Adrian Spoerri

Research on germline genetic variants relies on enough eligible participants which is difficult to achieve for rare diseases such as childhood cancer. With self-collection kits, participants can contribute genetic samples conveniently from their home. Demographic and clinical factors were identified previously that influenced participation in mailed self-collection. People with pre-existing heritable diagnoses might participate differently in germline DNA collection which might render sampling biased in this group. In this nationwide cross-sectional study, we analysed predictive factors of participation in DNA self-collection including heritable diagnoses. We identified childhood cancer survivors from the Swiss Childhood Cancer Registry for invitation to germline DNA self-sampling in September 2019. Participants received saliva sampling kits by postal mail at their home, were asked to fill them, sign an informed consent, and send them back by mail. Two reminders were sent to non-participants by mail. We compared demographic, clinical, and treatment information of participants with non-participants using univariable and multivariable logistic regression models. We invited 928 childhood cancer survivors in Switzerland with a median age of 26.5 years (interquartile range 19-37), of which 463 (50%) participated. After the initial send out of the sampling kit, 291 (63%) had participated, while reminder letters led to 172 additional participants (37%). Foreign nationality (odds ratio [OR] 0.5; 95%-confidence interval [CI] 0.4-0.7), survivors aged 30-39 years at study versus other age groups (OR 0.5; CI 0.4-0.8), and survivors with a known cancer predisposition syndrome (OR 0.5; CI 0.3-1.0) were less likely to participate in germline DNA collection. Survivors with a second primary neoplasm (OR 1.9; CI 1.0-3.8) or those living in a French or Italian speaking region (OR 1.3; CI 1.0-1.8) tended to participate more. We showed that half of childhood cancer survivors participated in germline DNA self-sampling relying completely on mailing of sample kits. Written reminders increased the response by about one third. More targeted recruitment strategies may be advocated for people of foreign nationality, aged 30-39 years, and those with cancer predisposition syndromes. Perceptions of genetic research and potential barriers to participation of survivors need to be better understood. Biobank: https://directory.bbmri-eric.eu/#/collection/bbmri-eric:ID:CH_HopitauxUniversitairesGeneve:collection:CH_BaHOP Research project: Clinicaltrials.gov: NCT04702321.

Research on germline genetic variants relies on a sufficient number of eligible participants which is difficult to achieve for rare diseases such as childhood cancer. With self-collection kits using saliva or buccal swabs, participants can contribute genetic samples conveniently from their home. We identified determinants of participation in DNA self-collection in this cross-sectional study. We invited 928 childhood cancer survivors in Switzerland with a median age of 26.5 years (interquartile range 18.8-36.5), of which 463 (50%) participated. Foreign nationality (odds ratio [OR] 0.5, 95%-confidence interval [CI] 0.4-0.7), survivors aged 30-39 years at study versus other age groups (OR 0.5, CI 0.4-0.8), and those with a known cancer predisposition syndrome (OR 0.5, CI 0.3-1.0) participated less. Survivors with a second primary neoplasm (OR 1.9, CI 1.0-3.8) or those living in a French or Italian speaking region (OR 1.3, 1.0-1.8) tended to participate more. We showed that half of survivors participate in germline DNA self-sampling relying completely on mailing of sample kits. Foreign nationality, age 30-39 years, and cancer predisposition syndromes were associated with less participation. More targeted recruitment strategies may be advocated for these subgroups. To increase participation in DNA self-sampling, understanding and perceptions of survivors need to be better understood.

