bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 39: Human Papillomavirus (HPV) DNA Testing Based Cervical Cancer Screening and Triage with CINtec PLUS Cytology Test in HPV Positive Women in Bogalay Township, Ayeyarwady Region, Myanmar
Authors: Shwe Mu Mu , Thwe Khin Kay , Hlaing Su Su , Aye Lynn Pa Pa , Aung Kham Mo , Lwin Nu , Tun Win Maw , Htun Zaw Than
Published: July 2021

Purpose: This study aimed to conduct Human Papillomavirus (HPV) DNA testing based cervical cancer screening among married women in Bogalay Township, Ayeyarwady Region, Myanmar and to triage with CINtec PLUS Cytology test among women who have HPV infection.

Methods: It was a prospective cross-sectional descriptive study. Total of asymptomatic 677 married women (median age-40-years;range 30-55) residing in Bogalay Township, Ayeyarwady Region, Myanmar were screened in 2020. HPV-DNA testing was performed using cobas HPV-DNA-test which detects 14-high-risk-HPV genotypes -16,-18,-31,-33,-35,-39,-45,-51,-52,-56,-58,-59,-66 and-68. Positive HPV cases were followed by liquid-based- cytology (LBC) and CINtec PLUS Cytology i.e, dual-immuno-biomarker technology to simultaneously detect p-16 and Ki-67 to provide a strong indicator of the presence of transforming HPV infections.

Results: HPV was identified in 4.6% (31/677) of screened women in Bogalay Township, Ayeyarwady Region, Myanmar. Among HPV-positive-cases, HPV-16 was 22.6 % (7/31), HPV-18 was 6.5% (2/31) and other-HR-HPV-genotypes (HPV-31,-33,-35,-39,-51,-52,-56,-58,-59,-66and-68) were 70.9% (22/31). In cytological-diagnosis of HPV positive women, 87.1% had cervical cytological abnormalities comprising; 16.1% had high grade squamous intraepithelial lesion (HSIL), 48.4% had low grade squamous intraepithelial lesion (LSIL) and 22.6% had atypical squamous cells of undetermined significance (ASCUS). Only 12.9% were negative for intraepithelial lesion or malignancy (NILM). In CINtec-PLUS-Cytology, all HSIL (100%) cases, 66.7% of LSIL, 14.3% of ASCUS were positive with both p-16 and Ki-67 dual-immuno-biomarker but negative in NILM cases.

Conclusion: This study highlighted that using HPV-DNA test in cervical cancer screening, the highest risk women can be determined. In triage with CINtec-PLUS-Cytology in HPV positive women, women who were more significantly at risk for cervical pre-cancer and cancer as well as women that require referral to colposcopy were identified. In LSIL and ASCUS cases, CINtec-PLUS-Cytology may reduce the number of women that require referral to colposcopy. This study pointed out CINtec-PLUS-Cytology was very useful to confirm the high-grade cervical lesions.

Citation Format: Mu Mu Shwe, Khin Kay Thwe, Su Su Hlaing, Lynn Pa Pa Aye, Kham Mo Aung, Nu Lwin, Win Maw Tun, Zaw Than Htun. Human Papillomavirus (HPV) DNA Testing Based Cervical Cancer Screening and Triage with CINtec PLUS Cytology Test in HPV Positive Women in Bogalay Township, Ayeyarwady Region, Myanmar [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 39.
Abstract 4: Impact of Immunohistochemistry on Diagnostic Accuracy for Pediatric Cancer in Tanzania
Authors: Bhuko Jeffer , Minja Caroline , McDermott Michael , Osullivan Maureen , Scanlan Trish , Schroeder Kristin
Published: July 2021

Purpose: The current study evaluates the impact of immunohistochemistry (IHC) on diagnostic accuracy for pediatric cancer in Tanzania, and identifies the most common biomarkers used for diagnostic differentiation in our setting.

Methods: Pathology samples for children diagnosed with cancer at Bugando Medical Centre (Mwanza, Tanzania) in 2018 were evaluated using H&E staining. Basic demographic information from histology form was recorded, including patient age, sex, and sample collection, as well as the reported histopathology results from BMC. Additional tissue from histology block was sent to Muhimbili National Hospital for IHC review. The histopathology results were compared for diagnostic agreement, change in diagnosis, and identified which biomarkers were necessary for diagnostic confirmation.

Results: One hundred and five (105) pediatric cancer patients were reviewed. 58 (55.2%) were female median age of 6 years (IQR 3-9 years). Most common pediatric diagnoses were Burkitt lymphoma and Non Hodgkin Lymphoma specifically Diffuse Large B-cell lymphoma, anaplastic large cell lymphoma, FL, LL. Overall histology concordance between H&E and IHC was 51.0%. Most common discordant diagnosis was NHL of ALCL (ALK1-negative, CD-45, 30-positivity). Most concordant was Leukemia (BCR-ABL). Diagnostic specificity (example: in Non-Hodgkin Lymphoma) improved for 17.6% (n=18). The most common diagnosis with increased specificity was DLBCL. Among NHL, 39% (n=7) were ALCL, 27% (n=5) DLBCL, 17% (n=3) Lymphoblastic Lymphoma, 17% (n=3) Follicular lymphoma. The use of immunohistochemistry resulted in a change in diagnosis for 31.4% (n=32) of patient. The most common changed diagnosis was Burkitt Lymphoma and Sarcoma.

Conclusion: Immunohistochemistry is critically important for accurate diagnosis of pediatric cancer, with over 30% of all cases identified as having treatment changing diagnoses. IHC training is critical and a limited common biomarker panel can successfully be used in low resource countries to improve treatment selection.

