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.

Attitudes toward the American Cancer Society's 2020 cervical cancer screening guidelines: A qualitative study of a national sample of US clinicians.

BACKGROUND: The 2020 American Cancer Society (ACS) guidelines are the most recent national guidelines for cervical cancer screening. These guidelines propose two major changes from current practice: initiating screening at age 25 years and using primary human papillomavirus (HPV) testing. Adoption of guidelines often occurs slowly, and therefore understanding clinician attitudes is important to facilitate practice change. METHODS: Interviews with a national sample of clinicians who perform cervical cancer screening in a variety of settings explored attitudes toward the two major changes from the 2020 ACS cervical cancer screening guidelines. Clinicians participated in 30- to 60-min interviews exploring their attitudes toward various aspects of cervical cancer screening. Qualitative analysis was performed. RESULTS: Seventy clinicians participated from across the United States. Few respondents were initiating screening at age 25 years, and none were using primary HPV testing. However, over half would be willing to adopt these practices if supported by scientific evidence and recommended by professional medical organizations. Barriers to adoption included the lack of endorsement by professional societies, lack of laboratory availability and insurance coverage, limited autonomy within large health care systems, and concerns related to missed disease. CONCLUSIONS: Few clinicians have adopted screening initiation or primary HPV testing, as recommended by the 2020 ACS guidelines, but over half were open to adopting these changes. Implementation may be facilitated via professional organization endorsement, clinician education, and laboratory, health care system, and insurance support. PLAIN LANGUAGE SUMMARY: In 2020, the American Cancer Society (ACS) released updated guidelines for cervical cancer screening. The main changes to current practices were to initiate screening at age 25 years instead of age 21 years and to screen using primary human papillomavirus (HPV) testing rather than cytology alone or in combination with HPV testing. We performed in-depth interviews with 70 obstetrics and gynecology, family medicine, and internal medicine physicians and advanced practice providers about their attitudes toward these guidelines. Few clinicians are following the 2020 ACS guidelines, but over half were open to changing practice if the changes were supported by evidence and recommended by professional medical organizations. Barriers to adoption included the lack of endorsement by professional medical organizations, logistical issues, and concerns about missed disease.

Factors Associated With Guideline-concordant and Excessive Cervical Cancer Screening: A Mixed Methods Study.

INTRODUCTION: National guidelines recommend cervical cancer screening with Papanicolaou (Pap) testing at 3-year intervals or with human papillomavirus (HPV) testing alone or HPV/Pap cotesting at 5-year intervals for average-risk individuals aged 30-65 years. METHODS: We explored factors associated with clinician-reported guideline-concordant screening, as well as facilitators and barriers to appropriate cervical cancer screening. RESULTS: A national sample of clinicians (N = 1,251) completed surveys; a subset (n = 55) completed interviews. Most (94%) screened average-risk patients aged 30-65 years with cotesting. Nearly all clinicians who were categorized as nonadherent to national guidelines were overscreening (98%). Guideline concordant screening was reported by 47% and 82% of those using cotesting and HPV testing, respectively (5-year intervals), and by 62% of those using Pap testing only (3-year intervals). Concordant screening was reported more often by clinicians who were aged <40 years, non-Hispanic, and practicing in the West or Midwest, and less often by obstetrician-gynecologists and private practice physicians. Concordant screening was facilitated by beliefs that updated guidelines were evidence-based and reduced harms, health care system dissemination of guidelines, and electronic medical record prompts. Barriers to concordant screening included using outdated guidelines, relying on personal judgment, concern about missing cancers, inappropriate patient risk assessment, and lack of support for guideline adoption through health care systems or electronic medical records. CONCLUSIONS: Most clinicians screened with Pap/HPV cotesting and approximately one-half endorsed a 5-year screening interval. Clinician knowledge gaps include understanding the evidence underlying 5-year intervals and appropriate risk assessment to determine which patients should be screened more frequently. Education and tracking systems can promote guideline-concordant screening.

Design of the HPV-automated visual evaluation (PAVE) study: Validating a novel cervical screening strategy.

