Detecting cervical precancer and reaching underscreened women by using HPV testing on self samples: updated meta-analyses

hrHPV testing with an appropriate assay offers a promising new strategy that could increase population coverage substantially

What is already known on this topic

  • Tests performed on self samples are less sensitive and less specific than tests performed on clinician samples when using a high-risk human papillomavirus (hrHPV) assay based on signal amplification
  • Response rates for hrHPV testing are higher for self sampling kits than for conventional invitations

What this study adds

  • Tests performed on self samples are similarly sensitive and slightly less specific than tests performed on clinician samples when using a hrHPV assay based on polymerase chain reaction
  • Response rates for hrHPV testing continue to be higher for self sampling kits than for conventional invitations

2018 Study Abstract

Objective
To evaluate the diagnostic accuracy of high-risk human papillomavirus (hrHPV) assays on self samples and the efficacy of self sampling strategies to reach underscreened women.

Design
Updated meta-analysis.

Data sources
Medline (PubMed), Embase, and CENTRAL from 1 January 2013 to 15 April 2018 (accuracy review), and 1 January 2014 to 15 April 2018 (participation review).

Review methods
Accuracy review: hrHPV assay on a vaginal self sample and a clinician sample; and verification of the presence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) by colposcopy and biopsy in all enrolled women or in women with positive tests. Participation review: study population included women who were irregularly or never screened; women in the self sampling arm (intervention arm) were invited to collect a self sample for hrHPV testing; women in the control arm were invited or reminded to undergo a screening test on a clinician sample; participation in both arms was documented; and a population minimum of 400 women.

Results
56 accuracy studies and 25 participation trials were included. hrHPV assays based on polymerase chain reaction were as sensitive on self samples as on clinician samples to detect CIN2+ or CIN3+ (pooled ratio 0.99, 95% confidence interval 0.97 to 1.02). However, hrHPV assays based on signal amplification were less sensitive on self samples (pooled ratio 0.85, 95% confidence interval 0.80 to 0.89). The specificity to exclude CIN2+ was 2% or 4% lower on self samples than on clinician samples, for hrHPV assays based on polymerase chain reaction or signal amplification, respectively. Mailing self sample kits to the woman’s home address generated higher response rates to have a sample taken by a clinician than invitation or reminder letters (pooled relative participation in intention-to-treat-analysis of 2.33, 95% confidence interval 1.86 to 2.91). Opt-in strategies where women had to request a self sampling kit were generally not more effective than invitation letters (relative participation of 1.22, 95% confidence interval 0.93 to 1.61). Direct offer of self sampling devices to women in communities that were underscreened generated high participation rates (>75%). Substantial interstudy heterogeneity was noted (I2>95%).

Conclusions
When used with hrHPV assays based on polymerase chain reaction, testing on self samples was similarly accurate as on clinician samples. Offering self sampling kits generally is more effective in reaching underscreened women than sending invitations. However, since response rates are highly variable among settings, pilots should be set up before regional or national roll out of self sampling strategies.

Whereas accuracy of new combinations of assays and self sampling devices can be evaluated in a diagnostic setting, acceptance and participation should be shown locally in a screening setting before general roll out.

IMMDS Review listens to Professor Carl Heneghan about Primodos Studies

Independent Medicines and Medical Devices Safety Review Oral Hearing, 27th November 2018

The Independent Medicines and Medical Devices Safety Review is Chaired by Baroness Julia Cumberlege CBE DL.

In February 2018, the Secretary of State for Health and Social Care, the Rt Hon Jeremy Hunt MP, announced a review into how the health system responds to reports from patients about harmful side effects from medicines and medical devices. The announcement in the House of Commons follows patient-led campaigns on the use of the hormone pregnancy test Primodos, anti-epileptic drug sodium valproate and surgical mesh.

About Primodos

  • Read and/or download the full study (free access) Oral hormone pregnancy tests and the risks of congenital malformations: a systematic review and meta-analysis, F1000Research, First published 31 Oct 2018, 7:1725, DOI:10.12688/f1000research.16758.1.
  • Read and/or download the full study (free access) The Primodos components Norethisterone acetate and Ethinyl estradiol induce developmental abnormalities in zebrafsh embryos, nature, Published 13 Feb 2018, DOI:10.1038/s41598-018-21318-9.
  • To read some real stories told by the Primodos victims, go to this post comment section.  Read our posts tagged primodos.