Citation Format: Jeffer Bhuko, Caroline Minja, Michael McDermott, Maureen Osullivan, Trish Scanlan, Kristin Schroeder. Impact of Immunohistochemistry on Diagnostic Accuracy for Pediatric Cancer in Tanzania [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 4.
Abstract 54: A Comprehensive Survey to Identify Barriers to and Facilitators of Cervical Cancer Screening in Women With HIV in Guangxi, China
Authors: Zhao Ran , Liang Shujia , Teoh Deanna , Fei Yunqing , Pang Xianwu , Kulasingam Shalini
Published: July 2021

Purpose: To assess perceived barriers to and facilitators of cervical cancer screening in women with HIV in Guangxi, China.

Methods: Using a cross-sectional design, we administered a survey among women with HIV aged 21-65 years from August to October 2019 in Guangxi, China. A 100-item survey was developed in English and translated into Chinese. Age criterion was concordant with the cervical cancer screening recommendations. We assessed knowledge, attitudes, and beliefs about cervical cancer and cervical cancer screening, identified potential barriers to and facilitators of cervical cancer screening programs for women with HIV, and assessed potential risk factors for cervical cancer. We conducted descriptive data analyses with the collected responses.

Results: A total of 101 participants, on average 39.5 years old (IQR: 34.5-44 years old), completed the survey. The mean CD4 cell count was 705 cell/µl (IQR: 493-854 cell/µl). 47% of the women had been screened for cervical cancer at least once. The mean score was 5.6 out of 9 (95% CI 5.3-6.0) on the knowledge about cervical cancer and its screening and 6.3 out of 10 (95% CI 5.9-6.6) on cervical cancer risk factors, respectively. 84% of women agreed that cervical cancer is a life-threatening disease, but only 49% agreed that they were at risk for cervical cancer. Facilitators of participating in future cervical cancer screening among women with HIV in Guangxi included family support for related healthcare, trust and openness to conversations with health workers on female health concerns, and convenient transportation. The barriers included knowledge gaps in health awareness, cervical-cancer-related information, and available cervical cancer screening services.

Conclusion: Women with HIV in Guangxi are potentially under-screened for cervical cancer. Designing future cervical cancer screening programs targeting women with HIV in Guangxi should address the knowledge gaps to increase screening uptake and improve outcomes in this high-risk population.

Citation Format: Ran Zhao, Shujia Liang, Deanna Teoh, Yunqing Fei, Xianwu Pang, Shalini Kulasingam. A Comprehensive Survey to Identify Barriers to and Facilitators of Cervical Cancer Screening in Women With HIV in Guangxi, China [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 54.
Abstract 64: The Prevalence of Hepatocellular Carcinoma in HIV-Infection: Results of Large-Scale Liver Ultrasound Screening Program in HIV-Infected Nigerians
Authors: Davwar Pantong , David Nyam , Odeghe Emuobor , Mary Duguru , Hawkins Claudia , Oyeleke Ganiyat , Okeke Edith , Olufunmilayo Lesi , Roberts Lewis , Sagay Atiene , Hou Lifang , Murphy Robert , Imade Godwin
Published: July 2021

Purpose: In Nigeria, over 3 million people are infected with HIV (prevalence rates 6.1-8.0%). Rates of co-infection with HBV and HCV among HIV-infected are common ranging from 9-12.3% (HBV) and 6-20% (HCV). Given the high burden of HIV/HBV co-infection, it is hypothesized that there are high rates of HCC among HIV-infected individuals in Nigeria. This abstract describes the pattern of liver diseases detected by abdominal ultrasound, including abnormalities suggestive of HCC, from a screening program.

Methods: In this cross-sectional study, all consenting adults (>18) HIV-infected subjects underwent an abdominal ultrasound using the N2 full Digital Ultrasound and completed a structured questionnaire. Ultrasonography findings were recorded. Basic descriptive statistics was performed.

Results: Two thousand seven hundred and twenty-seven subjects were enrolled into the program [1950 (71.5%) females; mean age 46.40±10.15 years]. All subjects were receiving antiretroviral therapy (ART). The majority of study subjects (2149, 78.8%) had a normal liver ultrasound scan. The most common liver abnormality was hepatomegaly, seen in 298 (10.9%) of the study subjects. One hundred and nine (4.0%) had a diffusely hyper-echogenic liver, suggestive of fatty liver. Seventy-two (2.6%) had a hypo-echogenic liver with starry sky appearance, suggestive of active inflammation. Thirty-eight (1.4%) of the study subjects had features consistent with liver cirrhosis. Liver nodules or solid masses were seen in 4 (0.01%) of the study subjects. Mean HIV viral load was significantly higher among those with hepatomegaly compared to those with a normal scan (log103.74 vs.log105.21 p=0.015).

Conclusion: The prevalence of HCC among HIV-infected was extremely low 4(0.01%). This is reassuring given the relatively large number of subjects screened and high prevalence of other risk factors for HCC in this population. An effect of ART on reducing incidence of HCC in this population is surmised, however, requires further exploration in long-term follow up studies.

Citation Format: Pantong Davwar, Nyam David, Emuobor Odeghe, Duguru Mary, Claudia Hawkins, Ganiyat Oyeleke, Edith Okeke, Lesi Olufunmilayo, Lewis Roberts, Atiene Sagay, Lifang Hou, Robert Murphy, Godwin Imade. The Prevalence of Hepatocellular Carcinoma in HIV-Infection: Results of Large-Scale Liver Ultrasound Screening Program in HIV-Infected Nigerians [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 64.
Abstract 67: Quantifying Transportation Barriers in Rwandan Patients Seeking Treatment for Breast Cancer
Authors: Fadelu Temidayo , Nguyen Cam , Nsabimana Nicaise , Bigirimana Evariste , Mukandayisenga Vestine , Tuyishime Hubert , Shulman Lawrence , Rebbeck Timothy
Published: July 2021

Purpose: Comprehensive cancer care in many sub-Saharan African countries is concentrated within a few centers. With only two comprehensive treatment facilities in Rwanda, travel distance, travel time, and travel cost may represent underappreciated barriers to accessing cancer treatment. Here we describe travel and transportation experiences of patients receiving curative breast cancer treatment at Butaro Cancer Center of Excellence (BCCOE).

