Mona Saraiya

In the United States, the Food and Drug Administration (FDA) is the regulatory authority with the responsibility to evaluate scientific data included in each vaccine’s prescribing information (e.g., safety, indication(s) for use, and dosing schedule) based on several factors, including safety, quality, potency, and effectiveness in preventing disease to assess benefit/risk prior to approval. After approval, the FDA continues to work with sponsors to ensure safety and effectiveness data in the prescribing information remain current. In conjunction with FDA approval or authorization, the Advisory Committee on Immunization Practices (ACIP) recommends immunization dosing schedules and target populations for use. ACIP recommendations that are adopted by the Centers for Disease Control and Prevention (CDC) Director inform national immunization schedules, which influence immunization access, coverage, and provider behavior. This targeted review aims to explore historical instances when vaccine dosing regimens approved by the FDA differ from those recommended by the ACIP, focusing on the frequency and factors behind these differences to inform future ACIP recommendations. Out of n = 78 vaccines assessed, the analysis identified n = 5 vaccines with deviations and only one that reduced dosing. Deviations from the FDA label were determined to be a rare occurrence and are most frequently observed to be additive, not reductive.

Purpose We estimated up-to-date state- and territory-level hysterectomy prevalence and trends, which can help correct the population at risk denominator and calculate more accurate uterine and cervical cancer rates. Methods We analyzed self-reported data for a population-based sample of 1,267,013 U.S. women aged ≥ 18 years who participated in the Behavioral Risk Factor Surveillance System surveys from 2012 to 2020. Estimates were age-standardized and stratified by sociodemographic characteristics and geography. Trends were assessed by testing for any differences in hysterectomy prevalence across years. Results Hysterectomy prevalence was highest among women aged 70–79 years (46.7%) and ≥ 80 years (48.8%). Prevalence was also higher among women who were non-Hispanic (NH) Black (21.3%), NH American Indian and Alaska Native (21.1%), and from the South (21.1%). Hysterectomy prevalence declined by 1.9 percentage points from 18.9% in 2012 to 17.0% in 2020. Conclusions Approximately one in five U.S. women overall and half of U.S. women aged ≥ 70 years reported undergoing a hysterectomy. Our findings reveal large variations in hysterectomy prevalence within and between each of the four census regions and by race and other sociodemographic characteristics, underscoring the importance of adjusting epidemiologic measures of uterine and cervical cancers for hysterectomy status.

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.

Cervical cancer is highly preventable when precancerous lesions are detected early and appropriately managed. However, the complexity of and frequent updates to existing evidence-based clinical guidelines make it challenging for clinicians to stay abreast of the latest recommendations. In addition, limited availability and accessibility to information technology (IT) decision supports make it difficult for groups who are medically underserved to receive screening or receive the appropriate follow-up care. The Centers for Disease Control and Prevention (CDC), Division of Cancer Prevention and Control (DCPC), is leading a multiyear initiative to develop computer-interpretable (“computable”) version of already existing evidence-based guidelines to support clinician awareness and adoption of the most up-to-date cervical cancer screening and management guidelines. DCPC is collaborating with the MITRE Corporation, leading scientists from the National Cancer Institute, and other CDC subject matter experts to translate existing narrative guidelines into computable format and develop clinical decision support tools for integration into health IT systems such as electronic health records with the ultimate goal of improving patient outcomes and decreasing disparities in cervical cancer outcomes among populations that are medically underserved. This initiative meets the challenges and opportunities highlighted by the President's Cancer Panel and the President's Cancer Moonshot 2.0 to nearly eliminate cervical cancer.

Racial and ethnic variations in attribution of cervical precancer and cancer to human papillomavirus (HPV) types may result in different HPV vaccine protection, screening test coverage, and clinical management. Pooling data from 7 US studies, we calculated the proportional attribution of precancers and cancers to HPV types using HPV DNA typing from diagnosis. All statistical tests were 2-sided. For all racial and ethnic groups, most cases of cervical intraepithelial neoplasia grade 3 (CIN3) (84.2%-90.8% of 5526) and squamous cell carcinoma (SCC) (90.4%-93.8% of 1138) were attributed to types targeted by the 9-valent vaccine. A higher proportion of CIN3s were attributed to nonvaccine HPV types among non-Hispanic Black women (15.8%) compared with non-Hispanic Asian or Pacific Islander (9.7%; P = .002), non-Hispanic White (9.2%; P < .001), and Hispanic (11.3%; P = .004) women. The proportion of SCCs attributed to 9-valent types was similar by race and ethnicity (P = .80). A higher proportion of CIN3s were attributed to nonvaccine HPV35 among non-Hispanic Black (9.0%) compared with non-Hispanic Asian or Pacific Islander (2.2%), non-Hispanic White (2.5%), and Hispanic (3.0%; all P < .001) women. Compared with CIN3, the proportion of SCCs attributed to HPV35 among non-Hispanic Black women (3.2%) was lower and closer to other groups (0.3%-2.1%; P = .70). The 9-valent HPV vaccine will prevent nearly all cervical precancers and invasive cancers among major racial and ethnic groups in the United States. Adding HPV35 to vaccines could prevent a small percentage of CIN3s and SCCs, with greater potential impact for CIN3s among Black women. HPV screening tests target high-risk HPV types, including HPV35. Future genotyping triage strategies could consider the importance of HPV35- and other HPV16-related types.