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.

Pas de glyphosate dans ma Teucha !!!

Les tampons et serviettes hygiéniques contiennent toujours des résidus chimiques

De nouvelles analyses mettent en évidence la présence récurrente de pesticides et de phtalates dans les protections périodiques féminines malgré les dernières recommandations officielles.

  • Le Billet de Sophia Aram, franceinter, 25 février 2019.
  • Tampons et serviettes : connaître la composition, c’est coton ! 60millions-mag, 2019/02/21.
  • Tampons et protections féminines : un rapport ni alarmant ni rassurant, 60millions-mag, 2018/07/20.
  • Tampons et protections féminines : une réglementation s’impose ! 60millions-mag, 2016/02/23.

US FDA Breast Implant Postapproval Studies

Largest-Ever Study Shows Silicone Breast Implants Associated with Rare Diseases

In the largest study of long-term safety outcomes for patients with breast implants, researchers at The University of Texas MD Anderson Cancer Center have found that silicone implants are associated with some rare diseases, autoimmune disorders and other conditions.

Abstract

Objective:
To analyze the long-term safety and efficacy outcomes of patients with breast implants.

Summary Background Data:
Research is ongoing regarding the safety of silicone breast implants. Despite the number of patients with breast implants followed by United States Food and Drug Administration large postapproval studies (LPAS), this database has not been thoroughly analyzed or reported.

Methods:
This is a multicentered, cohort study. LPAS prospectively monitor long-term implant-related outcomes and systemic harms for silicone/saline implants from 2 manufacturers (Allergan and Mentor) placed for primary/revision augmentation/reconstruction. Systemic harms, self-harm, and reproductive outcomes are compared with normative data. Implant-related complications are analyzed by implant composition and operative indication in the short and long terms.

Results:
LPAS data includes 99,993 patients, 56% of implants were silicone for primary augmentation. Long-term magnetic resonance imaging surveillance is under 5%. Compared with normative data, silicone implants are associated with higher rates of Sjogren syndrome (Standardized incidence ratio [SIR]8.14), scleroderma (SIR 7.00), rheumatoid arthritis (SIR5.96), stillbirth (SIR4.50), and melanoma (SIR3.71). One case of BI-ALCL is reported. There is no association with suicide. In the short term, rupture is higher for saline (2.5% vs. 0.5%, P < 0.001), and capsular contracture higher for silicone (5.0% vs. 2.8%, P < 0.001). At 7 years, reoperation rate is 11.7% for primary augmentation, and 25% for primary/revision reconstruction. Capsular contracture (III/IV) occurs in 7.2% of primary augmentations, 12.7% primary reconstructions, and is the most common reason for reoperation among augmentations.

Conclusions:
This is the largest study of breast implant outcomes. Silicone implants are associated with an increased risk of certain rare harms; associations need to be further analyzed with patient-level data to provide conclusive evidence. Long-term safety and implant-related outcomes should inform patient and surgeon decision-making when selecting implants.

Reference. Press release.

Air pollution linked to higher risk of miscarriage

Acute effects of air pollutants on spontaneous pregnancy loss: a case-crossover study

2019 Study Abstract

Objective
To investigate the relationship between acute exposure to air pollutants and spontaneous pregnancy loss.

Design
Case-crossover study from 2007 to 2015.

Setting
An academic emergency department in the Wasatch Front area of Utah.

Patient(s)
A total of 1,398 women who experienced spontaneous pregnancy loss events.

Intervention(s)
None.

Main Outcome Measure(s)
Odds of spontaneous pregnancy loss.

Result(s)
We found that a 10-ppb increase in 7-day average levels of nitrogen dioxide was associated with a 16% increase in the odds of spontaneous pregnancy loss (odds ratio [OR] = 1.16; 95% confidence interval [CI] 1.01–1.33; P=.04). A 10-μg/m3 increase in 3-day and 7-day averages of fine particulate matter were associated with increased risk of spontaneous pregnancy loss, but the associations did not reach statistical significance (OR3-day average = 1.09; 95% CI 0.99–1.20; P=.05) (OR7-day average = 1.11; 95% CI 0.99–1.24; P=.06). We found no evidence of increased risk for any other metrics of nitrogen dioxide or fine particulate matter or any metric for ozone.

Conclusions
We found that short-term exposure to elevated levels of air pollutants was associated with higher risk for spontaneous pregnancy loss.

Do Harmful Chemicals in Health and Beauty Products Make Uterine Fibroids Grow ?

Phthalates exposure and uterine fibroid burden among women undergoing surgical treatment for fibroids: a preliminary study

A pilot study published in the journal Fertility and Sterility suggests that exposure to certain harmful chemicals called phthalates may lead to an increased burden of fibroids, uterine tumors that can cause heavy bleeding, pain, infertility, and other serious reproductive problems.

