SummaryBackgroundEndometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes of ovarian cancer.MethodsData from 13 ovarian cancer case–control studies, which were part of the Ovarian Cancer Association Consortium, were pooled and logistic regression analyses were undertaken to assess the association between self-reported endometriosis and risk of ovarian cancer. Analyses of invasive cases were done with respect to histological subtypes, grade, and stage, and analyses of borderline tumours by histological subtype. Age, ethnic origin, study site, parity, and duration of oral contraceptive use were included in all analytical models.Findings13 226 controls and 7911 women with invasive ovarian cancer were included in this analysis. 818 and 738, respectively, reported a history of endometriosis. 1907 women with borderline ovarian cancer were also included in the analysis, and 168 of these reported a history of endometriosis. Self-reported endometriosis was associated with a significantly increased risk of clear-cell (136 [20·2%] of 674 cases vs 818 [6·2%] of 13 226 controls, odds ratio 3·05, 95% CI 2·43–3·84, p<0·0001), low-grade serous (31 [9·2%] of 336 cases, 2·11, 1·39–3·20, p<0·0001), and endometrioid invasive ovarian cancers (169 [13·9%] of 1220 cases, 2·04, 1·67–2·48, p<0·0001). No association was noted between endometriosis and risk of mucinous (31 [6·0%] of 516 cases, 1·02, 0·69–1·50, p=0·93) or high-grade serous invasive ovarian cancer (261 [7·1%] of 3659 cases, 1·13, 0·97–1·32, p=0·13), or borderline tumours of either subtype (serous 103 [9·0%] of 1140 cases, 1·20, 0·95–1·52, p=0·12, and mucinous 65 [8·5%] of 767 cases, 1·12, 0·84–1·48, p=0·45).InterpretationClinicians should be aware of the increased risk of specific subtypes of ovarian cancer in women with endometriosis. Future efforts should focus on understanding the mechanisms that might lead to malignant transformation of endometriosis so as to help identify subsets of women at increased risk of ovarian cancer.FundingOvarian Cancer Research Fund, National Institutes of Health, California Cancer Research Program, California Department of Health Services, Lon V Smith Foundation, European Community's Seventh Framework Programme, German Federal Ministry of Education and Research of Germany, Programme of Clinical Biomedical Research, German Cancer Research Centre, Eve Appeal, Oak Foundation, UK National Institute of Health Research, National Health and Medical Research Council of Australia, US Army Medical Research and Materiel Command, Cancer Council Tasmania, Cancer Foundation of Western Australia, Mermaid 1, Danish Cancer Society, and Roswell Park Alliance Foundation.

Background: Hepatitis C virus (HCV) is highly prevalent among homeless persons, yet barriers continue to impede HCV testing and treatment in this population. We studied the experiences of homeless individuals related to accessing HCV care to inform the design of a shelter-based HCV prevention and treatment program. Methods: Homeless shelter clients (10 women and 10 men) of a large shelter in San Francisco participated in gender segregated focus groups. Focus groups followed a semi-structured interview format, which assessed individual, program/system, and societal-level barriers and facilitators to universal HCV testing and linkage to HCV care. Focus group interviews were transcribed, coded, and analyzed using thematic analysis. Results: We identified key barriers to HCV testing and treatment at the individual level (limited knowledge and misconceptions about HCV infection, mistrust of health care providers, co-morbid conditions of substance use, psychiatric and chronic medical conditions), system level (limited advocacy for HCV services by shelter staff), and social level (stigma of homelessness). Individual, system, and social facilitators to HCV care described by participants included internal motivation, financial incentives, prior experiences with rapid HCV testing, and availability of affordable direct acting antiviral (DAA) treatment, respectively. Conclusions: Interrelated individual-and social-level factors were the predominant barriers affecting homeless persons' decisions to engage in HCV prevention and treatment. Integrated models of care for homeless persons at risk for or living with HCV address many of these factors, and should include interventions to improve patient knowledge of HCV and the availability of effective treatments.

Compared with the general population, homeless individuals are at higher risk of hepatitis C infection (HCV) and may face unique barriers in receipt of HCV care. This study sought the perspectives of key stakeholders toward establishing a universal HCV screening, testing, and treatment protocol for individuals accessing homeless shelters. Four focus groups were conducted with homeless shelter staff, practice providers, and social service outreach workers (n = 27) in San Francisco, California, and Minneapolis, Minnesota. Focus groups evaluated key societal, system, and individuallevel facilitators and barriers to HCV testing and management. Interviews were transcribed and analyzed thematically. The societal-level barriers identified were lack of insurance, high-out-of-pocket expenses, restriction of access to HCV treatment due to active drug and/or alcohol use, and excessive paperwork required for HCV treatment authorization from payers. System-level barriers included workforce constraints and limited health care infrastructure, HCV stigma, low knowledge of HCV treatment, and existing shelter policies. At the individual level, client barriers included competing priorities, behavioral health concerns, and health attitudes. Facilitators at the system level for HCV care service integration in the shelter setting included high acceptability and buy in, and linkage with social service providers. Conclusion: Despite societal, system, and individual-level barriers identified with respect to the scale-up of HCV services in homeless shelters, there was broad support from key stakeholders for increasing capacity for the provision of HCV services in shelter settings. Recommendations for the scale-up of HCV services in homeless shelter settings are discussed. (Hepatology Communications 2020;4:646-656).H epatitis C virus (HCV) prevalence is underestimated in underserved populations, including people experiencing homelessness who are at increased risk of HCV infection. (1) According to a recent systematic review of infectious disease prevalence studies, the prevalence of HCV among homeless adults ranges from 9.8% to 52.5%. (2) Among people experiencing homelessness, substance use and mental health disorders are common, and are risk factors for HCV infection. (3,4) Moreover, homelessness has consistently been associated with injection drug use, (5) and engaging in unsafe injection drug-use practices likely drives the high rates of HCV infection documented among this population.

The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at Pp0.10 in a log-additive model: rs2740574 in CYP3A4 (P ¼ 0.011), rs1805386 in LIG4 (P ¼ 0.007), and rs3218536 in XRCC2 (P ¼ 0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: OR homozygous(hom) ¼ 2.50 (95% CI 0.54-11.57, P ¼ 0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20 -6.56, P ¼ 0.017, p het across studies ¼ 0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted.