2019 ASCCP Risk-based Management Consensus Guidelines: updates through 2023

Abstract

This Research Letter summarizes all updates to the 2019 guidelines through September 2023, including: endorsement of the 2021 Opportunistic Infections guidelines for HIV+ or immunosuppressed patients; clarification of use of HPV testing alone for patients undergoing observation for CIN2; revision of unsatisfactory cytology management; clarification that 2012 guidelines should be followed for patients aged ≥ 25 years screened with cytology only; management of patients for whom colposcopy was recommended but not completed; clarification that after treatment for CIN2+, 3 negative HPV tests or co-tests at 6, 18, and 30 months are recommended before the patient can return to a 3-year testing interval; and clarification of post-colposcopy management of minimally abnormal results.

Précis:

The 2019 guidelines were designed to be continuously updated. This letter summarizes updates through 2023.

This report summarizes all updates and corrections to the 2019 ASCCP Risk-based Management Consensus Guidelines (hereafter abbreviated as 2019 guidelines) since publication in April 2020 through September 2023.¹ All changes and corrections to the 2019 Guidelines included here are expected to represent the final report directly linked to the original publication.¹ The updates are summarized in Box 1.

Box 1. Summary of updates to 2019 Guidelines.

Summary of updates to 2019 Guidelines

• Endorsement of the 2021 Opportunistic Infections guidelines for screening and management of HIV+ or immunosuppressed patient.7

• Guidelines were clarified for use of HPV testing alone (primary HPV) for patients undergoing observation for CIN2. Figure 8 was updated to reflect this change.

• Guidelines were revised for repeating an unsatisfactory cytology. Cytology should be repeated as soon as convenient and no later than 4 months.

• Guidelines were clarified around cytology-only screening. For patients 25 and older who are still receiving cytology only screening, 2012 guidelines should be followed.4

• Guidelines were clarified for patients for whom colposcopy was recommended but not completed.4

• Figure 7 from the 2019 guidelines was revised for clarity. After treatment for CIN2+, 3 negative HPV tests or co-tests at 6, 18, and 30 months are recommended before the patient can return to a 3-year testing interval.

• The Legend of Figure 2 from the 2019 guidelines was revised to clarify the algorithm for management after a minimally abnormal screening test result followed by a colposcopy at which high-grade histology was not found.5

Future updates, including guidelines for use of new technologies and updated recommendations related to new risk estimates for established technologies will be developed by the Enduring Consensus Cervical Cancer Screening and Management Guidelines (hereafter abbreviated Enduring Guidelines).² The Enduring Guidelines process is an extension of the 2019 guidelines consensus process, and represents a consensus group representing 20 national organizations, nearly all of which participated in the 2019 guidelines process. Enduring Guidelines updates will be disseminated through full guidelines papers, including a forthcoming methods paper.³

Since the publication of the 2019 guidelines, two types of updates have been required: updates that change recommendations, and updates related to typographical errors or minor wording clarifications. Updates that involve a change in recommendations or a new recommendation were put to a formal vote of the original 2019 committee, which required a 2/3 majority to pass. Minor wording clarifications and typographical errors were corrected and reviewed by co-authors, but not formally voted upon. Between 2020–2021, one recommendation change and one minor clarification were published as Letters to the Editor and/or Errata that are linked to the original 2019 guidelines paper.^4,5 This report summarizes all substantive recommendation updates confirmed by vote (one previously published, three new to this report and not published previously) and several cumulative minor clarifications and corrections.

2019 Guideline substantive recommendations changes and updates

1). Endorsement of the 2021 Opportunistic Infections Guidelines:

The 2019 guidelines endorsed the 2018 “Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV” that were current at the time of publication.⁶ The opportunistic infections guidelines were subsequently updated in 2021.⁷ The updated opportunistic infections guidelines recommend beginning cervical cancer screening at age 21 years, a change from prior guidelines that recommended initiating screening 1 year after sexual debut.

2). Clarification to recommendation statement for patients undergoing observation of CIN2:

The recommendation statement has been updated to clarify that both HPV testing alone and co-testing are acceptable for patients undergoing observation of CIN2. The revised recommendation now states:

Guideline:

For patients with a diagnosis of histologic HSIL (CIN 2) whose concerns about the effects of treatment on a future pregnancy outweigh their concerns about cancer, either observation or treatment is acceptable provided the squamocolumnar junction is fully visualized and CIN 2+ or ungraded CIN is not identified on endocervical sampling (CII) (see Figure 8). If the histologic HSIL cannot be specified as CIN 2, treatment is preferred, but observation is acceptable (CIII). For patients 25 years or older, observation includes colposcopy and HPV-based testing at 6-month intervals for up to 2 years (See Section K.1 of the 2019 guidelinese¹ for management age of younger than 25 years). If during surveillance, all evaluations demonstrate less than CIN 2 histology and either less than ASC-H cytology if using co-testing or HPV-negative if using HPV testing alone on 2 successive occasions, 6 months apart, subsequent surveillance should occur at 1 year after the second evaluation and use HPV-based testing. If negative on 3 consecutive annual surveillance tests, proceed to long-term surveillance (Section J.3 of the 2019 guidelinese¹). If CIN 2 remains present for a 2-year period, treatment is recommended (CII). Note that the original Figure 8 from the 2019 guidelines was updated. The revised Figure 8 in this report replaces the older version and should be used for clinical management.

Figure 8:

Management of CIN2 at age <25 years or for those concerned about the effects of treatment on future pregnancy

3). Update to interval for repeating unsatisfactory cytology:

The recommendation statement has been updated to reflect evidence that waiting two months prior to repeating the cytology test is not necessary.