Progéniture Distilbène

Le distilbene a des effets secondaires sur plusieurs générations

Festival de dessins d’humour à Labouheyre ; un DESsin de Pierre Bizalion.

Le Distilbène DES, en savoir plus

IMMDS Review listens to Journalist Jason Farrell about Primodos

Independent Medicines and Medical Devices Safety Review Oral Hearing, 26th November 2018

The Independent Medicines and Medical Devices Safety Review is Chaired by Baroness Julia Cumberlege CBE DL.

In February 2018, the Secretary of State for Health and Social Care, the Rt Hon Jeremy Hunt MP, announced a review into how the health system responds to reports from patients about harmful side effects from medicines and medical devices. The announcement in the House of Commons follows patient-led campaigns on the use of the hormone pregnancy test Primodos, anti-epileptic drug sodium valproate and surgical mesh.

About Primodos

  • Read and/or download the full study (free access) Oral hormone pregnancy tests and the risks of congenital malformations: a systematic review and meta-analysis, F1000Research, First published 31 Oct 2018, 7:1725, DOI:10.12688/f1000research.16758.1.
  • Read and/or download the full study (free access) The Primodos components Norethisterone acetate and Ethinyl estradiol induce developmental abnormalities in zebrafsh embryos, nature, Published 13 Feb 2018, DOI:10.1038/s41598-018-21318-9.
  • To read some real stories told by the Primodos victims, go to this post comment section.  Read our posts tagged primodos.

Screening for rare epigenetic variations in autism and schizophrenia

Additional evidence that rare epivariations likely contribute to the mutational spectra underlying neurodevelopmental disorders

2019 Study Abstract

While many studies have led to the identification of rare sequence variants linked with susceptibility to autism and schizophrenia, the contribution of rare epigenetic variations (epivariations) in these disorders remains largely unexplored.

Previously we presented evidence that epivariations occur relatively frequently in the human genome, and likely contribute to a subset of congenital and neurodevelopmental disorders through the disruption of dosage-sensitive genes.

Here we extend this approach, studying methylation profiles from 297 samples with autism and 767 cases with schizophrenia, identifying 84 and 268 rare epivariations in these two cohorts, respectively, that were absent from 4,860 population controls.

We observed multiple features associated with these epivariations that support their pathogenic relevance, including

  1. a significant enrichment for epivariations in schizophrenic individuals at genes previously linked with schizophrenia,
  2. increased brain expression of genes associated with epivariations found in autism cases compared with controls,
  3. in autism families, a significant excess of epivariations found specifically in affected versus unaffected sibs,
  4. Gene Ontology terms linked with epivariations found in autism, including “D1 dopamine receptor binding.”

Our study provides additional evidence that rare epivariations likely contribute to the mutational spectra underlying neurodevelopmental disorders. Image credit Brigham and Women’s Hospital.

DES DIETHYLSTILBESTROL RESOURCES

IMMDS Review listens to Professor Neil Vargesson about Primodos Studies

Independent Medicines and Medical Devices Safety Review Oral Hearing, 27th November 2018

The Independent Medicines and Medical Devices Safety Review is Chaired by Baroness Julia Cumberlege CBE DL.

In February 2018, the Secretary of State for Health and Social Care, the Rt Hon Jeremy Hunt MP, announced a review into how the health system responds to reports from patients about harmful side effects from medicines and medical devices. The announcement in the House of Commons follows patient-led campaigns on the use of the hormone pregnancy test Primodos, anti-epileptic drug sodium valproate and surgical mesh.

About Primodos

  • Read and/or download the full study (free access) Oral hormone pregnancy tests and the risks of congenital malformations: a systematic review and meta-analysis, F1000Research, First published 31 Oct 2018, 7:1725, DOI:10.12688/f1000research.16758.1.
  • Read and/or download the full study (free access) The Primodos components Norethisterone acetate and Ethinyl estradiol induce developmental abnormalities in zebrafsh embryos, nature, Published 13 Feb 2018, DOI:10.1038/s41598-018-21318-9.
  • To read some real stories told by the Primodos victims, go to this post comment section.  Read our posts tagged primodos.