Background: The HPV-automated visual evaluation (PAVE) Study is an extensive, multinational initiative designed to advance cervical cancer prevention in resource-constrained regions. Cervical cancer disproportionally affects regions with limited access to preventive measures. PAVE aims to assess a novel screening-triage-treatment strategy integrating self-sampled HPV testing, deep-learning-based automated visual evaluation (AVE), and targeted therapies. Methods: Phase 1 efficacy involves screening up to 100,000 women aged 25-49 across nine countries, using self-collected vaginal samples for hierarchical HPV evaluation: HPV16, else HPV18/45, else HPV31/33/35/52/58, else HPV39/51/56/59/68 else negative. HPV-positive individuals undergo further evaluation, including pelvic exams, cervical imaging, and biopsies. AVE algorithms analyze images, assigning risk scores for precancer, validated against histologic high-grade precancer. Phase 1, however, does not integrate AVE results into patient management, contrasting them with local standard care.Phase 2 effectiveness focuses on deploying AVE software and HPV genotype data in real-time clinical decision-making, evaluating feasibility, acceptability, cost-effectiveness, and health communication of the PAVE strategy in practice. Results: Currently, sites have commenced fieldwork, and conclusive results are pending. Conclusions: The study aspires to validate a screen-triage-treat protocol utilizing innovative biomarkers to deliver an accurate, feasible, and cost-effective strategy for cervical cancer prevention in resource-limited areas. Should the study validate PAVE, its broader implementation could be recommended, potentially expanding cervical cancer prevention worldwide. Funding: The consortial sites are responsible for their own study costs. Research equipment and supplies, and the NCI-affiliated staff are funded by the National Cancer Institute Intramural Research Program including supplemental funding from the Cancer Cures Moonshot Initiative. No commercial support was obtained. Brian Befano was supported by NCI/ NIH under Grant T32CA09168.

Artificial intelligence-based image analysis in clinical testing: lessons from cervical cancer screening.

Novel screening and diagnostic tests based on artificial intelligence (AI) image recognition algorithms are proliferating. Some initial reports claim outstanding accuracy followed by disappointing lack of confirmation, including our own early work on cervical screening. This is a presentation of lessons learned, organized as a conceptual step-by-step approach to bridge the gap between the creation of an AI algorithm and clinical efficacy. The first fundamental principle is specifying rigorously what the algorithm is designed to identify and what the test is intended to measure (eg, screening, diagnostic, or prognostic). Second, designing the AI algorithm to minimize the most clinically important errors. For example, many equivocal cervical images cannot yet be labeled because the borderline between cases and controls is blurred. To avoid a misclassified case-control dichotomy, we have isolated the equivocal cases and formally included an intermediate, indeterminate class (severity order of classes: case>indeterminate>control). The third principle is evaluating AI algorithms like any other test, using clinical epidemiologic criteria. Repeatability of the algorithm at the borderline, for indeterminate images, has proven extremely informative. Distinguishing between internal and external validation is also essential. Linking the AI algorithm results to clinical risk estimation is the fourth principle. Absolute risk (not relative) is the critical metric for translating a test result into clinical use. Finally, generating risk-based guidelines for clinical use that match local resources and priorities is the last principle in our approach. We are particularly interested in applications to lower-resource settings to address health disparities. We note that similar principles apply to other domains of AI-based image analysis for medical diagnostic testing.

Screening for lung cancer: 2023 guideline update from the American Cancer Society.

Lung cancer is the leading cause of mortality and person-years of life lost from cancer among US men and women. Early detection has been shown to be associated with reduced lung cancer mortality. Our objective was to update the American Cancer Society (ACS) 2013 lung cancer screening (LCS) guideline for adults at high risk for lung cancer. The guideline is intended to provide guidance for screening to health care providers and their patients who are at high risk for lung cancer due to a history of smoking. The ACS Guideline Development Group (GDG) utilized a systematic review of the LCS literature commissioned for the US Preventive Services Task Force 2021 LCS recommendation update; a second systematic review of lung cancer risk associated with years since quitting smoking (YSQ); literature published since 2021; two Cancer Intervention and Surveillance Modeling Network-validated lung cancer models to assess the benefits and harms of screening; an epidemiologic and modeling analysis examining the effect of YSQ and aging on lung cancer risk; and an updated analysis of benefit-to-radiation-risk ratios from LCS and follow-up examinations. The GDG also examined disease burden data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program. Formulation of recommendations was based on the quality of the evidence and judgment (incorporating values and preferences) about the balance of benefits and harms. The GDG judged that the overall evidence was moderate and sufficient to support a strong recommendation for screening individuals who meet the eligibility criteria. LCS in men and women aged 50-80 years is associated with a reduction in lung cancer deaths across a range of study designs, and inferential evidence supports LCS for men and women older than 80 years who are in good health. The ACS recommends annual LCS with low-dose computed tomography for asymptomatic individuals aged 50-80 years who currently smoke or formerly smoked and have a ≥20 pack-year smoking history (strong recommendation, moderate quality of evidence). Before the decision is made to initiate LCS, individuals should engage in a shared decision-making discussion with a qualified health professional. For individuals who formerly smoked, the number of YSQ is not an eligibility criterion to begin or to stop screening. Individuals who currently smoke should receive counseling to quit and be connected to cessation resources. Individuals with comorbid conditions that substantially limit life expectancy should not be screened. These recommendations should be considered by health care providers and adults at high risk for lung cancer in discussions about LCS. If fully implemented, these recommendations have a high likelihood of significantly reducing death and suffering from lung cancer in the United States.

