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.

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.

The association of initiating HPV vaccination at ages 9-10 years and up-to-date status among adolescents ages 13-17 years, 2016-2020.

Recent guidelines from the American Cancer Society stress HPV vaccination series initiation at the youngest opportunity, i.e., age 9 years. There are limited data on the association between initiating HPV vaccination at ages 9-10 years and up-to-date (UTD) status. In this study, we compare nationally representative UTD HPV vaccination rates between adolescents who initiated the series younger (ages 9-10 years) vs. older (≥ age 11 years). Five years of pooled data (2016-2020) from National Immunization Survey-Teen were used to estimate the UTD HPV vaccination prevalence among younger vs. older initiating 13-17-year-olds. Adjusted logistic regression models estimated prevalence ratios (aPRs), differences (aDs), and difference in differences (aDDs) in prevalence of being UTD to assess the overall association of age at initiation with being UTD and differences in sociodemographic predictors of being UTD among younger vs. older initiators. UTD prevalence for younger initiators was 93% compared with 72% among older initiators (aPR: 1.27,95%CI: 1.24,1.31). Among older initiators, UTD prevalence was significantly different by sex, insurance status, and current age; no such differences were observed among younger initiators. Results indicate that younger initiation is associated with a 27% higher UTD prevalence, highlighting the importance of promoting younger initiation, particularly among those with health-care barriers.

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.

Gaps and Opportunities to Improve Prevention of Human Papillomavirus-Related Cancers.

Human papillomavirus (HPV) infections cause more than 35,900 cancers annually in the United States. Although cervical cancer is the most prevalent HPV-related malignancy in women, the virus is also responsible for a significant percentage of anal, vaginal, and vulvar cancers. A comprehensive approach to mitigating cervical cancer includes HPV vaccination (primary prevention), screening and treatment of precancerous lesions (secondary prevention), and diagnosis and treatment of invasive cancer (tertiary prevention). Although a successful strategy, there are opportunities to innovate and increase access that can also be adapted to address the unique clinical care gaps that exist with the other anogenital cancers. The Society for Women's Health Research held a series of interdisciplinary meetings and events, during which expert researchers, clinicians, patient advocates, and health care policy leaders evaluated the current landscape of HPV-related cancers and their effects on women's health. This report summarizes the discussions of this working group and areas it identified in which to address gaps in primary and secondary prevention approaches to improve access and health outcomes for women with HPV-related anogenital cancers.

Uptake of co-testing with HPV and cytology for cervical screening: A population-based evaluation in the United States.

OBJECTIVES: Human papillomavirus (HPV) testing for cervical screening has been shown to increase the yield of precancerous disease and reduce the incidence of cervical cancer more than cytology alone. Here we document the state-wide uptake of co-testing with HPV and cytology in women aged 30-64 years as recommended by national and international bodies. METHODS: Registry-based study of all screening cytology and HPV tests in New Mexico from 2008 to 2019 among women aged 21-64 years, with a focus on cytology negative tests to distinguish co-testing from reflex HPV testing to triage equivocal or mildly abnormal cytology. RESULTS: A total of 1,704,055 cervical screening tests from 681,440 women aged 21-64 years in the state of New Mexico were identified. The proportion of screening tests which were co-tests rose from 5.6% in 2008 to 84.3% in 2019 among women aged 30-64 years with a marked change from the near exclusive use of the Hybrid Capture II HPV test, (a signal amplified test method) to the use of target amplified HPV tests. The largest increases were seen between 2013 and 2015, reflecting the introduction and adoption of new clinical guidelines. Increases in co-testing were also seen in younger women. CONCLUSIONS: Co-testing is now well established in women aged 30-64 years, but smaller increases have also been seen at younger ages, although this is not currently recommended. The impact of co-testing on cervical disease outcomes and number of colposcopies and biopsies in routine population settings remain important, especially in young women.

School-entry requirements for HPV vaccination: part of the patchwork for HPV-related cancer prevention.