Methods: A cross-sectional telephone survey assessing contributors of care-continuum delays was administered to female patients receiving curative breast cancer treatment. Between July and November 2020, 89 (75%) of eligible patients were reached by phone, all of whom provided verbal consent and voluntarily participation. Patient demographic information and transportation experience were descriptively summarized.

Results Participants had a median age of 48 years, and they represented all five Rwandan provinces. Twenty-one patients (24%) belonged to the lowest of the four socioeconomic “ubudehe” strata, as defined by the local government, while none were in the highest stratum. Few patients' households owned transportation vehicles with only one owning a private car, 4 (4%) owning a motorbike, and 23 (26%) owning a bicycle. Most patients, 84 (94%) utilized public transport buses for a portion of their travel, while 48 (54%) utilized motorbikes. Median one-way travel time from patients' home to BCCOE was 7 hours (interquartile range: 6-8 hours). The median cost of transportation for each round-trip was RWF12000, approximately $12 USD, which equates to 75% of a Rwandan adult's total monthly consumption. Transportation costs were noted as a significant barrier by 43 patients (46%), and 35 (39%) received financial support from outside their household to pay for transportation.

Conclusion Transportation time and cost are significant burdens on patients receiving breast cancer treatment in Rwanda. Studies are needed to evaluate strategies for alleviating these burdens, such as comprehensive transportation financial support and innovative care delivery with telemedicine.

Citation Format: Temidayo Fadelu, Cam Nguyen, Nicaise Nsabimana, Evariste Bigirimana, Vestine Mukandayisenga, Hubert Tuyishime, Lawrence Shulman, Timothy Rebbeck. Quantifying Transportation Barriers in Rwandan Patients Seeking Treatment for Breast Cancer [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 67.
Abstract 69: To Triage or Not? Positive Predictive Value of Visual Inspection with Acetic Acid for Diagnosis of Cervical Intraepithelial Neoplasia Grade 2 or Worse (CIN2+) among HIV-Positive Women in a Low-Resource Setting
Authors: Mungo Chemtai , Ogollah Cyrillus , Ambaka Jennifer , Randa Magdalene , Omoto Jackton , Cohen Craig
Published: July 2021

Purpose: The World Health Organization (WHO) recommends human papillomavirus (HPV) as a primary screening test within "screen-and-treat" cervical cancer programs in low- and middle-income countries (LMICs). Following a positive test, two alternative strategies are endorsed within the single-visit approach. All HPV positive women can be offered immediate treatment, or visual inspection with acetic acid (VIA) is used to triage. Thus, we calculated the positive predictive value (PPV) of VIA for histologically confirmed CIN2+ among HPV-positive women living with HIV (WLWH).

Methods: Between August 2019 and March 2020, as part of a clinical trial (NCT04191967) in western Kenya, high-risk HPV-positive WLWH age 25-65 years underwent VIA and colposcopy-directed biopsies regardless of VIA result. All women received treatment. The PPV of VIA for CIN2+ was determined.

Results: Three hundred and sixty-six HPV-positive WLWH were evaluated during the study period. Mean age was 40.2 years (SD 8.5), median CD4 count was 420 (IQR 359), and 94.5% were virally suppressed. Seventy-four (20.2%) women had CIN2+ on histology (14 CIN2, 54 CIN3, six microinvasive carcinoma), of whom only 33 were also VIA-positive. The PPV of VIA for diagnosis of CIN2+ was 44.6% (95% CI 33.0 – 56.6) and was similar when limited to CIN3+. The PPV decreased with age, ranging from 72.7% (95% CI 54.5–86.7), to 24.2% (95% CI 11.1 – 42.3) to 3.0% (95% CI 0.1 – 15.8) among ages 30-39 years, 40-49 years, and 50 years and greater, respectively.

Conclusions: While HPV testing has low specificity among WLWH, triage with VIA has a low positive predictive value for CIN2+ and would result in missed opportunities for treatment in this high-risk population. This highlights the need for more objective, affordable, and accessible triage tests, e.g. artificial intelligence-assisted cervicography or biomarkers of dysplasia to improve the PPV of the HPV-based screen-and-treat single-visit approach in LMICs.

Citation Format: Chemtai Mungo, Cyrillus Ogollah, Jennifer Ambaka, Magdalene Randa, Jackton Omoto, Craig Cohen. To Triage or Not? Positive Predictive Value of Visual Inspection with Acetic Acid for Diagnosis of Cervical Intraepithelial Neoplasia Grade 2 or Worse (CIN2+) among HIV-Positive Women in a Low-Resource Setting [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 69.
Abstract 75: Cost-effectiveness Analysis of CHOP and R-CHOP Treatment of Diffuse Large B-cell Lymphoma in Malawi
Authors: Painschab Matthew , Kohler Racquel , Kimani Stephen , Wheeler Stephanie , Gopal Satish
Published: July 2021

Purpose: Cost-effectiveness data for cancer treatment are needed from sub-Saharan Africa (SSA), where diffuse large B-cell lymphoma (DLBCL) is a common, curable cancer. In high-income countries, the standard of care for DLBCL is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemoimmunotherapy. Rituximab is often not available in SSA due to cost, and treatment with CHOP is common.