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.

Design of the HPV-Automated Visual Evaluation (PAVE) Study: Validating a Novel Cervical Screening Strategy.

Objective: To describe the HPV-Automated Visual Evaluation (PAVE) Study, an international, multi-centric study designed to evaluate a novel cervical screen-triage-treat strategy for resource-limited settings as part of a global strategy to reduce cervical cancer burden. The PAVE strategy involves: 1) screening with self-sampled HPV testing; 2) triage of HPV-positive participants with a combination of extended genotyping and visual evaluation of the cervix assisted by deep-learning-based automated visual evaluation (AVE); and 3) treatment with thermal ablation or excision (Large Loop Excision of the Transformation Zone). The PAVE study has two phases: efficacy (2023-2024) and effectiveness (planned to begin in 2024-2025). The efficacy phase aims to refine and validate the screen-triage portion of the protocol. The effectiveness phase will examine acceptability and feasibility of the PAVE strategy into clinical practice, cost-effectiveness, and health communication within the PAVE sites. Study design: Phase 1 Efficacy: Around 100,000 nonpregnant women, aged 25-49 years, without prior hysterectomy, and irrespective of HIV status, are being screened at nine study sites in resource-limited settings. Eligible and consenting participants perform self-collection of vaginal specimens for HPV testing using a FLOQSwab (Copan). Swabs are transported dry and undergo testing for HPV using a newly-redesigned isothermal DNA amplification HPV test (ScreenFire HPV RS), which has been designed to provide HPV genotyping by hierarchical risk groups: HPV16, else HPV18/45, else HPV31/33/35/52/58, else HPV39/51/56/59/68. HPV-negative individuals are considered negative for precancer/cancer and do not undergo further testing. HPV-positive individuals undergo pelvic examination with collection of cervical images and targeted biopsies of all acetowhite areas or endocervical sampling in the absence of visible lesions. Accuracy of histology diagnosis is evaluated across all sites. Cervical images are used to refine a deep learning AVE algorithm that classifies images as normal, indeterminate, or precancer+. AVE classifications are validated against the histologic endpoint of high-grade precancer determined by biopsy. The combination of HPV genotype and AVE classification is used to generate a risk score that corresponds to the risk of precancer (lower, medium, high, highest). During the efficacy phase, clinicians and patients within the PAVE sites will receive HPV testing results but not AVE results or risk scores. Treatment during the efficacy phase will be performed per local standard of care: positive Visual Inspection with Acetic Acid impression, high-grade colposcopic impression or CIN2+ on colposcopic biopsy, HPV positivity, or HPV 16,18/45 positivity. Follow up of triage negative patients and post treatment will follow standard of care protocols. The sensitivity of the PAVE strategy for detection of precancer will be compared to current SOC at a given level of specificity.Phase 2 Effectiveness: The AVE software will be downloaded to the new dedicated image analysis and thermal ablation devices (Liger Iris) into which the HPV genotype information can be entered to provide risk HPV-AVE risk scores for precancer to clinicians in real time. The effectiveness phase will examine clinician use of the PAVE strategy in practice, including feasibility and acceptability for clinicians and patients, cost-effectiveness, and health communication within the PAVE sites. Conclusion: The goal of the PAVE study is to validate a screen-triage-treat protocol using novel biomarkers to provide an accurate, feasible, cost-effective strategy for cervical cancer prevention in resource-limited settings. If validated, implementation of PAVE at larger scale can be encouraged. Funding: The consortial sites are responsible for their own study costs. Research equipment and supplies, and the NCI-affiliated staff are funded by the National Cancer Institute Intramural Research Program including supplemental funding from the Cancer Cures Moonshot Initiative. No commercial support was obtained. Brian Befano was supported by NCI/NIH under Grant T32CA09168. Date of protocol latest review: September 24 th 2023.