Human papillomavirus (HPV) vaccination can prevent six types of HPV-related cancers, and approximately, 54.2% of adolescents are up-to-date with the HPV vaccine in the United States. While moderate success has been achieved with provider- and parent-focused interventions, HPV vaccination in the U.S. lags well behind desired goals. In order to maximize HPV vaccination and prevention of HPV-related cancers, it may be prudent to consider state policy approaches, such as school-entry requirements as part of the patchwork of provider, parent, and structural interventions. In this paper, we reviewed the history of efforts to implement school-entry requirements for HPV vaccine, the challenges and benefits associated with implementing these requirements, and the evidence for the effectiveness of school-entry requirements. In addition, we presented new data from Rhode Island's Immunization Information System (IIS) showing how their school-entry requirement, implemented in 2015, has impacted HPV vaccination rates. These registry data indicate that HPV vaccination rates improved significantly after the 2014-2015 school year and policy implementation, and add to the ongoing evidence supporting the value of school-entry requirements for HPV vaccination. School-entry requirements should be considered alongside other initiatives and policies for promoting HPV vaccine uptake. Taking a comprehensive systems approach to HPV vaccination is needed.

Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society.

The American Cancer Society (ACS) recommends that individuals with a cervix initiate cervical cancer screening at age 25 years and undergo primary human papillomavirus (HPV) testing every 5 years through age 65 years (preferred); if primary HPV testing is not available, then individuals aged 25 to 65 years should be screened with cotesting (HPV testing in combination with cytology) every 5 years or cytology alone every 3 years (acceptable) (strong recommendation). The ACS recommends that individuals aged >65 years who have no history of cervical intraepithelial neoplasia grade 2 or more severe disease within the past 25 years, and who have documented adequate negative prior screening in the prior 10 years, discontinue all cervical cancer screening (qualified recommendation). These new screening recommendations differ in 4 important respects compared with the 2012 recommendations: 1) The preferred screening strategy is primary HPV testing every 5 years, with cotesting and cytology alone acceptable where access to US Food and Drug Administration-approved primary HPV testing is not yet available; 2) the recommended age to start screening is 25 years rather than 21 years; 3) primary HPV testing, as well as cotesting or cytology alone when primary testing is not available, is recommended starting at age 25 years rather than age 30 years; and 4) the guideline is transitional, ie, options for screening with cotesting or cytology alone are provided but should be phased out once full access to primary HPV testing for cervical cancer screening is available without barriers. Evidence related to other relevant issues was reviewed, and no changes were made to recommendations for screening intervals, age or criteria for screening cessation, screening based on vaccination status, or screening after hysterectomy. Follow-up for individuals who screen positive for HPV and/or cytology should be in accordance with the 2019 American Society for Colposcopy and Cervical Pathology risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors.

Human papillomavirus vaccination 2020 guideline update: American Cancer Society guideline adaptation.

The American Cancer Society (ACS) presents an adaptation of the current Advisory Committee on Immunization Practices recommendations for human papillomavirus (HPV) vaccination. The ACS recommends routine HPV vaccination between ages 9 and 12 years to achieve higher on-time vaccination rates, which will lead to increased numbers of cancers prevented. Health care providers are encouraged to start offering the HPV vaccine series at age 9 or 10 years. Catch-up HPV vaccination is recommended for all persons through age 26 years who are not adequately vaccinated. Providers should inform individuals aged 22 to 26 years who have not been previously vaccinated or who have not completed the series that vaccination at older ages is less effective in lowering cancer risk. Catch-up HPV vaccination is not recommended for adults aged older than 26 years. The ACS does not endorse the 2019 Advisory Committee on Immunization Practices recommendation for shared clinical decision making for some adults aged 27 through 45 years who are not adequately vaccinated because of the low effectiveness and low cancer prevention potential of vaccination in this age group, the burden of decision making on patients and clinicians, and the lack of sufficient guidance on the selection of individuals who might benefit.

Rhode Island Human Papillomavirus Vaccine School Entry Requirement Using Provider-Verified Report.

INTRODUCTION: Human papillomavirus vaccine school entry requirements may be an opportunity to improve the low rates of human papillomavirus vaccination among adolescents. This study evaluates changes in provider-verified human papillomavirus vaccine uptake by age 13 years for adolescents in Rhode Island compared with all other states from 2011 to 2017. METHODS: The National Immunization Survey-Teen 2011-2017, a population-based cross-sectional survey, was analyzed in 2019. The survey included telephone interviews and provider-verified reports of vaccination among U.S. adolescents aged 13-17 years. The sample was subset to participants with provider-verified human papillomavirus vaccination reports (n=145,153). A difference-in-differences approach evaluated the Rhode Island human papillomavirus vaccination school entry requirement enacted in 2015. The main outcome was provider-verified human papillomavirus vaccine uptake by age 13 years. RESULTS: Compared with boys in other states, boys in Rhode Island had an increase of 14 percentage points in the probability of uptake of human papillomavirus vaccination by age 13 years (ß=0.139, 95% CI=0.073, 0.205). No such differences were observed on comparing girls in Rhode Island with girls in other states (ß=0.009, 95% CI= -0.068, 0.086). CONCLUSIONS: The Rhode Island school entry requirement for human papillomavirus vaccination improved rates of vaccine uptake among boys and may be a useful option for improving human papillomavirus vaccination nationally.

