Enduring Consensus Guidelines for Cervical Cancer Screening and Management: Introduction to the Scope and Process.

OBJECTIVES: The Enduring Consensus Cervical Cancer Screening and Management Guidelines (Enduring Guidelines) effort is a standing committee to continuously evaluate new technologies and approaches to cervical cancer screening, management, and surveillance. METHODS AND RESULTS: The Enduring Guidelines process will selectively incorporate new technologies and approaches with adequate supportive data to more effectively improve cancer prevention for high-risk individuals and decrease unnecessary procedures in low-risk individuals. This manuscript describes the structure, process, and methods of the Enduring Guidelines effort. Using systematic literature reviews and primary data sources, risk of precancer will be estimated and recommendations will be made based on risk estimates in the context of established risk-based clinical action thresholds. The Enduring Guidelines process will consider health equity and health disparities by assuring inclusion of diverse populations in the evidence review and risk assessment and by developing recommendations that provide a choice of well-validated strategies that can be adapted to different settings. CONCLUSIONS: The Enduring Guidelines process will allow updating existing cervical cancer screening and management guidelines rapidly when new technologies are approved or new scientific evidence becomes available.

Recommendations for Use of p16/Ki67 Dual Stain for Management of Individuals Testing Positive for Human Papillomavirus.

OBJECTIVES: The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for dual stain (DS) testing with CINtec PLUS Cytology for use of DS to triage high-risk human papillomavirus (HPV)-positive results. METHODS: Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated according to DS results among individuals testing HPV-positive using data from the Kaiser Permanente Northern California cohort and the STudying Risk to Improve DisparitiES study in Mississippi. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines. Resource usage metrics were calculated to support decision-making. Risk estimates in relation to clinical action thresholds were reviewed and used as the basis for draft recommendations. After an open comment period, recommendations were finalized and ratified through a vote by the Consensus Stakeholder Group. RESULTS: For triage of positive HPV results from screening with primary HPV testing (with or without genotyping) or with cytology cotesting, colposcopy is recommended for individuals testing DS-positive. One-year follow-up with HPV-based testing is recommended for individuals testing DS-negative, except for HPV16- and HPV18-positive results, or high-grade cytology in cotesting, where immediate colposcopy referral is recommended. Risk estimates were similar between the Kaiser Permanente Northern California and STudying Risk to Improve DisparitiES populations. In general, resource usage metrics suggest that compared with cytology, DS requires fewer colposcopies and detects cervical intraepithelial neoplasia grade 3 or worse earlier. CONCLUSIONS: Dual stain testing with CINtec PLUS Cytology is acceptable for triage of HPV-positive test results. Risk estimates are portable across different populations.

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 human papillomavirus testing alone for patients undergoing observation for cervical intraepithelial neoplasia 2; revision of unsatisfactory cytology management; clarification that 2012 guidelines should be followed for patients aged 25 years and older screened with cytology only; management of patients for whom colposcopy was recommended but not completed; clarification that after treatment for cervical intraepithelial neoplasia 2+, 3 negative human papillomavirus tests or cotests at 6, 18, and 30 months are recommended before the patient can return to a 3-year testing interval; and clarification of postcolposcopy management of minimally abnormal results.

Cervical Cancer Screening: A Review.

Importance: Each year in the US, approximately 100 000 people are treated for cervical precancer, 14 000 people are diagnosed with cervical cancer, and 4000 die of cervical cancer. Observations: Essentially all cervical cancers worldwide are caused by persistent infections with one of 13 carcinogenic human papillomavirus (HPV) genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68. HPV vaccination at ages 9 through 12 years will likely prevent more than 90% of cervical precancers and cancers. In people with a cervix aged 21 through 65 years, cervical cancer is prevented by screening for and treating cervical precancer, defined as high-grade squamous intraepithelial lesions of the cervix. High-grade lesions can progress to cervical cancer if not treated. Cervicovaginal HPV testing is 90% sensitive for detecting precancer. In the general population, the risk of precancer is less than 0.15% over 5 years following a negative HPV test result. Among people with a positive HPV test result, a combination of HPV genotyping and cervical cytology (Papanicolaou testing) can identify the risk of precancer. For people with current precancer risks of less than 4%, repeat HPV testing is recommended in 1, 3, or 5 years depending on 5-year precancer risk. For people with current precancer risks of 4% through 24%, such as those with low-grade cytology test results (atypical squamous cells of undetermined significance [ASC-US] or low-grade squamous intraepithelial lesion [LSIL]) and a positive HPV test of unknown duration, colposcopy is recommended. For patients with precancer risks of less than 25% (eg, cervical intraepithelial neoplasia grade 1 [CIN1] or histologic LSIL), treatment-related adverse effects, including possible association with preterm labor, can be reduced by repeating colposcopy to monitor for precancer and avoiding excisional treatment. For patients with current precancer risks of 25% through 59% (eg, high-grade cytology results of ASC cannot exclude high-grade lesion [ASC-H] or high-grade squamous intraepithelial lesion [HSIL] with positive HPV test results), management consists of colposcopy with biopsy or excisional treatment. For those with current precancer risks of 60% or more, such as patients with HPV-16-positive HSIL, proceeding directly to excisional treatment is preferred, but performing a colposcopy first to confirm the need for excisional treatment is acceptable. Clinical decision support tools can facilitate correct management. Conclusions and Relevance: Approximately 100 000 people are treated for cervical precancer each year in the US to prevent cervical cancer. People with a cervix should be screened with HPV testing, and if HPV-positive, genotyping and cytology testing should be performed to assess the risk of cervical precancer and determine the need for colposcopy or treatment. HPV vaccination in adolescence will likely prevent more than 90% of cervical precancers and cancers.