2019 Study Abstract

Objectives
To examine the association between phthalate exposure and two measures of uterine fibroid burden: diameter of largest fibroid and uterine volume.

Design
Pilot, cross-sectional study.

Setting
Academic medical center.

Patient(s)
Fifty-seven premenopausal women undergoing either hysterectomy or myomectomy for fibroids.

Intervention(s)
None.

Main Outcome Measure(s)
The diameter of the largest fibroid and uterine dimensions were abstracted from medical records. Spot urine samples were analyzed for 14 phthalate biomarkers using mass spectrometry. We estimated associations between fibroid outcomes and individual phthalate metabolites, sum of di(2-ethylhexyl) phthalate metabolites (∑DEHP), and a weighted sum of anti-androgenic phthalate metabolites (∑AA Phthalates) using linear regression, adjusting for age, race/ethnicity, and body mass index. Fibroid outcomes were also examined dichotomously (divided at the median) using logistic regression.

Results
Most women were of black ethnicity, overweight or obese, and college educated. In multivariable models, higher levels of mono-hydroxyisobutyl phthalate, monocarboxyoctyl phthalate, monocarboxynonyl phthalate, mono(2-ethylhexyl) phthalate, mono(2-ethyl-5-hydroxyhexyl phthalate) (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), ∑DEHP, and ∑AA Phthalates were positively associated with uterine volume. Associations were most pronounced for individual DEHP metabolites (MEHHP, MEOHP, MECPP), ∑DEHP, and ∑AA Phthalates. For example, a doubling in ∑DEHP and ∑AA Phthalates was associated with 33.2% (95% confidence interval 6.6–66.5) and 26.8% (95% confidence interval 2.2–57.4) increase in uterine volume, respectively. There were few associations between phthalate biomarkers and fibroid size.

Conclusions
Exposure to some phthalate biomarkers was positively associated with uterine volume, which further supports the hypothesis that phthalate exposures may be associated with fibroid outcomes. Additional studies are needed to confirm these relationships.

The George Washington University press release.

College women, HPV genotyping and sexual behavior before HPV vaccination

Results from samples stored for a long time

This 2018 study was carried out from 2001 to 2005 in college women from Morelos State University in Mexico. Participants were related to the health science field (Medicine, Pharmacy, Psychology, Biology, and Education).. Students with ≥ 3 sexual partners and who did not use condom had 12.8 higher odds of being HPV positive.

Abstract

HPV is the sexually transmitted agent most common among young people, like college students.

The aim of study was to associate sexual behavior characteristics of women with HPV, detected in genital samples taken before the introduction of the HPV vaccine.

Female students during 2001–2005 donated genital samples and the samples were re-analyzed in 2013 for HPV genotyping by RT-PCR.

The frozen storage of the students’ genital samples allowed the detection of HPV DNA and its genotyping after years of sample collection. HPV prevalence was 22%, HPV16 3.9%, and HPV18 1.1%.

Age, multiple sexual partners and the partner’s age at first sexual intercourse were significantly associated to HPV. Students with ≥ 3 sexual partners and who did not use condom had 12.8 higher odds of being HPV positive.

In this report, we found that students with older partners at first sexual intercourse had a higher possibility of becoming positive for HPV DNA. This is relevant because it has been reported that sexual partner’s age is an important risk factor for HIV infection in homosexual men and it is thought that this is partially due to the low acceptance of condom use by older sexual partners. This behavior could also happen regarding HPV, for heterosexual partners. In fact, we found that 49.0% of the older sexual partners did not use condom, compared with 40.1% of younger sexual partners as reported by participating college women (p = 0.119). Additionally, there was a higher possibility of being positive for HPV DNA in women 26 years old or older, this group reported a higher number of lifetime sexual partners and lower frequency of condom use during last sexual intercourse.

The interaction between the number of sexual partners (main risk factor for HPV exposure) and condom use (barrier against HPV exposure) was clear in the studied population, and even though condom use effectiveness in preventing HPV infection has been inconsistent in cross sectional studies, a review of longitudinal studies shows that it protects against the infection.

Condom use in prevention of Human Papillomavirus infections and cervical neoplasia

Systematic review of longitudinal studies, 2014

HPV and cancer : the condom is much more effective than the vaccine in preventing cancer, including when dysplasias are already present. As a bonus, remember that the condom protects against a whole lot of other unpleasant infections or dangers…

Abstract

Objectives
Based on cross-sectional studies, the data on protection from Human Papillomavirus (HPV) infections related to using male condoms appear inconsistent. Longitudinal studies are more informative for this purpose. We undertook a systematic review of longitudinal studies on the effectiveness of male condoms in preventing HPV infection and cervical neoplasia.

Methods
We searched PubMed using MeSH terms for articles published until May 2013. Articles were included if they studied a change in non-immunocompromized women’s cervical HPV infection or cervical lesion status along with the frequency of condom use.