Guideline:

For patients with an unsatisfactory cytology result and no, unknown, or a negative HPV test result, repeat age-based screening (cytology, cotest, or primary HPV test) as soon as convenient and no later than four months is recommended (BIII).

Rationale:

The 2–4 month waiting period was initially proposed due to early studies indicating differences in cytology results repeated over a short time interval. The recommendation was carried forward through several guideline iterations, but re-review of evidence supports revision of the 2 month waiting period. A seminal paper in 2005 specifically addressed this question, and found the concern of reduced cellularity with short interval repeat not to hold true.⁸ In this study, the cytology interval ranged from 8–30 days in 763 women, 31–60 days in 2317 women, 61–90 days in 1090 women, 91–120 days in 491 women, and 121–184 days in 394 women. They found that repeat cytologic interpretations of unsatisfactory findings, ASC-US, and high-grade squamous intraepithelial lesion (HSIL) did not vary among the Pap interval groups. Most importantly, the approximate cellularity of the samples was slightly better in the interval group of 8–30 days (P trend = 0.04). In addition, higher rates of unsatisfactory results have been documented in patients with cancer compared to those with CIN3 or lower grade results.^9,10 Waiting to repeat an unsatisfactory cytology in the presence of cancer could lead to harm, specifically if other recommended workup for symptomatic patients is not performed. For these reasons, we propose to update the 2019 recommendation.

4). Patient Scenarios Not Initially Addressed in the 2019 Guidelines:

Additional guidance was developed to address scenarios for which the 2019 Guidelines did not initially provide management recommendations. This guidance was voted on in July 2021 and previously published.⁴ To summarize, this guidance (1) outlined management guidelines for cytology results without HPV testing among individuals aged 25 years and older, and (2) clarified management when prior guidelines had not been followed:⁴

1. (1) Guideline for individuals aged 25 and older screened with cytology alone: For individuals aged 25 years or older screened with cytology alone, the 2012 guidelines should be followed. In the 2012 guidelines, colposcopy is recommended for low-grade squamous intraepithelial lesion (LSIL) or a more severe cytologic interpretation.¹¹

2. (2) Guideline for cases in which colposcopy was previously recommended but not completed: In cases in which a colposcopy was previously recommended but not completed, the recommendation is for colposcopy if the prior result was high-grade cytology [atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) atypical glandular cells (AGC), or high grade squamous intraepithelial lesion (HSIL) or a more severe cytologic interpretation]. If the prior cytology result was not high-grade, and the patient undergoes repeat testing with HPV testing or co-testing instead of colposcopy: (a) colposcopy is recommended if the result on repeat testing indicates a second consecutive HPV-positive result and/or persistent cytologic abnormality (atypical squamous cells of uncertain significance, ASC-US, or a more severe cytologic interpretation); (b) repeat HPV testing or co-testing in 1 year is acceptable if the result on repeat testing is HPV negative or co-test negative.

Minor 2019 Guideline updates to correct typographical errors or clarify wording

1). Correction to Figure 7 clarifying that a total of 3 negative HPV-based tests are needed after treatment to return to a 3-year testing interval:

Figure 7:

Management of Histologic HSIL (CIN2 or CIN3 or Not Further Specified)*

The original Figure 7 of the 2019 guidelines was updated. The revised Figure 7 in this report replaces the original Figure 7 and should be used for clinical management. The revised Figure 7 matches the information included in Table 5b of Egemen et al¹² and the text of the guidelines paper which reads: “In patients treated for histologic or cytologic HSIL, after the initial HPV-based test at 6 months, annual HPV or cotesting is preferred until 3 consecutive negative tests have been obtained (AII).”¹ Risk estimates for the 2019 guidelines indicate that, following excisional treatment for histologic HSIL/ CIN2–3, three consecutive negative HPV tests or co-tests are needed at 1-year intervals to identify a group of patients at sufficiently low risk that they can safely return to 3-year testing interval. The 2019 guidelines recommend that the first test occur 6 months following the excisional procedure. Figure 7 erroneously recommended an HPV test or co-test at 6 months followed by 3 consecutive annual HPV or co-tests (a total of 4 consecutive negative tests). This has been corrected to recommend the first HPV test or co-test at 6 months followed by additional HPV or co-tests at 18 months and 30 months. The Figure has also been modified to clarify that follow up should continue at 3-year intervals for a minimum of 25 years and through at least age 65 years and may continue for as long as the patient is in good health.

Prior correction to Figure 2 Legend published October 2020⁵

The Legend for Figure 2 of the original 2019 guidelines paper¹ was updated to clarify the algorithm for management after a minimally abnormal screening test result followed by a colposcopy at which high-grade histology was not found.⁵ The figure legend is repeated here for clarity: “This figure demonstrates how a patient with a common minimally abnormal screening test result (HPV-positive ASC-US) would be managed based on risk estimates. The initial screening result would lead to colposcopy (immediate risk 4.45%). If colposcopy shows less than CIN 2, the 5-year risk is 2.9% (1-year return). At the 1-year return visit, a second HPV-positive ASC-US result has an immediate risk of 3.1% (1-year return). Note similar management would be recommended if the initial abnormality preceding colposcopy were any minimally abnormal test result (i.e., less severe than ASC-H). If the HPV-based test performed for the second post-colposcopy surveillance test is negative, return in 3 years is recommended. If the second post-colposcopy surveillance test results are either a positive HPV test with any cytology result or a negative HPV test result with a cytology result of ASC-H or higher, colposcopy is recommended. Return in 1 year is recommended for HPV-negative ASC-US or LSIL results.”