Management of Abnormal Cervical Cancer Screening Test: A Risk-based Approach.

Cervical cancer screening plays a major role in preventing cervical cancer. The field is based on understanding the natural history of human papillomavirus and its role in cervical cancer. Screening has evolved to assessing the risk for cervical intraepithelial neoplasia grade 3, a true cancer precursor, and performing diagnostic tests based on those risks. This article summarizes the present state of management of abnormal cervical cancer screening tests in the United States, based on the most recent 2019 American Society of Colposcopy and Cervical Pathology guidelines.

Emerging Treatment Options for Cervical Dysplasia and Early Cervical Cancer.

DISCUSSION: of treatment strategies for cervical cancer precursors, review of medical therapies and emerging therapeutics for treatment of cervical cancers, and updates on new approaches to treating early-stage cervical cancers.

Comparison of accuracy and reproducibility of colposcopic impression based on a single image versus a two-minute time series of colposcopic images.

OBJECTIVE: Colposcopy is an important part of cervical screening/management programs. Colposcopic appearance is often classified, for teaching and telemedicine, based on static images that do not reveal the dynamics of acetowhitening. We compared the accuracy and reproducibility of colposcopic impression based on a single image at one minute after application of acetic acid versus a time-series of 17 sequential images over two minutes. METHODS: Approximately 5000 colposcopic examinations conducted with the DYSIS colposcopic system were divided into 10 random sets, each assigned to a separate expert colposcopist. Colposcopists first classified single two-dimensional images at one minute and then a time-series of 17 sequential images as 'normal,' 'indeterminate,' 'high grade,' or 'cancer'. Ratings were compared to histologic diagnoses. Additionally, 5 colposcopists reviewed a subset of 200 single images and 200 time series to estimate intra- and inter-rater reliability. RESULTS: Of 4640 patients with adequate images, only 24.4% were correctly categorized by single image visual assessment (11% of 64 cancers; 31% of 605 CIN3; 22.4% of 558 CIN2; 23.9% of 3412 < CIN2). Individual colposcopist accuracy was low; Youden indices (sensitivity plus specificity minus one) ranged from 0.07 to 0.24. Use of the time-series increased the proportion of images classified as normal, regardless of histology. Intra-rater reliability was substantial (weighted kappa = 0.64); inter-rater reliability was fair ( weighted kappa = 0.26). CONCLUSION: Substantial variation exists in visual assessment of colposcopic images, even when a 17-image time series showing the two-minute process of acetowhitening is presented. We are currently evaluating whether deep-learning image evaluation can assist classification.

Risk-Based Cervical Consensus Guidelines: Methods to Determine Management if Less Than 5 Years of Data Are Available.

OBJECTIVES: In the 2019 ASCCP Risk-Based Management Consensus Guidelines, clinical management decisions are based on immediate and 5-year cervical intraepithelial neoplasia (CIN) 3+ risk estimates. However, data for technologies other than human papillomavirus testing and cytology may be limited to clinical trials and observational studies of shorter duration than 5 years. To enable decisions about 1- or 3-year intervals, 3-year CIN 3+ risk equivalents to 5-year CIN 3+ risk thresholds were generated. MATERIALS AND METHODS: We examined screening test result scenarios around the 5-year risk thresholds of 0.15% and 0.55% and calculated the average percent increase in CIN 3+ risk from 3 to 5 years. Using this average increase, we obtained estimates of corresponding risk thresholds at 3 years. We then validated whether use of the 3-year risk threshold would have resulted in equivalent management per the 2019 recommendations. RESULTS: Around the 5-year CIN 3+ risk threshold of 0.55%, the average increase in risk from 3 to 5 years was 0.16%. Therefore, the equivalent threshold for 3-year risk was estimated as 0.39%. We found no difference in recommendations to return in 1 or 3 years using the 3-year or 5-year risk thresholds in 66 of the 67 scenarios (98.5%) in follow-up in 2019 guidelines. CONCLUSIONS: In this methodological addendum, the Enduring Guidelines Committee adopted the use of the 0.39% 3-year CIN 3+ risk threshold as equivalent of the 0.55% 5-year CIN 3+ risk threshold for technologies with fewer than 5 years of follow-up data. This allows evidence-based guidance for surveillance intervals of 1 or 3 years for new technologies with limited longitudinal data.

