The World Health Organization (WHO) has clearly published the necessary metrics for elimination of cervical cancer as a public health problem, which includes adequate treatment of both cervical cancer and its precursors for at least 90 % of affected individuals. To improve cervical cancer outcomes, universal access to the best surgical procedures, radiation therapy including brachytherapy, and systemic therapy as well as palliative care and end-of-life care is paramount. Although implementation at the state and regional levels can be impactful, providing uniform high-quality treatment throughout the United States is needed to achieve the WHO goal. This manuscript defines broadly acceptable minimum standards of care which need to be funded with closed loopholes for access and payment to achieve eradication of cervical cancer as a public health problem.

Objectives Sexual gender minority (SGM) populations are at risk for human papillomavirus (HPV)–related cancers of the anogenital tract and oropharynx and often face barriers to health care. The goals of this document are to clarify language to provide inclusive care for SGM populations and to provide recommendations for screening and prevention of HPV-related cancers in SGM populations. Materials and Methods An expert committee convened by the American Society for Colposcopy and Cervical Pathology performed a narrative review of the literature through February 2023. A comprehensive MEDLINE database search was performed for relevant studies. The literature review was divided into categories by organ/topic and by SGM population. Given the variability in available data for several of the categories, recommendations were made based on national guidelines where appropriate or expert opinion where there were less data to support risk-based guidelines. Results Definitions and terminology relevant to SGM populations are presented. The authors advocate the adoption of sexual orientation gender identity data collection and an organ-based screening approach, which is possible with knowledge of patient anatomy, sexual behaviors, and clinical history. This includes screening for cervical cancer per national recommendations, as well as screening for anal, vulvar, vaginal, penile, and oral cancers based on risk factors and shared clinical decision making. The authors recommend consideration of HPV vaccination in all SGM individuals up to age 45 years old who are at risk. Conclusions An organ-based screening approach is part of a global strategy to create an inclusive care environment and mitigate barriers to screening and prevention of HPV-mediated cancers in SGM populations.