Methods: We evaluated the cost-effectiveness of DLBCL treatment using Malawi-specific data. Clinical data were from a prospective observational cohort treated with CHOP, as well as a clinical trial of R-CHOP. We used a decision-tree model to calculate costs per disability adjusted life year (DALY) averted from the health system perspective and estimated a willingness to pay (WTP) threshold of three times GDP per capita.

Results: On a per-patient level, compared to no chemotherapy, CHOP is estimated to avert 7·9 DALYS, at an incremental cost of $1,500, for an incremental cost-effectiveness ratio (ICER) of $194 per DALY averted, which is well below WTP. In probabilistic sensitivity analysis, CHOP was cost-effective for DLBCL in >99% of simulations. Compared to CHOP, R-CHOP is estimated to avert 2·9 DALYs, at an incremental cost of $3,198 and ICER of $1,104 per DALY averted, which is at the WTP threshold and was below WTP in 45% of simulations.

Conclusion: CHOP is cost-effective for DLBCL in Malawi, and the addition of rituximab may be cost-effective. Future studies in SSA and other LMIC settings should include rigorous economic evaluation to promote continued cancer treatment investments and prioritization.

Citation Format: Matthew Painschab, Racquel Kohler, Stephen Kimani, Stephanie Wheeler, Satish Gopal. Cost-effectiveness Analysis of CHOP and R-CHOP Treatment of Diffuse Large B-cell Lymphoma in Malawi [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 75.
Abstract 82: Confirmation and Identification of Incident Cases of Breast Cancer in a Setting with Limited Cancer Registry Coverage: The Mexican Teachers' Cohort
Authors: Gómez-Flores-Ramos Liliana , Brochier Marion , Cortés-Valencia Adrian , Lozano-Esparza Susana , Solís Aura Erazo Valle , Méndez Aureliano Plácido , Ontiveros Olga Rosalinda Rivera , Núñez Alberto Cundapí , Méndez Angélica Pon , Lajous Martín
Published: July 2021

Purpose: To present the use of administrative databases and registries to confirm and identify incident breast cancer (BC) cases in a prospective cancer cohort in Mexico where cancer registry coverage is limited.

Methods: The Mexican Teacher's Cohort (MTC) was established in 2006-2008 when 115,314 female teachers residing in a 12-state area in Mexico (cancer registry coverage, 13%) responded to a questionnaire on reproductive, lifestyle factors, and medical conditions. We projected 955 BC incident cases by the end of 2019. Study participants reported new BC diagnoses in follow-up questionnaires between 2008 and 2020. Self-reports were confirmed by directly contacting participants. Administrative (one medical claims database, two reimbursement databases, and electronic medical records from two institutions) and population-based cancer registry data were used to confirm previously self-reported BC and identify additional cases. Two independent national mortality registries were used to identify BC deaths (2006-2018).

Results: We have identified 632 self-reported cases and confirmed 300 through participant contact or presence in a database. We additionally identified and confirmed 100 cases from administrative databases, 25 from cancer registries, and 94 from mortality registries. Median age at diagnosis was 49.0 (± SD 6.9), 63.2% (n=538) of the cases were pre-menopausal and 4.8% (n=41) occurred in indigenous women. Thus far, we have identified 89% (n=851) of the projected number of BC cases by the end of 2019 and confirmed 60.8% (n=518). We know the treating hospital for 30.0% (n=255) of the total cases and obtained histopathology reports from 12.0% (n=62) of the confirmed cases.

Conclusion: Leveraging administrative databases for confirmation and identification of incident BC cases is feasible in the MTC. Low- and middle-income countries with limited cancer registry coverage seeking to develop prospective cancer cohorts should explore the use of administrative databases to confirm and identify incident cancer cases.

Citation Format: Liliana Gómez-Flores-Ramos, Marion Brochier, Adrian Cortés-Valencia, Susana Lozano-Esparza, Aura Erazo Valle Solís, Aureliano Plácido Méndez, Olga Rosalinda Rivera Ontiveros, Alberto Cundapí Núñez, Angélica Pon Méndez, Martín Lajous. Confirmation and Identification of Incident Cases of Breast Cancer in a Setting with Limited Cancer Registry Coverage: The Mexican Teachers' Cohort [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 82.
Abstract 88: Clinical Characteristics of Incident Lymphoma in Malawi before and after Implementation of Universal ART
Authors: Gondwe Yolanda , Kudowa Evaristar , Painschab Matthew , Tomoka Tamiwe , Fedoriw Yuri , Kasonkanji Edwards , Kaimila Bongani , Zuze Takondwa , Mithi Victor , Mumba Noel , Kimani Stephen , Mulenga Maurice
Published: July 2021

Purpose: In 2016, Malawi expanded eligibility for antiretroviral therapy (ART) to anyone with confirmed HIV infection. Here, we assess the impact on lymphoma presentation.

Methods: We enrolled patients with newly diagnosed lymphoproliferative disorders 2013-2020. We categorized patients pre-universal ART (pre-UART) (2013-June 2016) or post-universal ART (post-UART) (July 2016-2020) and evaluated clinical characteristics.

