authors
report no conflicts of interest.
to endure, providing stability to the US cervical screening effort,
Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on even as screening test methods and strategies evolve. When a
behalf of the ASCCP. This is an open-access article distributed under the new test is approved by the Food and Drug Administration that
terms of the Creative Commons Attribution-Non Commercial-No Derivatives test can be considered for inclusion in the consensus guidelines
License 4.0 (CCBY-NC-ND), where it is permissible to download and share
the work provided it is properly cited. The work cannot be changed in any
as soon as sufficient data are available to know what risk of precancer
way or used commercially without permission from the journal. is predicted by a positive result versus a negative result. Adequate
DOI: 10.1097/LGT.0000000000000531 prospective data will be necessary before a test can be

Journal of Lower Genital Tract Disease • Volume 24, Number 2, April 2020 87
Schiffman et al. Journal of Lower Genital Tract Disease • Volume 24, Number 2, April 2020

recommended as the basis for surveillance at 1- or 3-year intervals follow-up. An individual patient under management would likely
or return to routine screening at 5-year intervals. Cross-sectional attend more than one of these visits.
data will be needed to supply the immediate risk estimates that It is important to realize that most clinical visits devoted to
support recommendations for treatment or referral to colposcopy. management of abnormal cervical cancer screening results will in-
To give an example, the new consensus is that the clinical action volve common and ultimately benign HPV infections and minor
threshold for referral to colposcopy and biopsies (and possibly cytologic abnormalities. For example, roughly 20% of individuals
treatment) is a 4.0% immediate risk of CIN 3+. Patients with an participating in cotesting for 7 years at KPNC had at least 1 abnor-
underlying immediate risk of CIN 3+ of 4.0% or more are recom- mal result (HPV and/or cytology). The 2019 guidelines address as
mended to have colposcopy whether that risk is due to HPV- many abnormal result combinations as possible, using 2 different
positive ASC-US, HPV-positive low-grade squamous intraepithelial approaches. The common initial visits that are mainly minor ab-
lesion or greater, HPV 16–positive NILM, a posttreatment positive normalities are handled in the 2019 guidelines by use of risk tables
HPV test, or any other set of results predicting equally high risk. and clinical action thresholds.9 At the KPNC, colposcopy referrals
If a positive result from a new triage test for HPV-positive patients leading to postcolposcopy management decisions are about half
is convincingly shown to convey a CIN 3+ risk greater than or as frequent as initial management visits; these are addressed by
equal to 4.0% upon immediate referral to colposcopy, there would both risk tables9 and, for uncommon or especially high-risk situa-
be no need for a new consensus conference to determine how to tions, management algorithm figures.10 Treatment and posttreat-
use that test in clinical practice: the management of a positive re- ment visits are uncommon (approximately 1/10th as frequent as
sult would be to refer to colposcopy (with optional or even pre- initial management visits in the KPNC data set), but are especially
ferred, expedited treatment if risk is sufficiently high). By the important to preventing cancer, and are addressed using a series of
guiding principle of “Equal Management of Equal Risk,” the management algorithm figures.10
guideline would be evident and easily settled. At each management visit after an abnormal screening result,
At the same time that the clinical action thresholds were be- the current test results under consideration, including both screen-
ing considered, the large remaining task was to estimate the risks ing and triage tests, colposcopic biopsy results, recent past screen-
themselves, for the cervical screening test combinations that a cli- ing history, etc depending on the decision point will be used to
nician and patient might encounter together at a management visit find the estimated risk of CIN 3+. Current HPV test results, as
after abnormal screening. In the development of the new guide- the most important prediction factor, is necessary for “precision
lines, it was the responsibility of NCI HPV epidemiologists and management.” However, some other missing data are expected
statisticians to estimate the risks of precancer predicted by the for the risk estimations and were accommodated in the risk tables.
large number of combinations of HPV tests and cytology, and past Increased precision of management guidance will be possible if
screening test and colposcopic biopsy results, and other possibly information is complete, but risk estimates and resultant manage-
important factors. The main source of the risk estimates was ment recommendations can be based on whatever test results in
the unique clinical database from Kaiser Permanente Northern addition to HPV result are available.
California (KPNC), which instituted HPV/cytology cervical The predicted risk of CIN 3+ is determined by referencing an
cotesting at 3-year intervals in their very large membership in extensive risk table compiled by the NCI and accessible on an
2003. The KPNC has uniquely detailed data and follow-up, per- NIH Web site. A comparison of the risk, found for the given pa-
mitting us to observe the risk of CIN 2, CIN 3, AIS, and cancer tient in the risk database, to the Clinical Action Thresholds will
after even unusual combinations of screening test results. yield the recommended course of action. Navigation of the
The generalizability (“portability”) of the estimates from the guidelines can be facilitated by applications on platforms such
KPNC to other US populations at known higher risk of cervical as smartphones or websites, or eventually integrated into lab re-
cancer than KPNC was addressed by research in 4 diverse screen- ports or the electronic medical record. Of note, risk is not cal-
ing programs and trials. A systematic review covering items too culated at the time of use; the precalculated risk for the
uncommon or otherwise not addressed adequately by risk estima- combination of current test results, past screening history, and
tion was also performed.7,8 other factors is found in the tables either manually or by a soft-
Of note, CIN 3+ (including CIN 3 and AIS) was chosen as the ware application. Health decision aids are increasingly familiar
working definition of precancer. Rare cancers found within a screen- in US medical practice. Well-known examples include the
ing program were included as screening targets, recognizing how- FRAX fracture risk assessment tool as well as the Breast Cancer
ever that detection of precancers is the dominant goal of screening Risk Assessment Tool of Gail et al.11,12
in the United States. Cervical intraepithelial neoplasia 2 was consid- The risk database will be kept current, to permit updates of the
ered too variable to serve as a surrogate end point of cancer risk. The guidelines as new methods and prospective follow-up data emerge.
Lower Anogenital Squamous Terminology category of histologic The risks predicted by the new tests can be added to the database,
high-grade squamous intraepithelial lesion could not be highlighted and clinicians can access updates without waiting for a new guide-
because of lack of prospective studies using that terminology. lines meeting. Under the principle of “Equal Management of Equal
Clinical action thresholds were based on estimated risk of Risk,” management recommendations are made regardless of
CIN 3+ at the time of the abnormal screening results (“immediate” which test results and screening history led to that risk level.
risk) for treatment and referral to colposcopic biopsies. For sur-
veillance thresholds, risks at 5 years were emphasized.
CONCLUDING DESCRIPTION OF THE
GUIDELINES ARTICLES
HOW THE NEW APPROACH WILL WORK This introduction is followed by a statistical method paper,13
IN PRACTICE which describes how NCI statisticians developed new methods
Clinicians are likely to consult guidelines in 5 different clin- and applied them to analyze available data to produce the risk ta-
ical situations: consideration of a new abnormal screening result; ble. The main guideline paper10 had input from many sources; the
management of a follow-up test result at a 1- or 3-year surveil- risk-based approach proved adequate for most visits, but some
lance return visit; interpretation of colposcopic biopsy diagnosis; special populations and topics are best handled at this time by
follow-up of postcolposcopy surveillance of patients not initially using management algorithms of the conventional kind, guided
found to need treatment (e.g., a biopsy <CIN 2); and posttreatment by expert opinion. The risk table manuscript,9 mainly derived from