Background Childhood cancer and its treatment may lead to many acute and chronic health complications. Related impairment in quality of life, excess in deaths, and accumulated health care costs are relevant. There is a wide inter-individual variability in the type and severity of health complications. Genetic variations are suggested to contribute to individual susceptibility. So far, only few genetic variants have been used to risk-stratify treatment and follow-up care. This study platform aims to identify germline genetic variants associated with acute and late complications of childhood cancer. Methods The Genetic Risks for Childhood Cancer Complications Switzerland (GECCOS) study is a nationwide cohort study. It includes patients and survivors who were diagnosed with childhood cancers or Langerhans cell histiocytosis before age 21 years, were registered in the Swiss Childhood Cancer Registry (SCCR) since 1976 and have consented to the Pediatric Biobank for Research in Hematology and Oncology (BaHOP), Geneva, host of the Germline DNA Biobank Switzerland for Childhood Cancer and Blood Disorders (BISKIDS). BISKIDS is a national biobank for the collection of germline DNA in childhood cancer patients and survivors. GECCOS uses demographic and clinical data from the SCCR and the associated Swiss Childhood Cancer Survivor Study (SCCSS), which contains health-related data of survivors. Phenotypic data consist of objective measurements, health conditions diagnosed by physicians, second primary neoplasms, self-reported and health-related information from participants. Germline genetic samples and sequencing data have been collected in BISKIDS. We will perform gene panel sequencing, whole-exome sequencing, or whole-genome sequencing depending on the research questions. We will perform association analyses to identify genetic variants associated with specified health conditions. We will use clustering and machine-learning techniques and assess multiple health conditions in different models. Discussion GECCOS will serve as an overarching platform to enable genotype-phenotype association analyses on complications associated with childhood cancer and its treatments. Knowledge of germline genetic variants associated with childhood cancer-associated health conditions will help to further individualize cancer treatment and follow-up care, potentially resulting in improved efficacy and reduced side effects, for personalized cancer care. Trial registration Clinicaltrials.gov: NCT04702321

Objective: To determine the spectrum of cancers in AYAs living with HIV in South Africa compared to their HIV negative peers. Design: Cross sectional study with cancer data provided by the National Cancer Registry and HIV data from the National Health Laboratory Service. Setting and participants: The NHLS is the largest provider of pathology services in the South African public sector with an estimated coverage of 80%. The NCR is a division of the NHLS. We included AYAs (aged 10-24 years) diagnosed with cancer by public health sector laboratories between 2004 and 2014 (n=8 479). We included 3 672 in the complete case analysis. Primary and secondary outcomes: We used linked NCR and NHLS data to determine the spectrum of cancers by HIV status in AYAs. We also used multivariable logistic regression to describe the association of cancer in AYAs with HIV, adjusting for age, sex (as appropriate), ethnicity, and calendar period. Due to the large proportion of unknown HIV status we also imputed (post-hoc) the missing HIV status. Results: From 2004-2014, 8 479 AYAs were diagnosed with cancer, HIV status was known for only 45% (n=3812); of those whose status was known, about half were HIV positive (n=1853). AYAs living with HIV were more likely to have Kaposi’s sarcoma (adjusted odds ratio (aOR) 218, 95% CI 89.9-530), cervical cancer (aOR 2.18, 95% CI 1.23-3.89), non-Hodgkin’s lymphoma (aOR 2.12, 95% CI 1.69-2.66), and anogenital cancers other than cervix (aOR 2.73, 95% CI 1.27-5.86). About 44% (n=1 062) of AYAs with HIV related cancers had not been tested for HIV, though they were very likely to have the disease. Conclusions: Cancer burden in AYAs living with HIV in South Africa could be reduced by screening young women for cervical cancer and vaccinating them against human papilloma virus (HPV) infection. Strength and limitations: This is the first nationwide study in South Africa to compare the distribution of cancers in adolescents and young adults (AYAs) by HIV status. The record linkage and the additional results determined from the text mining process ensured that we extracted the maximum available HIV results. We assumed a CD4 count test indicates being HIV positive but CD4 testing maybe performed for other reasons Since this was a population of only AYAs diagnosed with cancer, the odds ratios could be overestimated or underestimated depending on the frequency of the cancer

