Racial disparities in endometrial cancer: Where are we after 26 years?

INTRODUCTION: Endometrial cancer is the most commonly diagnosed female genital tract malignancy in the United States of America. Racial disparities surrounding this particular disease have been extensively investigated for over 26-years. We sought to determine if research in this area has led to any significant improvements in this disparity. METHODS: We performed a rapid systematic review of English language publications on racial disparities in endometrial cancer among African American (AAW) and white American women (WAW), from 1997 to 2023. We looked at trends in incidence and survival; impact of known poor prognostic factors (stage at diagnosis, histological subtypes, grade); co-morbidities; differences in treatment (surgery, radiation and chemotherapy); socioeconomic factors; differences in biological and genetic markers; and policies/declarations. RESULTS: During the period under review (1997-2023), there was a notable increase in both disease incidence (39%) and mortality (26%) rates for AAW, in comparison to WAW among whom the incidence rates increased by 2% and mortality rates rose, but 9% less than for AAW. It should be noted that the current incidence rate of 29.4% in AAW represent a reversal of what is was 26-years ago, when the incidence rate was 17.8%. In comparison to WAW, AAW had a higher prevalence of poor prognostic variables, more co-morbidities, lower income levels, less insurance coverage, and were more frequently under treated with surgery, chemotherapy and radiation. To date no actionable molecular/genetic markers have been identified. We were unable to locate any published recommendations or active programs of implementation strategies/policies designed to effectively mitigate the documented racial disparity. CONCLUSION: Racial disparities in disease incidence and mortality in endometrial cancer rates between WAW and AAW have widened during a 26-year period of robust research, suggesting that current research alone is not enough to eliminate this disparity. Based on this rapid systematic review we have identified and analyzed the impact of causation variables on this disparity. Additionally, we have made strong and pertinent recommendations for the benefit of mitigating this escalating racial disparity.

Association of RAD51C germline mutations with breast cancer among Bahamians.

PURPOSE: RAD51C is known as an ovarian cancer gene; however, its role in breast cancer susceptibility is less clear. As part of a larger study, we assessed the role of germline RAD51C mutations in breast cancer development. METHODS: We studied 387 unselected, BRCA1- and BRCA2-negative, Bahamian breast cancer cases and 653 controls to search for novel genetic associations with breast cancer development. During the first phase of the study, whole exome sequencing was utilized in 96 cases to identify an association between novel genes and breast cancer susceptibility. In the second phase of the study, targeted gene sequencing was utilized in the entirety of the cases and controls to identify an association between novel genetic mutations and breast cancer development. RESULTS: A RAD51C mutation was found in five breast cancer cases and in no control (5/387 versus 0/653; p = 0.007). None of the mutation-positive cases reported a family history of ovarian cancer. CONCLUSIONS: These data support increasing evidence that RAD51C mutations contribute to breast cancer susceptibility, although the impact may vary substantially from country to country.

Experience with curative radiotherapy for cervix cancer in the Bahamas for 2006-2016.

BACKGROUND: Cervix cancer is a significant health problem. As access to quality care in Small Island Developing States improves, and cancer centers become established, providers of care can summarize local experience to benchmark system quality and look for ways to further improve value. METHODS: This is a retrospective study of all cases of cervix cancer managed 2006-2016 at The Cancer Centre Bahamas, in conjunction with Princess Margaret Hospital, Nassau, affiliated with The University of West Indies. Seventy-two women received curative radiotherapy or chemoradiotherapy. Herein are reported presenting characteristics, treatments, waiting and overall treatment times, plus outcomes of recurrence, survival, and adverse events. RESULTS: For 68 newly diagnosed cases, median waiting time (diagnosis to commencing treatment) was 110 days. It was 90 days for those 47 cases who had no prior surgery or neoadjuvant chemotherapy. Overall, 99% of intended external radiotherapy fractions, 74% of brachytherapy sessions, and 79% of concurrent weekly chemotherapy were administered. For all 72 cases, median overall treatment time was 63 days; and for the 47 case sub-group, it was 78 days during 2006-2010 and 65 days during 2011-2016 (p = 0.005), so improving over calendar time. Four cases experienced grade 3-4 toxicities. Twelve had urological complications from disease or treatment. Five cases experienced local failure; eight experienced distant failure. Newly diagnosed stage 2B (26/72) had a 2-year survival of 71%. CONCLUSION: This report demonstrates the impact of providing curative radiation-based treatments for cervical cancer in a small state. It suggests ways to further improve operations and justifies additional research.