Examining the association of clinician characteristics with perceived changes in cervical cancer screening and colposcopy practice during the COVID-19 pandemic: a mixed methods assessment.

Background: The COVID-19 pandemic led to reductions in cervical cancer screening and colposcopy. Therefore, in this mixed method study we explored perceived pandemic-related practice changes to cervical cancer screenings and colposcopies. Methods: In 2021, a national sample of 1251 clinicians completed surveys, including 675 clinicians who performed colposcopy; a subset (n=55) of clinicians completed qualitative interviews. Results: Nearly half of all clinicians reported they were currently performing fewer cervical cancer screenings (47%) and colposcopies (44% of those who perform the procedure) than before the pandemic. About one-fifth (18.6%) of colposcopists reported performing fewer LEEPs than prior to the pandemic. Binomial regression analyses indicated that older, as well as internal medicine and family medicine clinicians (compared to OB-GYNs), and those practicing in community health centers (compared to private practice) had higher odds of reporting reduced screening. Among colposcopists, internal medicine physicians and those practicing in community health centers had higher odds of reporting reduced colposcopies. Qualitative interviews highlighted pandemic-related care disruptions and lack of tracking systems to identify overdue screenings. Conclusions: Reductions in cervical cancer screening and colposcopy among nearly half of clinicians more than 1 year into the pandemic raise concerns that inadequate screening and follow-up will lead to future increases in preventable cancers. Funding: This study was funded by the American Cancer Society, who had no role in the study's design, conduct, or reporting.

Electronic data review, client reminders, and expanded clinic hours for improving cervical cancer screening rates after the COVID-19 pandemic shutdowns: A multicomponent quality improvement program.

Background: To improve cervical cancer screening (CCS) rates, the East Boston Neighborhood Health Center implemented a quality improvement initiative from March to August 2021. Methods: Staff training was provided. A 21-provider team validated overdue CCS indicated by electronic medical record data. To improve screening, CCS-only sessions were created during regular clinic hours (n = 5) and weekends/evenings (n = 8). Patients were surveyed on their experience. Results: A total of 6126 charts were reviewed. Of the list of overdue patients, outreach was performed on 1375 patients to schedule the 13 sessions. A total of 459 (33%) patients completed screening, 622 (45%) could not be reached, and 203 (15%) canceled or missed appointments. The proportion of total active patients who were up to date with CCS increased from 68% in March to 73% in August 2021. Survey results indicated high patient satisfaction, and only 42% of patients would have scheduled CCS without outreach. Conclusions: The creation of a validated patient chart list and extra clinical sessions devoted entirely to CCS improved up-to-date CCS rates. However, high rates of unsuccessful outreach and cancelations limited sustainability. This information can be used by other community health centers to optimize clinical workflows for CCS. Funding: All funding was internal from the EBNHC Adult Medicine, Family Medicine, and Women's Health Departments.

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.

Deciphering Knowledge and Opinions of Human Papillomavirus and Human Papillomavirus Vaccination for Facilitation of Point-of-Care Vaccination in Adults.