The impact of South Africa’s high human immunodeficiency virus (HIV) burden on cancer risk is not fully understood, particularly in the context of antiretroviral treatment (ART) availability. We examined national cancer trends and excess cancer risk in people living with HIV (PLHIV) compared to those who are HIV-negative. We used probabilistic record linkage to match cancer records provided by the National Cancer Registry to HIV data provided by the National Health Laboratory Service (NHLS). We also used text search of specific HIV terms from the clinical section of pathology reports to determine HIV status of cancer patients. We used logistic and Joinpoint regression models to evaluate the risk and trends in cancers in PLHIV compared to HIV-negative patients from 2004 to 2014. In sensitivity analysis, we used inverse probability weighting (IPW) to correct for possible selection bias. A total of 329,208 cancer cases from public sector laboratories were reported to the NCR from 2004 to 2014 with the HIV status known for 95,279 (28.9%) cancer cases. About 50% of all the female cancer cases (n = 30,486) with a known status were HIV-positive. PLHIV were at higher risk of AIDS-defining cancers (Kaposi sarcoma [adjusted OR:134, 95% CI:111–162], non-Hodgkin lymphoma [adjusted OR:2.73, 95% CI:2.56–2.91] and, cervix [adjusted OR:1.70, 95% CI:1.63–1.77], conjunctival cancer [adjusted OR:21.5, 95% CI:16.3–28.4] and human papilloma virus (HPV) related cancers (including; penis [adjusted OR:2.35, 95% CI:1.85–2.99], and vulva [adjusted OR:1.94, 95% CI:1.67–2.25]) compared to HIV-negative patients. Analysis using the IPW population yielded comparable results. There is need for improved awareness and screening of conjunctival cancer and HPV-associated cancers at HIV care centres. Further research and discussion is warranted on inclusive HPV vaccination in PLHIV.

Background: With antiretroviral therapy (ART), AIDS-defining cancer incidence has declined and non-AIDS–defining cancers (NADCs) are now more frequent among human immunodeficiency virus (HIV)–infected populations in high-income countries. In sub-Saharan Africa, limited epidemiological data describe cancer burden among ART users.Methods: We used probabilistic algorithms to link cases from the population-based cancer registry with electronic medical records supporting ART delivery in Malawi’s 2 largest HIV cohorts from 2000–2010. Age-adjusted cancer incidence rates (IRs) and 95% confidence intervals were estimated by cancer site, early vs late incidence periods (4–24 and >24 months after ART start), and World Health Organization (WHO) stage among naive ART initiators enrolled for at least 90 days.Results: We identified 4346 cancers among 28 576 persons. Most people initiated ART at advanced WHO stages 3 or 4 (60%); 12% of patients had prevalent malignancies at ART initiation, which were predominantly AIDS-defining eligibility criteria for initiating ART. Kaposi sarcoma (KS) had the highest IR (634.7 per 100 000 person-years) followed by cervical cancer (36.6). KS incidence was highest during the early period 4–24 months after ART initiation. NADCs accounted for 6% of new cancers.Conclusions: Under historical ART guidelines, NADCs were observed at low rates and were eclipsed by high KS and cervical cancer burden. Cancer burden among Malawian ART users does not yet mirror that in high-income countries. Integrated cancer screening and management in HIV clinics, especially for KS and cervical cancer, remain important priorities in the current Malawi context.

Objective: To compare birth weight and weight gain in HIV-exposed, uninfected (HEU) infants up to 24 months old, who enrolled in the Malawian national HIV care clinic (HCC) programme either before or after Option B+ (OB+) was implemented. Design, setting and participants: HIV-exposed infants enrol in the HCC programme as soon as possible after birth and are followed up to at least 24 months old. This analysis includes HEU infants with recorded birth weight, date of birth, gender and at least one follow-up weight measurement from 21 health facilities in central and southern Malawi (January 2010–December 2014). Weight-for-age z scores (WAZ) were derived and compared by birth period using linear regression at birth and mixed effects models for postnatal weight gain up to 24 months old. Results: Of 6845 HEU infants included in this study, 88.5% were born after OB+. The proportion of infants exposed in utero to combination antiretroviral therapy (ART) significantly increased after OB+ was implemented, and infants were exposed to ART for a longer time. There was no significant difference in WAZ at birth (P = 0.654) among HEU infants by birth period, but postnatal weight gain was faster among HEU infants born in the Option B+ period than infants born pre-Option B+. Conclusion: Birth weight was not affected by longer exposure to ART during pregnancy after OB+ was introduced, when weight gain in HEU infants was faster, possibly because their mothers were in better health.