Results: There were 157 cases pre-UART and 256 post-UART. The most common diagnoses were diffuse large B-cell lymphoma (DLBCL) (43%), low-grade lymphoma (12%), Burkitt lymphoma (10%), Hodgkin lymphoma (9%), and multicentric Castleman disease (7%). HIV prevalence was 50%, mean age 43, and 62% male. 66% of pre-UART HIV+ knew their HIV status, for median 5 years (IQR 2-8), and 53% were on ART for median 4 years (IQR 2-7). 80% of post-UART HIV+ knew their HIV status (p=0.02), for median 4 years (IQR 2-9) and 70% were on ART for median 4 years (IQR 2-8). HIV was suppressed <1000 copies/mL in 56% (n=33/59) pre-UART and 71% (n=73/103) post-UART (p=0.05). Among DLBCL, 61% (n=23/38) of pre-UART HIV+ knew their HIV status, for median 5 years (IQR 2-9), and 46% were on ART for median 4 years (IQR 2-6). 82% (n=51/62) of post-UART DLBCL HIV+ knew their HIV status (p=0.02), for median 5 years (IQR 2-9) and 68% were on ART for median 5 years (IQR 2-9). Post-UART DLBCL patients had median HIV viral load of 0 log copies/mL (IQR 0-10) compared to pre-UART (6.2 log copies/mL, IQR 0-10) (p=0.09). CD4 count, age adjusted-IPI and Ki67 proliferation index were similar between DLBCL in the two groups.

Conclusion: There were no significant differences in lymphoma subtypes diagnosed or in traditional DLBCL prognostic factors after implementation of universal ART in Malawi. However, HIV was better controlled in the post-UART period and differences in immunological status may have implications for therapy and prognosis.

Citation Format: Yolanda Gondwe, Evaristar Kudowa, Matthew Painschab, Tamiwe Tomoka, Yuri Fedoriw, Edwards Kasonkanji, Bongani Kaimila, Takondwa Zuze, Victor Mithi, Noel Mumba, Stephen Kimani, Maurice Mulenga. Clinical Characteristics of Incident Lymphoma in Malawi before and after Implementation of Universal ART [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 88.
Abstract 94: Mammographic Density in Middle to Low Breast Cancer Incidence Settings: DDM-Colombia
Authors: Pedraza-Flechas Ana , Gaitan Sandra , Estrada Kelly , Camargo Julian , Castillo Adriana , Gonzalez Tania , Gonzalez Martha , Pinzón-Rondon Ángela , Ruíz-Sternberg Ángela , Pollán Marina , Perez-Gómez Beatriz
Published: July 2021

Purpose: Mammographic density (MD) is a potential risk factor for breast cancer, which could be key to monitor prevention strategies and to detect high risk population. MD has been widely studied in high income countries; but not in countries of lower income levels. The aim of this study was to explore the determinants of MD among Colombian women (DDM-Colombia).

Methods: Cross sectional study in women aged 40-72 years recruited consecutively in a private BC screening unit in Bogotá-Colombia, 2019-2020. Personal history and anthropometric measures were collected the same day that patients went to their mammogram exams. The study was approved by Fundación Sanitas' IRB. All patients agreed to join the study and signed the informed consent. A trained researcher estimated the percentage of MD using a validated semiautomatic computer tool (DM-scan). The differences in MD by menopausal status were analysed in a linear regression model adjusted by age, body mass index (BMI) and reproductive factors.

Results: Preliminary results show the characteristics of 687 women (75 Premenopausal, 612 peri/postmenopausal). The mean age of the participants was 58 years (standard deviation (SD): 6.2) and the mean BMI was 27.6 (SD: 4.4). The overall percentage of MD was 25.3 (95% Confidence Interval (CI): 24.3 to 26.4); the percentage of MD in peri/postmenopausal was 9.6 points lower (CI: 6.3%-12.9) compare to premenopausal women.

Conclusions: High MD prevalence is less common in Colombian women compared to high income countries. It is necessary to continue studying MD prevalence and determinants in this population, to assess the need to develop different prevention strategies for them. Funding: Ministerio de Ciencia Tecnología e Innovación Colombiano 122280764284 (771-2018).

Citation Format: Ana Pedraza-Flechas, Sandra Gaitan, Kelly Estrada, Julian Camargo, Adriana Castillo, Tania Gonzalez, Martha Gonzalez, Ángela Pinzón-Rondon, Ángela Ruíz-Sternberg, Marina Pollán, Beatriz Perez-Gómez. Mammographic Density in Middle to Low Breast Cancer Incidence Settings: DDM-Colombia [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 94.
Optineurin Guards IFNγ Signaling in Cancer Cells
Authors: Salvagno Camilla , Cubillos-Ruiz Juan R.
Published: July 2021

In this issue, Du and colleagues uncover that optineurin functions as a key regulator of IFNγ receptor (IFNGR1) stability in malignant cells. Loss of optineurin in colorectal cancer cells causes IFNGR1 degradation, leading to impaired IFNγ signaling, decreased MHC-I expression, and enhanced ability to evade adaptive immune control.

See related article by Du et al., p. 1826.
Triple Therapy to Outwit the BRAF Oncogene
Authors: Zhang Chao , Bollag Gideon
Published: July 2021

BRAF-mutant cancers have been knocked down by BRAF and MEK inhibitor combos, yet the cancers always find a way to get back up. Adding a third medicine, namely, a dimer-selective BRAF inhibitor, can knock down longer and better.