Importance: Human papillomavirus (HPV) vaccination rates remain significantly below rates for other common childhood vaccines, which has implications for future rates of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Objective: To assess whether individuals who were aware of the association between HPV and OPSCC would be more likely to have been previously vaccinated. Design, Setting, and Participants: This survey study included patients aged 18 to 45 years who sought routine outpatient care at the otolaryngology clinic at Boston Medical Center from September 1, 2020, to May 19, 2021. A survey (HPV-Associated Head and Neck Cancer Epidemiology, Awareness and Demographics) [HEAD]) composed of validated questions to assess patient knowledge of HPV and HPV vaccination and barriers to vaccination was delivered to participants. The survey was paired with a novel point-of-care vaccination program housed within an otolaryngology department. Main Outcomes and Measures: The main outcome was prevalence of knowledge of the relationship between HPV infection and OPSCC based on survey responses. The association of knowledge of HPV-associated OPSCC with likelihood of having been vaccinated was assessed in the overall cohort and by demographic characteristics using multivariate logistic regression. Results: Of 405 patients given the survey, 288 (71.1%) responded. Of these patients, 271 (94.1%) had surveys included; 158 (58.3%) were female, and median age was 29 years (IQR, 24-35 years). The baseline vaccination rate in the surveyed population was low (26.6%; n = 72) overall (10.6% among men [12 of 113]; 37.9% among women [60 of 158]). Few participants understood the relationship between HPV infection and OPSCC (63 of 271 [23.3%]) or that HPV-associated OPSCC is the most common HPV-associated cancer type (9 of 121 [7.4%]). Compared with men, women were more likely to have been previously vaccinated (odds ratio [OR], 6.5; 95% CI, 3.0-13.9), more aware that HPV causes cancer (OR, 3.7; 95% CI, 1.9-7.1), and more likely to have heard about HPV and HPV vaccination from their health care practitioner (OR, 2.6; 95% CI, 1.2-5.7). Knowledge of the relationship between HPV infection and cancer and between HPV and OPSCC was associated with increased likelihood of having been vaccinated (HPV and cancer: OR, 4.1 [95% CI, 1.8-9.5]; HPV and OPSCC: OR, 3.7 [95% CI, 1.8-7.6]). Among 156 unvaccinated participants, 12 of 98 men (12.2%) and 7 of 131 women (5.3%) received point-of-care vaccination. Conclusions: Most participants in this survey study were unaware that HPV causes OPSCC. Understanding that HPV causes OPSCC was associated with increased likelihood of having been vaccinated. However, most patients surveyed were not informed of this relationship by their health care practitioners. Targeted education aimed at unvaccinated adults establishing the relationship between HPV infection and OPSCC, paired with point-of-care vaccination, may be an innovative strategy for increasing HPV vaccination rates in adults.

The combined finding of HPV 16, 18, or 45 and cytologic Atypical Glandular Cells (AGC) indicates a greatly elevated risk of in situ and invasive cervical adenocarcinoma.

BACKGROUND: Cervical screening has not effectively controlled cervical adenocarcinoma (AC). Human papillomavirus (HPV) testing is recommended for cervical screening but the optimal management of HPV-positive individuals to prevent AC remains a question. Cytology and HPV typing are two triage options to predict the risk of AC. We combined two potential biomarkers (atypical glandular cell, AGC, cytology and HPV-types 16, 18, or 45) to assess their joint effect on detecting AC. METHODS: Kaiser Permanente Northern California (KPNC) used triennial co-testing with cytology and HPV testing (positive/negative) for routine cervical screening between 2003 and 2020. HPV typing of a sample of residual HPV test specimens was performed on a separate cohort selected from KPNC (Persistence and Progression, PaP, cohort). We compared risk of prevalent and incident histologic AC/AIS (adenocarcinoma in situ) associated with preceding combinations of cytologic results and HPV typing. Risk of squamous cell cancer (SCC)/cervical intraepithelial neoplasia grade 3 (CIN3) (SCC/CIN3) was also included for comparison. RESULTS: Among HPV-positive individuals in PaP cohort, 99% of prevalent AC and 96% of AIS were linked to HPV-types 16, 18, or 45 (denoted HPV 16/18/45). Although rare (0.09% of screening population), the concurrent detection of HPV 16/18/45 with AGC cytology predicted a highly elevated relative risk of underlying histologic AC/AIS; the absolute risk of diagnosing AC/AIS was 12% and odds ratio (OR) was 1341 (95%CI:495-3630) compared to patients with other high-risk HPV types and normal cytology. Cumulatively (allowing non-concurrent results), approximately one-third of the AC/AIS cases ever had HPV 16/18/45 and AGC cytology (OR = 1785; 95%CI:872-3656). AGC was not as strongly associated with SCC/CIN3. CONCLUSION: Detection of HPV 16/18/45 positivity elevates risk of adenocarcinoma, particularly if AGC cytology is also found.

A cross-sectional survey examining clinician characteristics, practices, and attitudes associated with adoption of the 2019 American Society for Colposcopy and Cervical Pathology risk-based management consensus guidelines.