Multicenter study of human papillomavirus and the human papillomavirus vaccine: knowledge and attitudes among people of African descent.

OBJECTIVE: To compare knowledge and attitudes of human papillomavirus (HPV) and the vaccine between different cultures of African descent. METHODS: A cross-sectional survey of 555 African-Americans and Afro-Caribbeans residing in the US and the Bahamas (BHM) was conducted. RESULTS: General knowledge about HPV and the HPV vaccine differed between the two countries significantly. Bahamian respondents were less likely to have higher numbers of correct knowledge answers when compared to Americans (Adjusted Odds Ratio [Adj. OR] 0.47, 95% Confidence Interval [CI] 0.30-0.75). Older age, regardless of location, was also associated with answering fewer questions correctly (Adj. OR 0.61, 95% CI 0.40-0.92). Attitudes related to HPV vaccination were similar between the US and BHM, but nearly 80% of BHM respondents felt that children should not be able to receive the vaccine without parental consent compared to 57% of American respondents. CONCLUSIONS: Grave lack of knowledge, safety and cost concerns, and influence of parental restrictions may negatively impact vaccine uptake among African-American and Afro-Caribbean persons. Interventions to increase the vaccine uptake in the Caribbean must include medical provider and parental involvement. Effective strategies for education and increasing vaccine uptake in BHM are crucial for decreasing cervical cancer burden in the Caribbean.

The evolution of a novel approach to building surgical capacity for cervical cancer in Africa.

The human, financial, and infrastructural resources required to effectively treat invasive cancer of the cervix are grossly inadequate in the African region, inclusive of a paucity of surgeons capable of performing life-saving radical pelvic surgery for early-stage disease, and the requisite medical ecosystem (blood banking, anesthesia, laboratory, imaging, diagnostics, etc.) Death without treatment, therefore, is a common sequela of cervical cancer in Africa. As African American gynaecologic oncology sub-specialists working in Africa and its Diaspora, we set out to find a way to alter these circumstances. Herein, we provide an overview of our efforts and how they evolved into a novel method of training that rapidly builds surgical capacity for the treatment of early-stage cervical cancer in resource-constrained environments.

Human Papilloma Virus Distribution Across the African Diaspora.

PURPOSE: Understanding the distribution of human papilloma virus (HPV) subtypes in limited-resource settings is imperative for cancer prevention strategies in these regions. The objective of our study is to compare the prevalence of cervical HPV genotypes in women across the African diaspora. METHODS: This study was approved by the African Caribbean Consortium (AC3). Six member institutions (Benin, Ethiopia, The Bahamas, Tobago, Curacao, and Jamaica) provided independently collected HPV data. Prevalence comparisons across for each nation were performed followed by an assessment of anticipated 9-valent vaccine coverage. Chi-square or Fisher's exact tests were used with significance at P < .05. RESULTS: One thousand three hundred fifty high-risk (HR) and 584 low-risk (LR) HPV subtypes were identified in the entire cohort. The most common HR HPV subtype was HPV 16 (17.9%) of infections. The distribution of HR and LR subtypes varied by country. The proportion of HR-HPV subtypes covered by the current 9-valent vaccine was lower in African countries compared with the Caribbean countries (47.9% v 67.9%; P < .01). No significant difference was seen for LR subtypes (8.1% African continent v 5.2% Caribbean; P = .20). Marked variation in the proportion of infections covered by the 9-valent vaccine persisted in individual countries. CONCLUSION: Significant variations in HPV prevalence were identified among African and Afro-Caribbean women. A large number of women in these regions are potentially uncovered by current vaccination formulation, particularly low-risk HPV infections.

Gene Sequencing for Pathogenic Variants Among Adults With Breast and Ovarian Cancer in the Caribbean.