See related article by Adamopoulos et al., p. 1716.
Relationship between Renal Damage and Serum Complement C3 in Children with Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Authors: Zhang Pei , Yang Xiao , He Xu , Hu Jian , Gao Chun-Lin , Xia Zheng-Kun
Published: July 2021

Background: Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) disease is a well-known antibody-induced autoimmune disease. The pathogenesis of AAV has not yet been completely clarified, but may be related to heredity, infection, environmental factors, cellular immunity, etc. In recent years, complement in AAV pathogenesis has become the latest research hotspot, and the decrease of serum complement C3 is associated with poor prognosis of anti-neutrophil cytoplasmic antibody-associated glomerulonephritis. In the current study, we investigated the associations between serum complement C3 and kidney injury in AAV children. Methods: Twenty-four children with AAV admitted to our hospital from June 2014 to June 2019 were divided into the low C3 group and the normal C3 group. All the children have undergone renal biopsy. The clinical manifestations, laboratory tests, renal pathology, treatment, and prognosis of the 2 groups were observed. The primary end point was end-stage renal disease (ESRD). Results: It was shown that kidney injury was more obvious in patients with low C3 than in patients with normal C3 serum. The values of ESR, Scr, and UA before treatment in the low C3 group were higher than those in the normal C3 group (p < 0.01); the values of RBC, Hb, PLT, ALB, LDH, and eGFR in the normal C3 group were higher than those in the low C3 group (p < 0.01). The values of urinary protein and NAG enzyme in the low C3 group were higher than those in the normal C3 group (p < 0.01). The area of glomerular abandonment, sclerosis, segmental sclerosis, crescent, cellular crescent, cellular fibrous crescent, fibrous crescent, segmental loop necrosis, and the number of cases with acute renal tubulointerstitial lesions in the low C3 group were bigger than those in the normal C3 group (p < 0.05 and < 0.01). The number of cases with C3 deposition in the low C3 group was higher than that in the normal C3 group (p < 0.05). The number of patients receiving CRRT and PE in the low C3 group was higher than that in the normal C3 group (p < 0.05 and < 0.01). In this study, 3 children entered the stage of ESRD and 1 died in the low C3 group. Conclusion: The kidney injury of AAV children with low complement C3 is serious, and the prognosis is poor. We should pay attention to the influence of decreased complement C3 on the condition and prognosis of AAV children.
Malignancy Rate and Malignancy Risk Assessment in Different Lesions of Uncertain Malignant Potential in the Breast (B3 Lesions): An Analysis of 192 Cases from a Single Institution
Authors: Mohrmann Svjetlana , Maier-Bode Anna , Dietzel Frederic , Reinecke Petra , Krawczyk Natalia , Kaleta Thomas , Kreimer Ulrike , Antoch Gerald , Fehm Tanja N. , Roth Katrin Sabine
Published: July 2021

Background: The question of how to deal with B3 lesions is of emerging interest. Methods: In the breast diagnostics of 192 patients between 2009 and 2016, a minimally invasive biopsy revealed a B3 lesion with subsequent resection. This study investigates the malignancy rate of different B3 subgroups and the risk factors that play a role in obtaining a malignant finding. Results: The distribution of B3 lesions after minimally invasive biopsy was as follows: atypical ductal hyperplasia (ADH), 7.3%; flat epithelial atypia (FEA), 7.8%; lobular neoplasia (LN), 7.8%; papilloma (Pa), 49.5%; phylloidal tumour (PT), 8.9%; radial sclerosing scar (RS), 3.1%; mixed findings, 10.4%; and other B3 lesions, 5.2%. Most B3 lesions were detected by stereotactic vacuum-assisted biopsy (44.3%), 36.5% by ultrasound-assisted biopsy, and 19.3% by magnetic resonance imaging-assisted biopsy. Most B3 lesions (55.2%) were verified by surgical resection, whereas 30.7% were downgraded to a benign lesion. About 14.1% of the cases were upgraded to malignant lesions, 9.4% to ductal carcinoma in situ and 4.7% to invasive carcinoma. In relation to individual B3 lesions, the following malignancy rates were found: 28.6% (ADH), 13.3% (FEA), 33.3% (LN), 12.6% (Pa), 5.9% (PT), and 0% (RS). The most important risk factor was increasing age. Postmenopausal status was considered an increased risk for an upgrade (p = 0.015). A known malignancy in the ipsilateral breast was a significant risk factor for a malignant upgrade (p = 0.003). Conclusion: Increasing knowledge about B3 lesions allows us to develop a “lesion-specific” therapy approach in the heterogeneous group of B3 lesions, with follow-up imaging for some lesions with less malignant potential and concordance with imaging or further surgical resection in cases of disconcordance with imaging or higher malignant potential.
Progredienzangst entlang der Überlebensspanne: Ergebnisse einer Befragung erwachsener Langzeit-Krebsüberlebender
Authors: Fugmann Dominik , Karger André
Published: July 2021

Objective: Our study analysed fear of cancer recurrence (FoR) in long-term cancer survivors in relation to medical variables, depression, anxiety, and quality of life. Methods: We present data obtained from 1,002 cancer survivors (53% male, mean age = 68 years, 26% prostate cancer, 22% breast cancer) across all cancer types 5 (N = 660) and 10 (N = 342) years after diagnosis, who were recruited via a large Clinical Cancer Registry in Germany in a cross-sectional study. FoR, depression, and anxiety were measured using validated self-report questionnaires (12-item short version of the Fear of Progression Questionnaire [FoP-Q-SF], Patient Health Questionnaire-9 [PHQ-9[, and General Anxiety Disorder-7 [GAD-7]). Hierarchical regression models were carried out with FoR as dependent variable and time since diagnosis as control variable. Results: We found high FoR-values in 17% of the cancer survivors (FoP-Q-SF total score>33). FoR was higher in the 5-year cohort (P = .028, d = 0.153). Cancer survivors were most worried about the future of the family; they report being nervous prior to doctor’s appointment and being afraid of relying on strangers help. Higher FoR was related to female gender (Beta = .149, P<.001), younger age (Beta = -.103, P<.001), low social (Beta = -.129, P<.001) and emotional functioning (Beta = -.269, P<.001), received hormone therapy (P = .025, d = 0.056), and high anxiety levels (Beta = .227, P<.001). Conclusions: Even though FoR declines slightly over time, it is still a common mental health problem for long-term survivors even 10 years after cancer diagnosis. Since FoR is associated with reduced emotional and social quality of life, patients who are at greater risk of experiencing FoR must be identified and supported. Particularly at risk are younger women who received hormone therapy.
Long-Term Incidence of Stroke and Dementia in ASCOT
Authors: Whiteley William N. , Gupta Ajay K. , Godec Thomas , Rostamian Somayeh , Whitehouse Andrew , Mackay Judy , Sever Peter S.
Published: July 2021

Background and Purpose:

Management of stroke risk factors might reduce later dementia. In ASCOT (Anglo-Scandinavian Outcome Trial), we determined whether dementia or stroke were associated with different blood pressure (BP)–lowering regimens; atorvastatin or placebo; and mean BP, BP variability, and mean cholesterol levels.