In July 2020, the American Cancer Society (ACS) released an updated cervical cancer screening guideline calling for primary human papillomavirus (HPV) screening as the preferred strategy.1 Primary HPV screening refers to cervical cancer screening with an HPV test alone as the initial screening modality. Under this strategy, cervical cytology is reserved for use as one option for a triage test should the HPV test result be positive. The scientific data supporting this recommendation have been reviewed both in the United States and in other countries that have transitioned to primary HPV screening.2, 3 The Primary HPV Screening Initiative (PHSI), nested under the ACS National Roundtable on Cervical Cancer, is a national consortium supported by the ACS that convenes key partners and experts on six workgroups and a Steering Committee charged with identifying critical barriers and opportunities for transitioning to primary HPV screening. The workgroups engage approximately 100 volunteers who began their activities in the fall of 2021. Workgroup members are multiprofessional and include leaders in health care policy, health care delivery, and patient care as well as patient advocates. The project is overseen by a Steering Committee (Figure 1) made up of the co-chairs of each of the six workgroups and other experts identified for their leadership in the areas of cervical cancer screening and health care policy. The final deliverable is an implementation report (roadmap), complete with tools and recommendations to support health systems, laboratories, providers, patients, and payors as they make this transition. Initiative workgroup structure. IT/EHR indicates information technology/electronic health record. The Provider Needs Workgroup is developing resources in a variety of formats both to educate providers and to help them educate their patients about the benefits and safety of primary HPV screening. The deliverables include tools to aid in the management of patients with abnormal screening results. Success will be defined by change in provider behavior and will depend in large part on the degree to which major professional organizations (e.g., American College of Obstetricians and Gynecologists, American Academy of Family Physicians, Nurse Practitioners in Women's Health, and American Society for Colposcopy and Cervical Pathology) promote primary HPV screening as the standard for excellent care. The US Preventive Services Task Force recommends primary HPV screening as one of three strategies to screen for cervical cancer starting at age 30 years but does not give preference to modality.4 As of this writing, updated recommendations from the US Preventive Services Task Force are pending. It is desirable that all organizations agree on preferred screening guidelines to facilitate prevention efforts that are supported by evidence and widely accessible. Providers are most likely to follow guidelines promoted by their professional societies, so they are the audience of many of this workgroup's deliverables. Currently, there appears to be limited and variable understanding among many stakeholders regarding why primary HPV screening is better than cotesting. Primary HPV screening has been shown to be more effective than screening with cytology alone and performs similarly to and with lower costs than screening with cotesting.5 Transitioning laboratories to support the changes needed to implement primary HPV screening in the United States is a major yet necessary undertaking. For many laboratories that do not have a US Food and Drug Administration-approved primary HPV screening platform, the logistics of changes in instrumentation, specimen workflow, implementation of newly approved tests for triage of HPV-positive cases, modification of existing quality-assurance/accreditation requirements for cytology-based testing, and impact on the cytologist workforce all need careful consideration based on size and other laboratory-specific attributes. Furthermore, quality assurance for primary HPV screening, the performance of cytology as a triage test, and that of colposcopic biopsy in vaccinated cohorts are additional challenges that affect laboratory reporting in the primary HPV screening paradigm. The Laboratory Infrastructure Workgroup has been working on developing educational and practical resources to address many of these concerns. As many as 20% of patients in the United States are currently screened for cervical cancer using cytology alone.6 These patients tend to be served by safety-net providers in underserved areas and are more likely to be low-income and from communities of color.7 Screening with cytology alone requires more frequent testing, frequent follow-up for minor, low-risk abnormalities, and does not screen for high-risk HPV, the causative agent of virtually all cases of cervical cancer. Although it is more specific in detecting precancer, cytology is less sensitive than HPV screening, has a high number of equivocal results, and has interlaboratory variability. HPV self-sampling, once US Food and Drug Administration-approved, may be especially helpful to improve screening rates in currently underscreened populations. Therefore, changing screening practices from cytology alone to primary HPV screening is essential and may have a different set of challenges than the transition faced by programs performing cotesting, such as access and cost considerations. The Moving from Cytology Alone Workgroup is addressing the specific needs and barriers anticipated for these lower resource programs. Information technology plays an important role in how health care providers order and manage primary HPV screening tests and how laboratories handle patient specimens and report results. The Information Technology/Electronic Health Records Needs Workgroup is identifying anticipated barriers that health systems may face and outlining recommendations to address them, recognizing that recommendations must be broad enough to apply to different electronic health record (EHR) platforms but specific enough to be useful. The importance of standardized structured data to facilitate implementation of cervical cancer screening and management clinical decision support systems into the EHR will be emphasized and explained. National Current Procedural Terminology codes and Logical Observation Identifiers Names and Codes terminology currently do not differentiate between HPV tests collected for primary HPV screening versus cotesting, which affects accurate test ordering, results tracking, and preventive care tracking tools. This issue is also being addressed by this workgroup. In the United States, payors significantly affect which screening modalities are used in clinical practice. For a successful transition to the widespread use of primary HPV screening, the Insurance Coverage/Payors Workgroup is providing support for billing and coding for primary HPV screening. It is essential that these billing codes be available to use for patients starting at age 25 years. In addition, insurance plans across the country will need to work with their network providers to support the use of primary HPV screening. One challenge faced by this workgroup is the need to balance efforts to promote the use of primary HPV screening while ascertaining that low-resource health centers providing care to the most at-risk patients are not penalized for anticipated delays in uptake of new screening guidelines based on the costs and logistics of capital investments and implementation. Implementation processes of previous cervical cancer screening guidelines have demonstrated that patient perception and education are important considerations when implementing new approaches. This will likely be the case for primary HPV screening and screening done using self-collected specimens in the future. The Patient Perceptions Workgroup is creating educational tools for patients that will destigmatize the role of HPV in cervical cancer screening and encourage use of the right test(s) for the right patient at the right time. Although primary HPV screening has been adopted in many countries, this workgroup will focus on issues facing women and people with a cervix in the United States that are often different than those in other countries because of cultural differences and/or different health care delivery models. The combined efforts of these six workgroups are resulting in the creation of a catalog of resources for providers, professional societies, health systems, patients, payors, and various other stakeholders. There is intentional overlap among the workgroups and the issues that they aim to address. With the support of the Steering Committee, workgroups collaborate on issues and deliverables that are cross-cutting. We will inform partners about our work and outcomes through commentaries like this one as well as through presentations, workshops at professional society meetings, social media and email communications, website announcements, and other stakeholder forums.2, 8 Upon dissemination of the implementation report and tools, the members of this initiative hope to see guideline alignment and primary HPV screening being used more across the United States. This initiative will help to advance future cervical cancer areas of work, including preparing for self-sampling, and other guideline implementation opportunities. The PHSI innovatively accelerates progress beyond guideline development and into the guideline implementation space. This initiative is a crucial step in the successful adoption of primary HPV screening and guideline alignment across organizations. In addition, the initiative is positively contributing to growing synergistic relationships and is a foundation for the newly formed ACS National Roundtable on Cervical Cancer (NRTCC).9 The ACS NRTCC aims accelerate progress toward cervical cancer elimination by reducing barriers to care, eliminating disparities, reducing harms, and promoting new technologies that reduce the morbidity and mortality of cervical cancer for everyone. Achieving the Initiative's objectives and harnessing the power of these collaborative relationships over the next year will provide a critical and model infrastructure to support advancements in cervical cancer prevention and elimination in the coming years through the ACS NRTCC and other channels. To learn more and give comment or input to our efforts, you can visit our website (cervicalroundtable.org). The authors disclosed no conflicts of interest.

University of Minnesota, Minneapolis, MN Correspondence to: Levi Downs, MD, MS, FACOG, 23219 Stringtown Rd, #210, Clarksburg, MD 20871. E-mail: [email protected]

ABSTRACT The American Cancer Society (ACS) released updated cervical cancer screening guidelines in 2020 that endorse a shift in practice to primary human papillomavirus (HPV) screening in people with a cervix, beginning at ages of 25-65 years. When access to US Food and Drug Administration-approved primary HPV testing is not available, the ACS offers cotesting or cytology as acceptable alternative strategies but suggests that these testing modalities may be excluded from future iterations of the guidelines. The ASCCP recognizes the benefits and risks of primary HPV cervical cancer screening while acknowledging the barriers to widespread adoption, including implementation issues, the impact of limited HPV vaccination in the United States, and inclusion of populations who may not be well represented on primary HPV screening trials, such as underrepresented minorities. The ASCCP endorses the 2018 US Preventive Services Task Force Recommendation Statement and supports the ACS cervical cancer screening guidelines. Most importantly, the ASCCP endorses any cervical cancer screening for secondary prevention of cervical cancer and recommends interventions that improve screening for those who are underscreened or unscreened.

•Public health education with media campaigns centered around HPV health risks and vaccine safety •Public health funding allowing widespread access for all adolescents and young adults •Education and incentives for primary healthcare providers to vaccinate •HPV vaccine mandates or school-based vaccination

Background: Black women diagnosed with endometrial cancer (EC) experience worse outcomes compared with white women. Differences in receipt of treatment are postulated to contribute to this disparity. While underuse of surgical treatment among black women is well documented, we know less about racial differences in adjuvant treatment. We therefore examined receipt of adjuvant treatment among black and white women in the NRG Oncology/Gynecology Oncology Group (GOG) 210 Study, a large prospective cohort of women with EC who received uniform surgical treatment but varying adjuvant therapy regimens. Methods: Our analysis included 615 black and 4,283 white women with EC who underwent either an abdominal hysterectomy or laparoscopic-assisted vaginal hysterectomy with bilateral salpingo-oophorectomy and lymph node dissection. At study enrollment, women completed a questionnaire that assessed race as well as risk factors for EC. Tumor characteristics were available from surgical pathology reports and a centralized review by pathologists with expertise in gynecologic cancers. Adjuvant treatment was documented at the time of the postoperative clinical visits and was categorized as none (54.3%), radiotherapy only (16.5%), chemotherapy only (n=15.2%), and radiotherapy and chemotherapy (14.0%). We used polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between race and receipt of adjuvant therapy in the overall study population and stratified by tumor subtype (combination of histology and grade) adjusted for age, income, education, and stage. Results: Black compared with white women had higher odds of receiving combination radiotherapy and chemotherapy compared to no adjuvant therapy (OR=1.35, 95% CI=1.01-1.79) but no difference in receipt of radiotherapy only (OR=0.95, 95% CI=0.72-1.25) or chemotherapy only (OR=0.88 (0.64-1.20) was observed. In tumor-subtype stratified models, black women diagnosed with low-grade endometrioid (OR=2.04, 95% CI=1.06-3.93) or serous tumors (OR=1.81, 95% CI=1.07-3.08) had higher odds of receiving radiotherapy and chemotherapy than white women, but race was not associated with receipt of radiotherapy and chemotherapy for women with high-grade endometrioid, carcinosarcoma, mixed-cell, or clear-cell tumors. Moreover, the tumor-subtype stratified analyses revealed no racial differences in receipt of radiotherapy-only or chemotherapy-only regimens. Conclusions: In this study of women with EC who received uniform surgical treatment, we observed racial differences in receipt of some adjuvant treatment regimens but not others. Among women with indolent (i.e., low-grade endometrioid) or aggressive (i.e., serous) tumors, black women had higher odds of receiving radiotherapy and chemotherapy compared to white women. Radiotherapy and chemotherapy treatment is potentially contraindicated for women with indolent tumors, which suggests a need to understand the reasons why clinicians might overprescribe these therapies for black women. Overall, our results suggest racial differences in receipt of radiotherapy and chemotherapy, but not for other regimens. Citation Format: Ashley Felix, David Cohn, Theodore Brasky, David Mutch, William Creasman, Premal Thaker, Joan Walker, Richard Moore, Shashikant Lele, Saketh Guntupalli, Levi Downs, Christa Nagel, John Boggess, Michael Pearl, Olga Ioffe, Wei Deng, Marcus Randall, Louise Brinton. Receipt of adjuvant endometrial carcinoma treatment according to race: An NRG Oncology/Gynecologic Oncology Group 210 Study [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A85.