Importance: Rates of breast and ovarian cancer are high in the Caribbean; however, to date, few published data quantify the prevalence of inherited cancer in the Caribbean population. Objective: To determine whether deleterious variants in genes that characterize the hereditary breast and ovarian cancer syndrome are associated with the development of breast and ovarian cancer in the English- and Creole-speaking Caribbean populations. Design, Setting, and Participants: This multisite genetic association study used data from germline genetic test results between June 2010 and June 2018 in the Bahamas, Cayman Islands, Barbados, Dominica, Jamaica, Haiti, and Trinidad and Tobago. Next-generation sequencing on a panel of 30 genes and multiplex ligation-dependent probe amplification (BRCA1 and BRCA2) were performed. Medical records were reviewed at time of study enrollment. Women and men diagnosed with breast and ovarian cancer with at least 1 grandparent born in the participating study sites were included; 1018 individuals were eligible and consented to participate in this study. Data were analyzed from November 4, 2019, to May 6, 2020. Exposures: Breast and/or ovarian cancer diagnosis. Main Outcomes and Measures: Rate of inherited breast and ovarian cancer syndrome and spectrum and types of variants. Results: Of 1018 participants, 999 (98.1%) had breast cancer (mean [SD] age, 46.6 [10.8] years) and 21 (2.1%) had ovarian cancer (mean [SD] age, 47.6 [13.5] years). Three individuals declined to have their results reported. A total of 144 of 1015 (14.2%) had a pathogenic or likely pathogenic (P/LP) variant in a hereditary breast and ovarian cancer syndrome gene. A total of 64% of variant carriers had P/LP variant in BRCA1, 23% in BRCA2, 9% in PALB2 and 4% in RAD51C, CHEK2, ATM, STK11 and NBN. The mean (SD) age of variant carriers was 40.7 (9.2) compared with 47.5 (10.7) years in noncarriers. Individuals in the Bahamas had the highest proportion of hereditary breast and ovarian cancer (23%), followed by Barbados (17.9%), Trinidad (12%), Dominica (8.8%), Haiti (6.7%), Cayman Islands (6.3%), and Jamaica (4.9%). In Caribbean-born women and men with breast cancer, having a first- or second-degree family member with breast cancer was associated with having any BRCA1 or BRCA2 germline variant (odds ratio, 1.58; 95% CI, 1.24-2.01; P < .001). A BRCA1 vs BRCA2 variant was more strongly associated with triple negative breast cancer (odds ratio, 6.33; 95% CI, 2.05-19.54; P = .001). Conclusions and Relevance: In this study, among Caribbean-born individuals with breast and ovarian cancer, 1 in 7 had hereditary breast and ovarian cancer. The proportion of hereditary breast and ovarian cancer varied by island and ranged from 23% in the Bahamas to 4.9% in Jamaica. Each island had a distinctive set of variants.

Race and Ethnicity Influence Survival Outcomes in Women of Caribbean Nativity With Epithelial Ovarian Cancer.

Background: Caribbean immigrants represent one of the largest groups of minorities in the United States (US), yet are understudied. Racial and ethnic disparities among women with ovarian cancer have been reported, but not in immigrant populations. Our objective was to evaluate differences in the clinicopathologic features and survival outcomes of Caribbean-born (CB) immigrants with ovarian cancer, with special focus on the influence of race and ethnicity on these measures. Methods: A review of the institutional cancer registry was performed to identify women with known nativity treated for epithelial ovarian cancer between 2005 and 2017. Sociodemographic, clinical, and outcomes data were collected. Analyses were done using chi-square, Cox proportional hazards models, and the Kaplan-Meier method, with significance set at p < 0.05. Results: 529 women were included in the analysis, 248 CB and 281 US-born (USB). CB women were more likely to have residual disease after debulking surgery (31.2 vs. 16.8%, p = 0.009) and be treated at a public facility (62.5 vs. 33.5%, p < 0.001). Black CB women less frequently received chemotherapy compared to White CB women (55.2 vs. 82.2%, p = 0.001). Among all CB women, Hispanic ethnicity was independently associated with improved survival when adjusting for other factors (HR 0.61 [95% CI 0.39-0.95], p = 0.03). White Hispanic CB women had a median overall survival (OS) of 59 months while Black, non-Hispanic CB women had a median OS of 24 months (log-rank p = 0.04). Conclusion: Among Caribbean-born women with ovarian cancer, Hispanic ethnicity is significantly associated with improved survival outcomes, regardless of race.

Short report: Follow-up of Bahamian women with a BRCA1 or BRCA2 mutation.