Geographic and sociodemographic differences in cervical cancer screening modalities.

Cervical cancer screening recommendations for women aged 30-65 years include co-testing (high-risk human papillomavirus [hrHPV] with Pap testing) every five years or Pap testing alone every three years. Geographic variations of these different screening modalities across the United States have not been examined. We selected 82,426 non-pregnant women aged 30-65 years from the 2016 Behavioral Risk Factor Surveillance System with data on sociodemographics, hysterectomy, and cervical cancer screening, representing 42 states and the District of Columbia. Logistic regression models with predicted marginal probabilities were used to calculate state-level prevalence estimates of recent cervical cancer screening and uptake of co-testing, Pap testing, and hrHPV testing among those who were recently screened. Analysis was conducted in 2018-2019. Recent screening prevalence ranged from 80.0% (Idaho) to 92.2% (Massachusetts), with more state-level geographic variability in co-testing than Pap testing alone. Uptake of co-testing ranged from 27.5% (Utah) to 49.9% (District of Columbia); compared to the national estimate, co-testing was lower in 12 states and higher in six states. Overall, Midwestern and Southern states had the lowest uptake of co-testing whereas Northeastern states had the highest. Sociodemographic, healthcare, and behavioral factors accounted for some but not all state-level variation in co-testing. There was substantial state-level variability in co-testing prevalence, which was lowest in Midwestern and Southern states; the variation was not entirely explained by individual sociodemographic, healthcare, and behavioral factors. Future studies should monitor the impact of geographic variations in screening modalities on state-level differences in cervical cancer incidence, survival, and mortality.

Cancer screening in the United States, 2019: A review of current American Cancer Society guidelines and current issues in cancer screening.

Each year, the American Cancer Society publishes a summary of its guidelines for early cancer detection, data and trends in cancer screening rates, and select issues related to cancer screening. In this issue of the journal, the current American Cancer Society cancer screening guidelines are summarized, and the most current data from the National Health Interview Survey are provided on the utilization of cancer screening for men and women and on the adherence of men and women to multiple recommended screening tests.

Reaching 80% human papillomavirus vaccination prevalence by 2026: How many adolescents need to be vaccinated and what are their characteristics?

BACKGROUND: Human papillomavirus vaccination (HPVV) prevents several types of cancer. The American Cancer Society recently established a goal that by 2026, 80% of adolescents will be up to date (UTD) before their 13th birthday. However, the number in need of vaccination to reach this goal is unknown. This study estimated the number of additional adolescents (11-12 years old) who need HPVV for 80% prevalence to be reached by 2026. METHODS: The study used de-identified and publicly available data and exempt from institutional review board approval and informed consent. The 2016 National Immunization Survey for Teens was used to estimate the baseline HPVV prevalence. Linear growth to 80% HPVV prevalence by 2026 was applied to set intermediate targets. US Census Bureau data were used for population projections. This study estimated the cumulative number of additional adolescents 11 to 12 years old who would need to become UTD (ie, receive 2 doses) by first subtracting the number who would need to be vaccinated to achieve an intermediate target prevalence from the estimated number currently compliant and then summing these numbers between 2018 and 2026. RESULTS: Nationwide, an additional 7.62 million males (95% confidence interval [CI], 6.78 million to 8.40 million) and an additional 6.77 million females (95% CI, 5.95 million to 7.55 million), aged 11 to 12 years, would need to receive 2 doses of the vaccine between 2018 and 2026 for 80% prevalence to be achieved. Most adolescents not UTD (80%) also needed to initiate vaccination, and more than 90% recently visited a health care provider. CONCLUSIONS: It is estimated that at least 14.39 million additional adolescents aged 11 to 12 years in the United States will need to receive 2 doses of HPVV for a UTD HPVV prevalence of 80% to be achieved by 2026. To reach this goal, improvements in facilitators of HPVV initiation, including physician recommendations and parental acceptability, are needed.