Objective The aim of the study was to estimate the excess cost of guideline nonadherent cervical cancer screening in women beyond the recommended screening ages or posthysterectomy in a single healthcare system. Materials and Methods All Pap tests performed between September 1, 2012, and August 31, 2014, in women younger than 21 years, older than 65 years, or after hysterectomy, were coded as guideline adherent or nonadherent per the 2012 America Society of Colposcopy and Clinical Pathology guidelines. We assumed management of abnormal results per the 2013 America Society of Colposcopy and Clinical Pathology management guidelines. Costs were obtained from a literature review and Center for Medicare and Medicaid Services data and applied to nonadherent screening and subsequent diagnostic tests. Results During this period, 1,398 guideline nonadherent Pap tests were performed (257 in women <21 years, 536 in women >65 years, and 605 after hysterectomy), with 88 abnormal results: 35 (13.5%) in women younger than 21 years, 14 (2.6%) in women older than 65 years, and 39 (6.5%) in women after hysterectomy. The excess cost for initial screening, diagnostic tests, and follow-up was US $35,337 for 2 years in women younger than 21 years, US $54,378 for 5 years in women older than 65 years, and US $77,340 for 5 years in women after hysterectomy, resulting in a total excess cost of US $166,100 for 5 years. Of the 1,398 women who underwent guideline nonadherent screening, there were only 2 (0.1%) diagnoses of high-grade dysplasia (VaIN3). Conclusions Guideline nonadherent cervical cancer screening in women beyond the recommended screening ages and posthysterectomy resulted in costs exceeding US $160,000 for screening, diagnostic tests, and follow-up with minimal improvement in detection of high-grade dysplasia.

BACKGROUND: Black women with endometrial cancer are more likely to die of their disease compared with white women with endometrial cancer. These survival disparities persist even when disproportionately worse tumor characteristics among black women are accounted. Receipt of less complete adjuvant treatment among black patients with endometrial cancer could contribute to this disparity. OBJECTIVE: We assessed the hypothesis that black women with endometrial cancer are less likely than their white counterparts to receive adjuvant treatment within subgroups defined by tumor characteristics in the NRG Oncology/Gynecology Oncology Group 210 Study. STUDY DESIGN: Our analysis included 615 black and 4283 white women with endometrial cancer who underwent hysterectomy. Women completed a questionnaire that assessed race and endometrial cancer risk factors. Tumor characteristics were available from pathology reports and central review. We categorized women as low-, intermediate-, or high-risk based on the European Society for Medical Oncology definition. Adjuvant treatment was documented during postoperative visits and was categorized as no adjuvant treatment (54.3%), radiotherapy only (16.5%), chemotherapy only (15.2%), and radiotherapy plus chemotherapy (14.0%). We used polytomous logistic regression to estimate odds ratios and 95% confidence intervals for multivariable-adjusted associations between race and adjuvant treatment in the overall study population and stratified by tumor subtype, stage, or European Society for Medical Oncology risk category. RESULTS: Overall, black women were more likely to have received chemotherapy only (odds ratio, 1.40; 95% confidence interval, 1.04-1.86) or radiotherapy plus chemotherapy (odds ratio, 2.01; 95% confidence interval, 1.54-2.62) compared with white women in multivariable-adjusted models. No racial difference in the receipt of radiotherapy only was observed. In tumor subtype-stratified models, black women had higher odds of receiving radiotherapy plus chemotherapy than white women when diagnosed with low-grade endometrioid (odds ratio, 2.04; 95% confidence interval, 1.06-3.93) or serous tumors (odds ratio, 1.81; 95% confidence interval, 1.07-3.08). Race was not associated with adjuvant treatment among women who had been diagnosed with other tumor subtypes. In stage-stratified models, we observed no racial differences in the receipt of adjuvant treatment. In models that were stratified by European Society for Medical Oncology risk group, black women with high-risk cancer were more likely to receive radiotherapy plus chemotherapy compared with white women (odds ratio, 1.41; 95% confidence interval, 1.03-1.94). CONCLUSION: Contrary to our hypothesis, we observed higher odds of specific adjuvant treatment regimens among black women as compared with white women within specific subgroups of endometrial cancer characteristics.