DES Transgenerational Neurodevelopmental Deficits, 2018 Study

Collaborative on Health and the Environment Webinar, 20 March 2019

Dr. Marianthi-Anna Kioumourtzoglou, Assistant Professor in the Department of Environmental Health Sciences at Columbia University Mailman School of Public Health, describes the study Association of Exposure to Diethylstilbestrol During Pregnancy With Multigenerational Neurodevelopmental Deficits design, statistical analyses, and findings.

References

DES DIETHYLSTILBESTROL RESOURCES

IMMDS Review listens to the Association for Children damaged by Hormone Pregnancy Tests

Independent Medicines and Medical Devices Safety Review Oral Hearing, 26th November 2018

The Independent Medicines and Medical Devices Safety Review is Chaired by Baroness Julia Cumberlege CBE DL.

In February 2018, the Secretary of State for Health and Social Care, the Rt Hon Jeremy Hunt MP, announced a review into how the health system responds to reports from patients about harmful side effects from medicines and medical devices. The announcement in the House of Commons follows patient-led campaigns on the use of the hormone pregnancy test Primodos, anti-epileptic drug sodium valproate and surgical mesh.

About Primodos

  • Read and/or download the full study (free access) Oral hormone pregnancy tests and the risks of congenital malformations: a systematic review and meta-analysis, F1000Research, First published 31 Oct 2018, 7:1725, DOI:10.12688/f1000research.16758.1.
  • Read and/or download the full study (free access) The Primodos components Norethisterone acetate and Ethinyl estradiol induce developmental abnormalities in zebrafsh embryos, nature, Published 13 Feb 2018, DOI:10.1038/s41598-018-21318-9.
  • To read some real stories told by the Primodos victims, go to this post comment section.  Our posts tagged primodos.

Pesticide residues found in 98 percent of Canadian honey samples

Determination of glyphosate, AMPA, and glufosinate in honey by online solid-phase extraction-liquid chromatography-tandem mass spectrometry

A new study is the latest evidence that glyphosate herbicides are so pervasive that residues can be found in foods not produced by farmers using glyphosate.

As U.S. regulators continue to dance around the issue of testing foods for residues of glyphosate weed killers, government scientists in Canada have found the pesticide in 197 of 200 samples of honey they examined, Environmental Health News reports, March 22, 2019.

ABSTRACT

A simple method was developed for the simultaneous determination of glyphosate, its main degradation product (aminomethylphosphonic acid), and glufosinate in honey. Aqueous honey solutions were derivatised offline prior to direct analysis of the target analytes using online solid-phase extraction coupled to liquid chromatography-tandem mass spectrometry. Using the developed procedure, accuracies ranging from 95.2% to 105.3% were observed for all analytes at fortification levels of 5, 50, and 150 μg kg−1 with intra-day precisions ranging from 1.6% to 7.2%. The limit of quantitation (LOQ) was 1 μg kg−1 for each analyte. Two hundred honey samples were analysed for the three analytes with AMPA and glyphosate being most frequently detected (99.0% and 98.5% of samples tested, respectively). The concentrations of glyphosate were found to range from <1 to 49.8 μg kg−1 while those of its degradation product ranged from <1 to 50.1 μg kg−1. The ratio of glyphosate to AMPA was found to vary significantly amongst the samples where both analytes were present above the LOQ. Glufosinate was detected in 125 of 200 samples up to a maximum concentration of 33.0 μg kg−1.

Oxford University study links pregnancy drug Primodos to birth defects

Sky News Exclusive, 27 Nov 2018

A groundbreaking study from Oxford University has linked the pregnancy test drug Primodos to malformations in babies born to mothers who used the drug.

Read Oral hormone pregnancy tests and the risks of congenital malformations.

More information

  • Read and/or download the full study (free access) Oral hormone pregnancy tests and the risks of congenital malformations: a systematic review and meta-analysis, F1000Research, First published 31 Oct 2018, 7:1725, DOI:10.12688/f1000research.16758.1.
  • Read and/or download the full study (free access) The Primodos components Norethisterone acetate and Ethinyl estradiol induce developmental abnormalities in zebrafsh embryos, nature, Published 13 Feb 2018, DOI:10.1038/s41598-018-21318-9.
  • Read some real stories told by the Primodos victims, see this post comment section.