Emerging Treatment Options for Fibroids.

Leiomyomas (fibroids) are common, usually benign, monoclonal tumors that arise from the uterine myometrium. Clinical presentation is variable; some patients are asymptomatic, whereas others experience heavy menstrual bleeding, pain, bulk symptoms, and/or alterations in fertility. Previously, treatment options for fibroids were largely surgical. However, over the last decade, options have grown to include many medical and procedural options that allow for uterine and fertility preservation. Clinicians must become familiar with these options to adequately counsel patients desiring treatment of fibroids.

Summary of Current Guidelines for Cervical Cancer Screening and Management of Abnormal Test Results: 2016-2020.

Cervical cancer can be prevented through routine screening and follow-up of abnormal results. Several guidelines have been published in the last 4 years from various medical societies and organizations. These guidelines aim to personalize screening and management, reducing unnecessary testing in low-risk patients and managing high-risk patients with more intensive follow-up. However, the resulting complexity can lead to confusion among providers. The CDC, NCI, and obstetrician-gynecologists involved in guideline development summarized current screening and management guidelines. For screening, guidelines for average-risk and high-risk populations are summarized and presented. For management, differences between the 2012 and 2019 consensus guidelines for managing abnormal cervical cancer screening tests and cancer precursors are summarized. Current screening guidelines for average-risk individuals have minor differences, but are evolving toward an HPV-based strategy. For management, HPV testing is preferred to cytology because it is a more sensitive test for cancer precursor detection and also allows for precise risk stratification. Current risk-based screening and management strategies can improve care by reducing unnecessary tests and procedures in low-risk patients and focusing resources on high-risk patients. Knowledge of screening and management guidelines is important to improve adherence and avoid both over- and under-use of screening and colposcopy.

2019 ASCCP Risk-Based Management Consensus Guidelines: Methods for Risk Estimation, Recommended Management, and Validation.

OBJECTIVE: To manage cervical screening abnormalities, the 2019 ASCCP management consensus guidelines will recommend clinical action on the basis of risk of cervical precancer and cancer. This article details the methods used to estimate risk, to determine the risk-based management, and to validate that the risk-based recommendations are of general use in different settings. METHODS: Based on 1.5 million patients undergoing triennial cervical screening by cotesting at the Kaiser Permanente Northern California from 2003 to 2017, we estimated risk profiles for different clinical scenarios and combinations of past and current human papillomavirus and cytology test results. We validated the recommended management by comparing with the estimated risks in several external data sources. RESULTS: Risk and management tables are presented separately by Egemen et al. and Demarco et al. Risk-based management derived from the Kaiser Permanente Northern California largely agreed with the management implied from the estimated risks of the other data sources. CONCLUSIONS: The new risk-based guidelines present management of abnormal cervical screening results. By describing the steps used to develop these guidelines, the methods presented in this article can provide a basis for future extensions of the risk-based guidelines.

Risk Estimates Supporting the 2019 ASCCP Risk-Based Management Consensus Guidelines.

The 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines for the management of cervical cancer screening abnormalities recommend 1 of 6 clinical actions (treatment, optional treatment or colposcopy/biopsy, colposcopy/biopsy, 1-year surveillance, 3-year surveillance, 5-year return to regular screening) based on the risk of cervical intraepithelial neoplasia grade 3, adenocarcinoma in situ, or cancer (CIN 3+) for the many different combinations of current and recent past screening results. This article supports the main guidelines presentation by presenting and explaining the risk estimates that supported the guidelines. METHODS: From 2003 to 2017 at Kaiser Permanente Northern California (KPNC), 1.5 million individuals aged 25 to 65 years were screened with human papillomavirus (HPV) and cytology cotesting scheduled every 3 years. We estimated immediate and 5-year risks of CIN 3+ for combinations of current test results paired with history of screening test and colposcopy/biopsy results. RESULTS: Risk tables are presented for different clinical scenarios. Examples of important results are highlighted; for example, the risk posed by most current abnormalities is greatly reduced if the prior screening round was HPV-negative. The immediate and 5-year risks of CIN 3+ used to decide clinical management are shown. CONCLUSIONS: The new risk-based guidelines present recommendations for the management of abnormal screening test and histology results; the key risk estimates supporting guidelines are presented in this article. Comprehensive risk estimates are freely available online at https://CervixCa.nlm.nih.gov/RiskTables.