OBJECTIVE:To estimate whether a rapid recovery program would reduce length of stay among patients undergoing laparotomy on a gynecologic oncology service.METHODS:We conducted a prospective, randomized, controlled trial comparing an enhanced recovery after surgery protocol with routine postoperative care among women undergoing laparotomy on the gynecologic oncology service. Protocol elements included: preoperative counseling, regional anesthesia, intraoperative fluid restriction, and early postoperative ambulation and feeding. A sample size of 50 per group (N=100) was planned to achieve 80% power to detect a two-day difference in our primary outcome, length of hospital stay; secondary outcomes included: total daily narcotics used, time to postoperative milestones, and complications.RESULTS:A total of 112 women were enrolled between 2013 and 2015. Nine patients did not undergo laparotomy and were excluded, leaving 52 and 51 patients in the control and intervention groups, respectively. There was no difference in length of stay between the two groups (median 3.0 in both groups; P=.36). Enhanced recovery after surgery patients used less narcotics on day 0 (10.0 compared with 5.5 morphine equivalents in the control and intervention arms, respectively, P=.09) and day 2 (10.0 compared with 7.5 morphine equivalents, respectively; P=.05); however, there was no statistically significant difference between groups in any of the secondary outcomes. Post hoc analysis based on actual anesthesia received also failed to demonstrate a difference in time to discharge.CONCLUSION:When compared with usual care, introducing a formal enhanced recovery after surgery protocol did not significantly reduce length of stay.CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, https://clinicaltrials.gov, NCT01705288.

Non‐Hispanic black (NHB) women are more likely to experience an endometrial carcinoma (EC) recurrence compared to non‐Hispanic white (NHW) women. The extent to which tumor characteristics, socioeconomic status (SES) and treatment contribute to this observation is not well defined. In the NRG Oncology/Gynecology Oncology Group (GOG) 210 Study we evaluated associations between race/ethnicity and EC recurrence according to tumor characteristics with adjustment for potential confounders. Our analysis included 3,199 NHW, 532 NHB and 232 Hispanic women with EC. Recurrence was documented during follow‐up. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between race/ethnicity and EC recurrence in models stratified by histologic subtype (low‐grade endometrioid, high‐grade endometrioid, serous, mixed cell, carcinosarcoma, clear cell) or stage (I, II, III) and adjusted for age, SES, body mass index, smoking status and treatment. In histologic subtype‐stratified models, higher EC recurrence was noted in NHB women with low‐grade endometrioid (HR = 1.94, 95% CI = 1.21–3.10) or carcinosarcomas (HR = 1.66, 95% CI = 0.99–2.79) compared to NHWs. In stage‐stratified models, higher EC recurrence was noted among NHB women with stage I (HR = 1.48, 95% CI = 1.06–2.05) and Hispanic women with stage III disease (HR = 1.81, 95% CI = 1.11–2.95). Our observations of higher EC recurrence risk among NHB and Hispanic women, as compared to NHW women, were not explained by tumor characteristics, SES, treatment or other confounders. Other factors, such as racial differences in tumor biology or other patient factors, should be explored as contributors to racial disparities in EC recurrence.