BACKGROUND: The 2019 American Society for Colposcopy and Cervical Pathology (ASCCP) risk-based management consensus guidelines are the most recent national guidelines for the management of abnormal cervical cancer screening tests. These guidelines benefit patients by concentrating testing and treatment in those at highest cervical cancer risk. Adoption of guidelines often occurs slowly, with few studies examining the factors associated with guideline-adherent management of abnormal results. METHODS: To elucidate the factors associated with the use of the 2019 ASCCP guidelines among clinicians who perform cervical cancer screening, physicians and advanced practice professionals who perform cervical cancer screening were cross-sectionally surveyed. Clinicians responded to screening vignettes with differing recommendations for management between the 2019 and prior management guidelines. Screening vignette 1 involved reduction of invasive testing on a low-risk patient; screening vignette 2 involved increased surveillance testing on a high-risk patient. Binomial logistic regression models determined the factors associated with the use of the 2019 guidelines. RESULTS: A total of 1251 clinicians participated from across the United States. For screening vignettes 1 and 2, guideline-adherent responses were given by 28% and 36% of participants, respectively. Management recommendations differed by specialty and were incorrect in different situations: there was inappropriate invasive testing by obstetrics and gynecology physicians (vignette 1) and inappropriate discontinuation of screening by family and internal medicine physicians (vignette 2). Regardless of their chosen response, over half erroneously believed they were guideline adherent. CONCLUSIONS: Many clinicians who believe they are following appropriate guidelines may not realize their management strategy is inconsistent with the 2019 guidelines. Education initiatives tailored to clinician specialty could address the understanding of current guidelines, encourage the use of updated guidelines, maximize patient benefits, and minimize harms. PLAIN LANGUAGE SUMMARY: The 2019 American Society for Colposcopy and Cervical Pathology risk-based management consensus guidelines are the most recent national guidelines for abnormal cervical cancer screening test management. We surveyed over 1200 obstetrics and gynecology (OB/GYN), family medicine, and internal medicine physicians and advanced practice providers about their screening and abnormal results follow-up practices in relation to guidelines. Few clinicians are following the 2019 guidelines. Management recommendations differed by clinician specialty and were incorrect in different situations: there was inappropriate invasive testing by OB/GYN physicians and inappropriate screening discontinuation by family and internal medicine physicians. Education tailored by clinician specialty could address the understanding of current guidelines, encourage the use of updated guidelines, maximize patient benefits, and minimize harms.

Human papillomavirus vaccination at the first opportunity: An overview.

The Advisory Committee on Immunization Practices (ACIP) has recommended human papillomavirus (HPV) vaccination for adolescents in the United States since 2006. Though recommended at a similar time to the routine recommendations for adolescent tetanus, diphtheria, and acellular pertussis vaccination (Tdap) and quadrivalent meningococcal vaccination (MCV4), HPV vaccine uptake has consistently lagged behind these other adolescent vaccines. The ACIP recommends HPV vaccination at 11-12 y, with vaccination starting at 9 y of age included as an option that is routinely encouraged by the American Academy of Pediatrics and American Cancer Society. To support efforts to increase HPV vaccination at the first opportunity, this commentary summarizes the current HPV vaccination recommendations and available evidence regarding HPV vaccination starting at 9 y - including recent studies and trials documenting the effectiveness of HPV vaccination at 9 in supporting vaccine series completion, while providing future directions for research and implementation to improve HPV vaccination.

Use of risk-based cervical screening programs in resource-limited settings.

Cervical cancer screening and management in the U.S. has adopted a risk-based approach. However, the majority of cervical cancer cases and deaths occur in resource-limited settings, where screening and management are not widely available. We describe a conceptual model that optimizes cervical cancer screening and management in resource-limited settings by utilizing a risk-based approach. The principles of risk-based screening and management in resource limited settings include (1) ensure that the screening method effectively separates low-risk from high-risk patients; (2) directing resources to populations at the highest cancer risk; (3) screen using HPV testing via self-sampling; (4) utilize HPV genotyping to improve risk stratification and better determine who will benefit from treatment, and (5) automated visual evaluation with artificial intelligence may further improve risk stratification. Risk-based screening and management in resource limited settings can optimize prevention by focusing triage and treatment resources on the highest risk patients while minimizing interventions in lower risk patients.