A Study of Partial Human Papillomavirus Genotyping in Support of the 2019 ASCCP Risk-Based Management Consensus Guidelines.

INTRODUCTION: The 2019 ASCCP Risk-Based Management Consensus Guidelines include recommendations for partial human papillomavirus (HPV) genotyping in management of abnormal cervical cancer screening results. The guidelines are based on matching estimates of cervical intraepithelial neoplasia (CIN) 3+ risk to consensus clinical action thresholds. In support of the guidelines, this analysis addresses the risks predicted by individual identification of HPV 16 and HPV 18. METHODS: Risk estimates were drawn from a subset of women in the Kaiser Permanente Northern California screening program, whose residual cervical specimens were HPV typed as part of the HPV Persistence and Progression study. We calculated risk of CIN 3+ to assess how identification of HPV 16, HPV 18, or 12 other "high-risk" HPV types would influence recommended clinical management of new abnormal screening results, taking into account current cytologic results and recent screening history. Immediate and/or 5-year risks of CIN 3+ were matched to clinical actions identified in the guidelines. RESULTS: Identification of HPV 16 at the first visit including HPV testing elevated immediate risk of diagnosing CIN 3+ sufficiently to mandate colposcopic referral even when cytology was Negative for Intraepithelial Lesions or Malignancy and to support a preference for treatment of cytologic high-grade squamous intraepithelial lesion. HPV 18 less clearly elevated CIN 3+ risk. CONCLUSIONS: Identification of HPV 16 clearly mandated consideration in clinical management of new abnormal screening results. HPV 18 positivity must be considered as a special situation because of established disproportionate risk of invasive cancer. More detailed genotyping and use beyond initial management will be considered in guideline updates.

Incorporating Stakeholder Feedback in Guidelines Development for the Management of Abnormal Cervical Cancer Screening Tests.

OBJECTIVE: The 2019 ASCCP Risk-Based Management Consensus Guidelines present a paradigm shift from results- to risk-based management. Patient and provider factors can affect guideline adoption. We sought feedback from stakeholders to inform guideline development. MATERIALS AND METHODS: To solicit provider feedback, we surveyed attendees at the 2019 ASCCP annual meeting regarding readiness to adopt proposed changes and used a web-based public comment period to gauge agreement/disagreement with preliminary guidelines. We elicited patient feedback via a brief survey on preferences around proposed recommendations for treatment without biopsy. Surveys and public comment included both closed-ended and free-text items. Quantitative results were analyzed using descriptive statistics; qualitative results were analyzed using content analysis. Results were incorporated into guideline development in real time. RESULTS: Surveys indicated that 98% of providers currently evaluate their patients' past results to determine management; 88% felt formally incorporating history into management would represent an improvement in care. Most providers supported expedited treatment without biopsy: 22% currently perform expedited treatment and 60% were willing to do so. Among patients, 41% preferred expedited treatment, 32% preferred biopsy before treatment, and the remainder were undecided. Responses from the public comment period included agreement/disagreement with preliminary guidelines, reasons for disagreement, and suggestions for improvement. CONCLUSIONS: Stakeholder feedback was incorporated into the development of the 2019 ASCCP Risk-Based Management Consensus Guidelines. Proposed recommendations with less than two-thirds agreement in the public comment period were considered for revision. Findings underscore the importance of stakeholder feedback in developing guidelines that meet the needs of patients and providers.

Challenges Associated With Cervical Cancer Screening and Management in Obese Women: A Provider Perspective.

OBJECTIVES: Obese women are at increased risk of cervical cancer, partly due to missed detection of cervical precancers during routine cervical cancer screening. We administered a clinician survey to better understand specific challenges and identify potential solutions to performing cervical cancer screening and management in obese women. MATERIALS AND METHODS: We administered a web-based survey to 2,319 members of the American Society of Colposcopy and Cervical Pathology including questions related to challenges associated with cervical sampling and visualization in obese compared with normal weight women and potential strategies for improvement. We summarized providers' responses using descriptive statistics and used Fisher exact tests to evaluate associations between provider characteristics and challenges with cervical sampling, visualization, and biopsy. RESULTS: Of the 240 providers that completed the survey, 89% and 93% reported that cervical sampling and visualization are more challenging in obese women, respectively, whereas 80% reported that taking a biopsy was more challenging. Commonly reported barriers included vaginal prolapse, difficulty visualizing and accessing the cervix, and lack of long enough sampling devices and large enough speculums. Frequently used techniques to improve sampling and visualization included use of a condom or examination glove finger to sheath a speculum and using a tenaculum. Most providers identified training for cervical sampling and colposcopy in obese women as a learning gap, and only 8% reported receiving such training. CONCLUSIONS: Cervical cancer screening and management are more challenging in obese compared with normal weight women. Major barriers to cervical sampling and visualization included lack of adequately sized equipment and lack of education and training.