BACKGROUND: Black women diagnosed with endometrial carcinoma have a higher risk of recurrence compared with white women. Higher recurrence risk among black women is due, in part, to a greater frequency of aggressive tumor characteristics including non-endometrioid histologies and advanced stage tumors. The risk of recurrence for black and white women within distinct tumor groupings has not been well-examined due to low numbers of black women and under-representation of aggressive histologic subtypes in single institution studies. Therefore, we examined the association between self-reported race and recurrence risk stratified by histologic subtype in the NRG Oncology/Gynecology Oncology Group (GOG) 210, a prospective observational study that enrolled 6,124 newly diagnosed endometrial carcinoma patients between 2003 and 2011. METHODS: We restricted this analysis to 618 black and 4,316 white women with endometrial carcinoma. At study enrollment, women completed a questionnaire that assessed risk factors for gynecologic cancers. Recurrence, defined as evidence of disease following complete response to primary therapy, was abstracted from medical records. Tumor characteristics were available from surgical pathology reports and a centralized review by pathologists with expertise in gynecologic cancers. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between race (black vs. white) and recurrence risk in models stratified by histologic subtype (low-grade endometrioid, high-grade endometrioid, serous, mixed epithelial, carcinosarcoma, clear cell) and adjusted for stage (I, II, III, IV), age at diagnosis (continuous), and adjuvant therapy (none, chemotherapy, radiation, chemotherapy and radiation, unknown). We also examined income ($20,000-$39,999, $40,000-$69,999, ≥$70,000) and education (high school/GED, some college/technical school, college graduate/beyond) as potential mediators of the association between race and endometrial carcinoma recurrence risk using the Baron-Kenny method. Median follow-up time was 5 years. RESULTS: Black women were more frequently diagnosed with non-endometrioid (52.9% vs. 31.8%) and advanced stage (Stage III or IV: 29.0% vs. 21.1%) tumors compared with white women. Recurrence was documented in 26% of black and 17% of white endometrial carcinoma patients. In histologic subtype-stratified models adjusted for stage, age, and adjuvant therapy, a higher risk of recurrence was noted in black women with low-grade endometrioid (HR=1.65, 95% CI=1.07-2.54), mixed epithelial (HR=1.75, 95% CI=1.13-2.71), or carcinosarcomas (HR=1.55, 95% CI=1.03-2.31) compared with white women. No significant race-recurrence relationships were observed among women diagnosed with high-grade endometrioid, serous, or clear cell tumors. After adjustment for income and education, the association of black race and recurrence risk remained elevated, but was not statistically significant: low-grade endometrioid (HR=1.52, 95% CI=0.97-2.38), mixed epithelial (HR=1.56, 95% CI=0.98-2.50), and carcinosarcoma (HR=1.48, 95% CI=0.98-2.25). Further, neither income nor education were significantly associated with recurrence risk in the multivariable models. CONCLUSIONS: Our study provides evidence that racial disparities in endometrial carcinoma recurrence risk vary by histologic subtype. Socioeconomic factors do not explain black-white differences in endometrial carcinoma recurrence risk. Future studies exploring the role of biological factors and post-diagnosis surveillance contributing to racial differences in endometrial carcinoma recurrence are warranted. Citation Format: Ashley S. Felix, Theodore Brasky, David Cohn, Scott McMeekin, David Mutch, Creasman William, Premal Thaker, Joan Walker, Richard Moore, Shashikant Lele, Saketh Guntupalli, Levi Downs, Christa Nagel, John Boggess, Michael Pearl, Olga Ioffe, Kay Park, Shamshad Ali, Louise Brinton. Endometrial carcinoma recurrence in black and white women in the NRG Oncology/Gynecologic Oncology Group 210 trial. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr C44.

Background Recent data suggest that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with reductions in endometrial cancer risk, yet very few have examined whether their use is related to prognosis among endometrial cancer patients. Methods Study subjects comprised 4374 participants of the NRG Oncology/Gynecology Oncology Group 210 Study with endometrial carcinoma who completed a presurgical questionnaire that assessed history of regular prediagnostic NSAID use and endometrial cancer risk factors. Recurrences, vital status, and causes of death were obtained from medical records and cancer registries. Fine-Gray semiproportional hazards regression estimated adjusted subhazard ratios (HRs) and 95% confidence intervals (CIs) for associations of NSAID use with endometrial carcinoma-specific mortality and recurrence. Models were stratified by endometrial carcinoma type (ie, type I [endometrioid] vs type II [serous, clear cell, or carcinosarcoma]) and histology. Results Five hundred fifty endometrial carcinoma-specific deaths and 737 recurrences occurred during a median of five years of follow-up. NSAID use was associated with 66% (HR = 1.66, 95% CI = 1.21 to 2.30) increased endometrial carcinoma-specific mortality among women with type I cancers. Associations were statistically significant for former and current users, and strongest among former users who used NSAIDs for 10 years or longer (HR = 2.23, 95% CI = 1.19 to 4.18, two-sided P trend = .01). NSAID use was not associated with recurrence or endometrial carcinoma-specific mortality among women with type II tumors. Conclusions In this study, use of NSAIDs was associated with increased endometrial carcinoma-specific mortality, especially in patients with type I tumors. Barring a clear biologic mechanism by which NSAIDs would increase the risk of cause-specific mortality, cautious interpretation is warranted.