Methods:

Participants with hypertension and ≥3 cardiovascular disease risk factors were randomly allocated to amlodipine- or atenolol-based BP-lowering regimen targeting BP <140/90 mm Hg for 5.5 years. Participants with total cholesterol ≤6.5 mmol/L were also randomly allocated to atorvastatin 10 mg or placebo for 3.3 years. Mean and LDL (low-density lipoprotein) cholesterol, BP, and SD of BP were calculated from 6 months to end of trial. UK participants were linked to electronic health records to ascertain deaths and hospitalization in general and mental health hospitals. Dementia and stroke were ascertained by validated code lists and within-trial ascertainment.

Results:

Of 8580 UK participants, 7300 were followed up to 21 years from randomization. Atorvastatin for 3.3 years had no measurable effect on stroke (264 versus 272; adjusted hazard ratio [HR], 0.92 [95% CI, 0.78–1.09];
P
=0.341) or dementia (238 versus 227; adjusted HR, 0.98 [95% CI, 0.82–1.18];
P
=0.837) compared with placebo. Mean total cholesterol was not associated with later stroke or dementia. An amlodipine-based compared with an atenolol-based regimen for 5.5 years reduced stroke (443 versus 522; adjusted HR, 0.82 [95% CI, 0.72–0.93];
P
=0.003) but not dementia (450 versus 465; adjusted HR, 0.94 [95% CI, 0.82–1.07];
P
=0.334) over follow-up. BP variability (SD mean BP) was associated with a higher risk of dementia (per 5 mm Hg HR, 1.14 [95% CI, 1.06–1.24];
P
<0.001) and stroke (HR, 1.21 [95% CI, 1.12–1.32];
P
<0.001) adjusted for mean BP.

Conclusions:

An amlodipine-based BP regimen reduced the long-term incidence of stroke compared with an atenolol-based regimen but had no measurable effect on dementia. Atorvastatin had no effect on either stroke or dementia. Higher BP variability was associated with a higher incidence of later dementia and stroke.
Reexamination of the Embolic Stroke of Undetermined Source Concept
Authors: Albers Gregory W. , Bernstein Richard , Brachmann Johannes , Camm A. John , Fromm Peter , Goto Shinya , Granger Christopher B. , Hohnloser Stefan H. , Hylek Elaine , Krieger Derk , Passman Rod , Pines Jesse M. , Kowey Peter
Published: July 2021

Occult atrial fibrillation (AF) is a leading cause of stroke of unclear cause. The optimal approach to secondary stroke prevention for these patients remains elusive. The term embolic stroke of undetermined source (ESUS) was coined to describe ischemic strokes in which the radiographic features demonstrate territorial infarcts resembling those seen in patients with confirmed sources of embolism but without a clear source of embolism detected. It was assumed that patients with ESUS had a high rate of occult AF and would benefit from treatment with direct oral anticoagulants, which are at least as effective as vitamin K antagonists for secondary stroke prevention in patients with AF, but with a much lower risk of intracerebral hemorrhage. Two recent large randomized trials failed to show superiority of direct oral anticoagulants over aspirin in ESUS patients. These findings prompt a reexamination of the ESUS concept, with the goal of improving specificity for detecting patients with a cardioembolic cause. Based on the negative trial results, there is renewed interest in the role of long-term cardiac monitoring for AF in patients who fit the current ESUS definition, as well as the clinical implication of detecting AF. Ongoing trials are exploring these questions. Current ESUS definitions do not accurately detect the patients who should be prescribed direct oral anticoagulants, potentially because occult AF is less common than expected in these patients and/or anticoagulants may be less beneficial in patients with ESUS but no AF than they are for patients with stroke with established AF. More specific criteria to identify patients who may be at higher risk for occult AF and reduce their risk of subsequent stroke have been developed and are being tested in ongoing clinical trials.
A Struggle for Identity: The Ismailis in the Afghan War (1979-1989)
Authors: Arakelova Victoria , Khachaturian Nelli
Published: July 2021

The paper is a part of a wider research on the Ismaili identity, peculiarities of the Ismailis’ self-identification in various parts of the world under different historical circumstances. The ambiguous status of the Ismailis in Afghanistan turned to be particularly problematic by the end of the 19th century when the Pashtuns became dominant in the traditionally Ismaili-inhabited areas. In a hostile milieu, under severe persecutions, the local Ismaili identity acquired a tendency of unification with other ethno-religious identities, the principle of taqiyya having been widely spread. Since then, the Ismailis became especially dependent on the political situation in Afghanistan and the policy of its rulers towards ethnic and religious minorities. The War of 1979-1989 turned to be the most dramatic episode in the history of the Ismaili community in Afghanistan when its very survival appeared to be questioned: Ismaili intellectuals left the region, and lower social layers got involved in drug cultivation and trafficking. Supporting any of the conflict’s sides could have led to a community tragedy, possibly to its complete annihilation. The limited information we obtained, including the memoirs of the Afghan War veterans, demonstrate the identity split in the Ismaili community of Afghanistan whose members were fighting on the opposite sides of the armed conflict.
Who’s Afraid of Religious Extremism?
Authors: Shestopalets Denys
Published: July 2021

