Routine cervical screening by primary HPV testing: early findings in the renewed National Cervical Screening Program

Objectives: To report human papillomavirus (HPV) testing patterns and rates of oncogenic HPV‐positivity for specimens submitted during the first 6 months after the National Cervical Screening Program switched from cytology‐ to primary HPV‐based screening. Design, participants: Retrospective cross‐sectional review of 195 606 specimens submitted for HPV testing, 1 December 2017 – 31 May 2018. Setting: Large community‐based general pathology laboratory in metropolitan Sydney. Main outcome measures: Prevalence of oncogenic HPV types (all, HPV16/18, non‐HPV16/18) by reason for HPV test (primary screening, non‐screening); for oncogenic HPV‐positive women in the age band recommended for primary HPV screening (25–74 years), prevalence of cytologic abnormality and rates of 12‐month follow‐up and colposcopy recommendations. Results: 195 606 samples were received: 157 700 (80.6%) for primary screening, 37 906 (19.4%) for non‐screening tests. Oncogenic HPV was detected in 8.1% of screening tests (95% CI, 7.9–8.2%) and 20.9% of non‐screening tests (95% CI, 20.5–21.3%); 35.5% (95% CI, 34.7–36.4%) of women of recommended screening age with positive oncogenic HPV screening test results also had a cytologic abnormality. The proportion of HPV16/18‐positive samples with high grade abnormality was 15.3% (95% CI, 14.2–16.6%); for samples positive for other oncogenic HPV types, the proportion was 6.3% (95% CI, 5.8–6.8%). Repeat HPV testing after 12 months was recommended for 5.4% (95% CI, 5.3–5.5%) and direct colposcopy for 2.6% (95% CI, 2.5–2.7%) of screened women aged 25–74 years. Conclusions: High grade cytologic abnormalities were more common in women positive for HPV16/18, supporting their higher risk classification. Colposcopy referral rates were higher than during primary cytology‐based testing, as predicted by clinical trial and modelling data. The prevalence of HPV was much higher in non‐screening than in primary screening samples. Our findings indicate the renewed program is performing as expected during the initial HPV screening round

The PRESIDE (PhaRmacogEnomicS In DEpression) Trial: a double-blind randomised controlled trial of pharmacogenomic-informed prescribing of antidepressants on depression outcomes in patients with major depressive disorder in primary care

Abstract Background The evidence for the clinical utility of pharmacogenomic (PGx) testing is growing, and guidelines exist for the use of PGx testing to inform prescribing of 13 antidepressants. Although previous randomised controlled trials of PGx testing for antidepressant prescribing have shown an association with remission of depression in clinical psychiatric settings, few trials have focused on the primary care setting, where most antidepressant prescribing occurs. Methods The PRESIDE Trial is a stratified double-blinded randomised controlled superiority trial that aims to evaluate the impact of a PGx-informed antidepressant prescribing report (compared with standard prescribing using the Australian Therapeutic Guidelines) on depressive symptoms after 12 weeks, when delivered in primary care. Six hundred seventy-two patients aged 18–65 years of general practitioners (GPs) in Victoria with moderate to severe depressive symptoms, measured using the Patient Health Questionnaire-9 (PHQ-9), will be randomly allocated 1:1 to each arm using a computer-generated sequence. Participants and GPs will be blinded to the study arm. The primary outcome is a difference between arms in the change of depressive symptoms, measured using the PHQ-9 after 12 weeks. Secondary outcomes include a difference between the arms in change in PHQ-9 score at 4, 8 and 26 weeks, proportion in remission at 12 weeks, a change in side effect profile of antidepressant medications, adherence to antidepressant medications, change in quality of life and cost-effectiveness of the intervention. Discussion This trial will provide evidence as to whether PGx-informed antidepressant prescribing is clinically efficacious and cost-effective. It will inform national and international policy and guidelines about the use of PGx to select antidepressants for people with moderate to severe depressive symptoms presenting in primary care. Trial registration Australian and New Zealand Clinical Trial Registry ACTRN12621000181808. Registered on 22 February 2021

A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4

Case-parent trios were used in a genome-wide association study of cleft lip with and without cleft palate. SNPs near two genes not previously associated with cleft lip with and without cleft palate (MAFB, most significant SNP rs13041247, with odds ratio (OR) per minor allele = 0.704, 95% CI 0.635-0.778, P = 1.44 × 10-11; and ABCA4, most significant SNP rs560426, with OR = 1.432, 95% CI 1.292-1.587, P = 5.01 × 10-12) and two previously identified regions (at chromosome 8q24 and IRF6) attained genome-wide significance. Stratifying trios into European and Asian ancestry groups revealed differences in statistical significance, although estimated effect sizes remained similar. Replication studies from several populations showed confirming evidence, with families of European ancestry giving stronger evidence for markers in 8q24, whereas Asian families showed stronger evidence for association with MAFB and ABCA4. Expression studies support a role for MAFB in palatal development. © 2010 Nature America, Inc. All rights reserved