OBJECTIVE:To estimate the proportion of guideline nonadherent Pap tests in women aged younger than 21 years and older than 65 years and posthysterectomy in a single large health system. Secondary objectives were to describe temporal trends and patient and health care provider characteristics associated with screening in these groups. METHODS:A retrospective cross-sectional chart review was performed at Fairview Health Services and University of Minnesota Physicians. Reasons for testing and patient and health care provider information were collected. Tests were designated as indicated or nonindicated per the 2012 cervical cancer screening guidelines. Point estimates and descriptive statistics were calculated. Patient and health care provider characteristics were compared between indicated and nonindicated groups using χ and Wilcoxon rank-sum tests. RESULTS:A total of 3,920 Pap tests were performed between September 9, 2012, and August 31, 2014. A total of 257 (51%; 95% confidence interval [CI] 46.1-54.9%) of tests in the younger than 21 years group, 536 (40%; 95% CI 37.7-43.1%) in the older than 65 years group, and 605 (29%; 95% CI 27.1-31.0%) in the posthysterectomy group were not indicated. White race in the older than 65 years group was the only patient characteristic associated with receipt of a nonindicated Pap test (P=.007). Health care provider characteristics associated with nonindicated Pap tests varied by screening group. Temporal trends showed a decrease in the proportion of nonindicated tests in the younger than 21 years group but an increase in the posthysterectomy group. CONCLUSION:For women aged younger than 21 years and older than 65 years and posthysterectomy, 35% of Pap tests performed in our health system were not guideline-adherent. There were no patient or health care provider characteristics associated with guideline nonadherent screening across all groups.

Background: Stage is a critical determinant of treatment among endometrial carcinoma patients; understanding patterns of tumor spread may suggest approaches to improve staging. Specifically, the importance of exfoliation of endometrial carcinoma cells through the fallopian tubes into the peritoneum is ill defined. We assessed the hypothesis that tubal ligation (TL), which should impede transtubal passage of cells, is associated with lower endometrial carcinoma stage at presentation and, consequently, lower mortality.Methods: The NRG Oncology/Gynecologic Oncology Group (GOG) 210 Trial included 4489 endometrial carcinoma patients who completed a risk factor questionnaire that included TL history. Pathology data were derived from clinical reports and central review. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between TL with stage and peritoneal metastasis, overall and by tumor subtype. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals for TL and mortality. All statistical tests were two-sided.Results: Compared with stage I, TL was inversely associated with stage III (OR = 0.63, 95% CI = 0.52 to 0.78) and stage IV carcinomas (OR = 0.14, 95% CI = 0.08 to 0.24) overall and among individual tumor subtypes. TL was inversely related to peritoneal metastasis overall (OR = 0.39, 95% CI = 0.22 to 0.68) and among serous carcinomas (OR = 0.28, 95% CI = 0.11 to 0.68). In multivariable models unadjusted for stage, TL was associated with lower endometrial carcinoma-specific mortality (HR = 0.74, 95% CI = 0.61 to 0.91); however, adjustment for stage eliminated the survival advantage. Similar relationships with all-cause mortality were observed.Conclusions: TL is associated with lower stage and mortality among women with aggressive endometrial carcinomas, suggesting transtubal spread is clinically important. Future studies should evaluate whether detection of intraluminal tumor cells is prognostically relevant.

Background. Few studies have analyzed relationships between risk factors for endometrial cancer, especially with regard to aggressive (non-endometrioid) histologic subtypes, and prognosis. We examined these relationships in the prospective NRG Oncology/Gynecologic Oncology Group 210 trial.Methods. Prior to surgery, participants completed a questionnaire assessing risk factors for gynecologic cancers. Pathology data were derived from clinical reports and central review. We used the Fine and Gray subdistribution hazards model to estimate subhazard ratios (HRs) and 95% confidence intervals (Cls) for associations between etiologic factors and cause-specific subhazards in the presence of competing risks. These models were stratified by tumor subtype and adjusted for stage and socioeconomic status indicators.Results. Median follow-up was 60 months after enrollment (range: 1 day-118 months). Among 4609 participants, a total of 854 deaths occurred, of which, 582 deaths were attributed to endometrial carcinoma. Among low-grade endometrioid cases, endometrial carcinoma-specific subhazards were significantly associated with age at diagnosis (HR = 1.04, 95% CI = 1.01-1.06 per year, P-trend) and BMI (class II obesity vs. normal BMI: HR = 2.29, 95% CI = 1.06-4.98, P-trend = 0.01). Among high-grade endometrioid cases, endometrial carcinoma-specific subhazards were associated with age at diagnosis (HR = 1.05, 95% CI = 1.02-1.07 per year, P-trend < 0.001). Among non-endometrioid cases, endometrial carcinoma-specific subhazards were associated with parity relative to nulliparity among serous (HR = 0.55, 95% Cl = 0.36-0.82) and carcinosarcoma cases (HR = 2.01,95% Cl = 1.00-4.05).Discussion. Several endometrial carcinoma risk factors are associated with prognosis, which occurs in a tumor-subtype specific context. If confirmed, these results would suggest that factors beyond histopathologic features and stage are related to prognosis. ClinicalTrials.gov Identifier: NCT00340808. Published by Elsevier Inc.