This article explores the dynamics of competition between Muslim organisations in Ukraine after the eruption of the Russian–Ukrainian crisis in March 2014. In particular, it deals with the issue of religious extremism as another ideological fault line between two main centres of Islamic religious authority, the Spiritual Administration of Muslims of Ukraine (SAMU) and the Spiritual Administration of Muslims of Ukraine ‘Umma’ (SAMU-Umma). Although these structures agreed that Islam as a religion should be completely dissociated from all manifestations of extremism and terrorism, their inherent theological and cultural differences led to the SAMU and the SAMU-Umma adopting mutually exclusive discursive strategies for achieving this goal.
The natural anti-inflammatory sesquiterpene lactone achillolide A reduces atopic dermatitis in a murine model
Authors: Telerman Alona , Kashman Yoel , Ofir Rivka , Elmann Anat
Published: July 2021

Plant-derived substances have been shown to affect potential targets in inflammatory diseases. We have previously purified from the desert plant Achillea fragrantissima, a sesquiterpene lactone named achillolide A, and demonstrated its anti-inflammatory activities in cultured brain macrophages named microglial cells. In the present study, we further investigated achillolide A in alleviating atopic dermatitis, a chronic and recurring inflammatory skin disease. We investigated achillolide A for its in vivo anti-inflammatory activity using the oxazolone model of atopic dermatitis in mice, in which oxazolone induces ear swelling. Our results show that mice treated with achillolide A showed a significant decrease in the oxazolone-induced ear swelling. Since macrophages are inflammatory cells that play a pivotal role in the pathogenesis of atopic dermatitis, the anti-inflammatory effects of achillolide A were also studied in spleen cells. We demonstrated that achillolide A reduced the levels of LPS-induced inflammatory cytokines IL-2, IL-6, TNFα, IFNγ and IL-12 that were secreted from cultured splenocytes. These data suggest that achillolide A should be considered for further research in treating atopic dermatitis.
The Inclusion of Sexual Orientation and Gender Identity in Relationships Education
Authors: Johnson Paul , Falcetta Silvia
Published: July 2021

All primary schools in England are under a statutory requirement to provide ‘relationships education’, which includes ‘lgbt content’. The inclusion of content relating to sexual orientation and gender identity has attracted faith-based opposition. Such opposition, which is based on assertions about relationships education interfering with the right of parents to ensure that the education of their children is in conformity with their religious convictions, is likely to lead to legal action in the English courts and perhaps the European Court of Human Rights. This article anticipates the claims that would be made in any such legal action and critically interrogates them through the lens of the European Convention on Human Rights.
Taxonomic and nomenclatural notes on Jacobaea othonnae (Asteraceae—Senecioneae—Senecioninae)
Authors: SUTORÝ KAREL
Published: July 2021

Jacobaea othonnae (M. Bieb.) C.A. Mey., formerly Senecio othonnae M. Bieb., is distributed from the Balkan Peninsula through Anatolia up to the Caucasus and the northern Iranian mountains. On the basis of the variability of its indumentum, its subdivision into three subspecies is proposed. A new subsp. adamsii is described from the eastern part of the distribution range, and a new combination (subsp. anomala) is established for a subspecies narrowly distributed in Greece. Lectotypes for Senecio othonnae, Cacalia anomala and Senecio rariflorus are designated.
Taxonomic study of the genus Eloeophila Rondani, 1856 of Japan (Limoniidae, Diptera)
Authors: KATO DAICHI
Published: July 2021

Japanese species of the genus Eloeophila are revised. Five new species, E. apicisetula sp. nov., E. canidorsalis sp. nov., E. enischnophallus sp. nov., E. hadrophallus sp. nov., and E. tergilobellus sp. nov. are described. One subspecies and two species are synonymized, E. subaprilina yezoensis (Alexander, 1924) with the nominotypical subspecies, E. hidana (Alexander, 1970) with E. persalsa (Alexander, 1940), and E. mishimai (Alexander, 1969) with E. kintaro (Alexander, 1957). Images of the habitus and wings, and drawings of the male terminalia of the Japanese species are shown. Distributions and a key to the Japanese species are provided.
Integrative taxonomy base on morphology and molecular phylogeny with description of a new genus, Progoniogryllus gen. nov. and two new species (Orthoptera: Grylloidea: Gryllidae; Gryllinae)
Authors: MA LIBIN , JING XUAN , ZHENG YANNA
Published: July 2021

Based on both morphological characters and phylogenetic relationships, one new genus Progoniogryllus gen. nov. and two new species, Progoniogryllus rotundus sp. nov. and Progoniogryllus directus sp. nov., are proposed. The new genus is compared with similar genera of Gryllodes Saussure, 1874, Parasongella Otte, 1987, Callogryllus Sjöstedt, 1910 and Goniogryllus Chopard. 1936 by morphological and phylogenetic methods. Based on the knowledge so far, the new genus is very close to Goniogryllus. All the new taxa are described and illustrated, and some information on mating behavior of the new was also provided.
Stability, natural rights, and the limits of prudence
Authors: Anderson Matthew Lee
Published: July 2021

This essay investigates Prof. Nigel Biggar’s critique of natural rights and his subsequent reliance upon “prudence” to secure positive rights for citizens. It offers a modest defense of natural rights as explanatory for certain intuitions, while raising questions about whether positive rights are sufficiently stable on Prof. Biggar’s view.