PURPOSE: We sought to determine to what extent the knowledge of carrying a BRCA1 or BRCA2 mutation influences the uptake of preventive surgeries in Bahamian women, including bilateral salpingo-oophorectomy and bilateral mastectomy. PATIENTS AND METHODS: The study population consisted of 78 female residents of the Bahamas for whom a BRCA1 or BRCA2 mutation had been detected between 2004 and 2014. The mean age of the 78 participants at the time of genetic testing was 46 years (age range 22-73 years). The mean time of follow-up was 4.4 years. RESULTS: Of the 78 study participants, 19 women had a bilateral salpingo-oophorectomy (24%). Seven out of 37 patients who had unilateral breast cancer chose to remove the unaffected contralateral breast (19%). Three of 13 patients with no history of breast cancer chose to have a prophylactic bilateral mastectomy (23%). CONCLUSION: Preventive surgery is an acceptable option for a significant proportion of Bahamian women with a BRCA1 or BRCA2 mutation. It will be important to identify and reduce barriers to preventive surgery in the Bahamas in order that the benefit of getting testing can be fully realized.

High-risk cervical human papillomavirus infections among human immunodeficiency virus-positive women in the Bahamas.

BACKGROUND: High-risk (HR) HPV genotypes other than 16 and 18 have been detected in a significant proportion of immunocompromised females. We aim to evaluate the frequency of HR HPV genotypes in a population of HIV-positive Caribbean women. METHODS: One hundred sixty-seven consecutive, non-pregnant, HIV-positive females ≥18 years were recruited in this study. Each participant received a vaginal examination, PAP smear, and completed a questionnaire. DNA was extracted for HPV testing in 86 patients. RESULTS: Mean age was 39.1 years for women positive for HR HPV and 43.1 years for women negative for HR HPV (P value  = 0.040). 78% (130/167) of the women had HR HPV infections; the prevalence of abnormal cervical cytology was 38% among women who were HR HPV-positive compared to women who were HR HPV-negative (22%). Fifty-one percent of the 86 women with available genotype carried infections with HPV 16 and/or HPV 18; genotypes of unknown risk were also frequently observed. Women who had a CD4+ count of ≤200 had 7 times increased odds of carrying HR HPV infection in comparison to women with CD4+>200. CONCLUSIONS: HR HPV infections in HIV infected females may consist of more than just HPV 16 and 18, but also HPV 52 and 58. Further studies are needed to determine whether HPV 52 and 58 play a significant role in the development of cervical cytological abnormalities in HIV+ women.

The prevalence of cervical cytology abnormalities and human papillomavirus in women infected with the human immunodeficiency virus.

INTRODUCTION: The human papillomavirus (HPV) is the major etiologic agent in the development of cervical cancer and its natural history of infection is altered in persons infected with the human immunodeficiency virus (HIV). The prevalence of HPV infection and cervical dysplasia in the HIV sero-positive females in the Bahamas is not known. Finding out the prevalence would allow for the establishment of protocols to optimize total care of this population and help prevent morbidity and mortality related to cervical cancer. OBJECTIVE: The Objective of this study is to determine the prevalence of high risk HPV genotypes and the prevalence of cervical dysplasia in the HIV sero-positive females attending the Infectious Disease Clinic at the Princess Margaret Hospital, Nassau, Bahamas. METHODS: One hundred consecutive, consenting, non-pregnant, HIV-sero-positive females from the Infectious Disease Clinic at the Princess Margaret Hospital in Nassau, Bahamas were screened for high-risk HPV infections and cervical cytology abnormalities using liquid-based pap smear and signal amplification nucleic acid method for HPV detection. A questionnaire was also utilized to gather demographic information and obtain information on known risk factors associated with HPV infections such numbers of partners. RESULTS: The prevalence of high-risk HPV was 67% and cervical abnormalities were noted in 44% of the study population. High-risk HPV types were more likely to be present in women with CD4+ cell counts less than 400 microl-1 and in women with cervical cytology abnormalities (97%). The most common cervical abnormality was low-grade squamous intraepithelial lesions. CONCLUSION: Findings suggest that HIV-sero positive females should have HPV testing done as part of their normal gynecology evaluation and these patients should be encouraged and provisions be made for ease of access having regular PAP smears and HPV testing.