OBJECTIVE: The goal of this pilot study was to evaluate adherence to the 2012 cervical cancer screening guidelines among health care providers in a large health maintenance organization.STUDY DESIGN: A cross-sectional survey evaluating knowledge, reported practices, and views of the 2012 cervical cancer screening guidelines was distributed to 325 health care providers within HealthPartners. The survey was divided into 3 sections: (1) provider demographics; (2) knowledge of the 2012 age-specific cancer screening guidelines; and (3) provider practice. Comparisons based on appropriate knowledge and practice of the guidelines were made using Fisher exact tests.RESULTS: The response rate was 42%. Of 124 respondents, 15 (12.1%) reported they were not aware of the 2012 guideline changes. Only 7 (5.7%) respondents answered all the knowledge questions correctly. A majority of respondents reported correct screening practices in the 21-29 year patient age group (65.8%) and in the >65 year patient age group (74.3%). Correct screening intervals in the 30-65 year patient age group varied by modality, with 89.3% correctly screening every 3 years with Pap smear alone, but only 57.4% correctly screening every 5 years with Pap smear + human papillomavirus cotesting. The most frequently cited reasons for not adhering were lack of knowledge of the guidelines and patient demand for a different screening interval.CONCLUSION: Adherence to the 2012 cervical cancer screening guidelines is poor due, in part, to a lack of knowledge of the guidelines. Efforts should focus on improved provider and patient education, and methods that facilitate adherence to the guidelines such as electronic health record order sets.

Purpose: Cancer survivors are at an increased risk for fractures, but lack of effective and economical biomarkers limits quantitative assessments of marrow fat (MF), bone mineral density (BMD) and their relation in response to cytotoxic cancer treatment. We report dual energy CT (DECT) imaging, commonly used for cancer diagnosis, treatment and surveillance, as a novel biomarker of MF and BMD.Methods: We validated DECT in pre-clinical and phase I clinical trials and verified with water-fat MRI (WF-MRI), quantitative CT (QCT) and dual-energy X-ray absorptiometry (DXA). Basis material composition framework was validated using water and small-chain alcohols simulating different components of bone marrow. Histologic validation was achieved by measuring percent adipocyte in the cadaver vertebrae and compared with DECT and WF-MRI. For a phase I trial, sixteen patients with gynecologic malignancies (treated with oophorectomy, radiotherapy or chemotherapy) underwent DECT, QCT, WF-MRI and DXA before and 12 months after treatment. BMD and MF percent and distribution were quantified in the lumbar vertebrae and the right femoral neck.Results: Measured precision (3 mg/cm(3)) was sufficient to distinguish test solutions. Adiposity in cadaver bone histology was highly correlated with MF measured using DECT and WF-MRI (r = 0.80 and 0.77, respectively). In the clinical trial, DECT showed high overall correlation (r = 0.77, 95% CI: 0.69, 0.83) with WF-MRI. MF increased significantly after treatment (p < 0.002). Chemotherapy and radiation caused greater increases in MF than oophorectomy (p < 0.032). L4 BMD decreased 14% by DECT, 20% by QCT, but only 5% by DXA (p < 0.002 for all). At baseline, we observed a statistically significant inverse association between MF and BMD which was dramatically attenuated after treatment.Conclusion: Our study demonstrated that DECT, similar to WF-MRI, can accurately measure marrow adiposity. Both imaging modalities show rapid increase in MF following cancer treatment. Our results suggest that MF and BMD cannot be used interchangeably to monitor skeletal health following cancer therapy. (C) 2014 Elsevier Inc. All rights reserved.