88 © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASCCP.
Journal of Lower Genital Tract Disease • Volume 24, Number 2, April 2020 Management Consensus Guidelines

KPNC, gives the risk estimation data permitting management of most management of abnormal cervical cancer screening tests and cancer
patients. Use of genotyping is addressed separately.14 A literature re- precursors. J Low Genit Tract Dis 2013;17(5 suppl 1):S1–27.
view led by the new technologies working group8 is followed by an 7. Clarke M, Unger ER, Zuna R, et al. A systematic review of tests for
article addressing how quality assessment was used in the literature post-colposcopy and post-treatment surveillance. J Low Genit Tract Dis
review.7 Finally, there is a description15 of the broader US public 2020;24:148–56.
input received in the formulation of the guidelines. 8. Clarke M, Darragh TM, Nelson E, et al. Reporting and assessing the quality
We conclude this introduction with the express hope that the of diagnostic accuracy studies for cervical cancer screening and
revised guidelines improve and simplify the management of cervical management. J Low Genit Tract Dis 2020;24:157–66.
cancer screening abnormalities in the United States. We welcome
suggestions from any reader as to how further improvements 9. Egemen D, Cheung LC, Chen X, et al. Risk estimates supporting the 2019
ASCCP Risk-Based Management Consensus Guidelines. J Low Genit
could be made.
Tract Dis 2020;24:132–43.
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© 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASCCP. 89