Results
In total, 384 abstracts were retrieved. Eight studies reported in 10 articles met the inclusion criteria for the final review. Four studies showed a statistically significantly protective effect of consistent condom use on HPV infection and on regression of cervical neoplasia. In the remaining four studies, a protective effect was also observed for these outcomes, although it was not statistically significant.

Conclusions
Consistent condom use appears to offer a relatively good protection from HPV infections and associated cervical neoplasia. Advice to use condoms might be used as an additional instrument to prevent unnecessary colposcopies and neoplasia treatments in cervical screening, and to reduce the risk of cervical cancer.

La contraception chez les adolescents canadiens

Les adolescentes devraient choisir le stérilet avant la pilule, dit la Société canadienne de pédiatrie

Les craintes liées à l’utilisation du stérilet sont des vestiges du siècle dernier, expliquent les pédiatres.

Résumé

Chez les adolescents, la santé sexuelle et reproductive est un aspect important des soins de santé complets. Le présent document de principes fournit des conseils afin de sélectionner des contraceptifs à l’intention des adolescentes et de leur en prescrire, y compris les contraceptifs hormonaux courants (pilule, timbre, anneau et progestatif injectable) et les contraceptifs réversibles à longue durée d’action (CRLDA).

Tel qu’on les utilise habituellement, les CRLDA, qui incluent les implants sous-cutanés (non offerts au Canada) et les contraceptifs intra-utérins, sont beaucoup plus efficaces que les contraceptifs hormonaux.

Le présent document de principes recommande les CRLDA comme contraception de première intention chez les adolescentes canadiennes, tout en soulignant que les dispensateurs de soins doivent collaborer avec les jeunes dans le choix d’un moyen de contraception que celles-ci trouvent acceptable, sécuritaire, efficace et pratique. Des stratégies sont proposées pour éliminer les obstacles à l’adoption et au maintien de la contraception.

Référence. Interview HuffPost Québec. Image Ben White.

POLE-mutated clear cell cervical cancer associated with in-utero diethylstilbestrol exposure

Gynecologic Oncology Reports, Volume 28, Pages 15-17, May 2019

2019 Study Highlights

  • We report a POLE-mutated clear cell cervical cancer associated with in-utero DES.
  • Tumor exhibited increased tumor infiltrating lymphocytes and PD-L1 expression.
  • Patient remains in remission for ≥4 years after standard therapy.
  • POLE mutation confers a phenotype of higher immunogenicity and improved outcome.

Abstract

We report an extraordinary case of a woman, exposed to diethylstilbestrol in utero, who developed clear cell adenocarcinoma of the cervix with a concurrent polymerase-Ɛ (POLE) somatic mutation. The tumor exhibited the classic phenotypic characteristics of POLE-mutated tumors originating from other organs (e.g. the uterus or the colon) including increased tumor infiltrating lymphocytes and high PD-L1 expression and has remained in remission since completion of primary therapy for >4 years. This case highlights the importance of next generation sequencing in unraveling the biology of rare tumors and supports that the presence of a POLE mutation and the associated ultramutated state confers a unique phenotype of higher immunogenicity and possibly improved prognosis in a tissue-agnostic manner, i.e. regardless of the type of cancer where the POLE mutation is present. Image credit bioinfo.

DES DiEthylStilbestrol Resources

L’abstention dans les pathologies obligatoires de l’enfant

Progrès de l’abstention dans la rhino-pharyngite, Luc Perino, 2018

Publié par Luc Perino, médecin généraliste, humeur du 13/12/2018

Dans les années 1920, des pédiatres et radiologues américains notèrent que les nourrissons victimes de fortes rhino-pharyngites avaient un gros thymus. Comme ils ne savaient pas à quoi servait cet organe voué à disparaître à l’âge adulte, ils proposèrent de le détruire par irradiation. Cette pratique barbare devint une nouvelle « norme » médicale pendant plus de trente ans. Puis, constatant la surmortalité chez les dizaines de milliers de nourrissons ainsi traités, on comprit que le thymus était un organe majeur du système immunitaire de l’enfant. On avait pris la conséquence du rhume pour sa cause.
Il est inconvenant de juger nos confrères d’hier avec nos yeux d’aujourd’hui, mais il est parfois difficile de s’en abstenir.

L’activisme des soins pour cette pathologie fréquente n’allait pourtant pas s’arrêter là. On a ensuite réalisé des millions d’adénoïdectomies, opération terrible (souvent sans anesthésie), consistant à enlever les fameuses « végétations » autre organe du système immunitaire propre à l’enfant. Au moment où j’écris, ces opérations sont devenues rares, mais elles se pratiquent encore (avec anesthésie) malgré la preuve de leur inefficacité. Les végétations disparaissent vers l’âge de 6 ans.

Ayant enfin compris que le rhume est une pathologie banale et obligatoire de l’enfant, la médecine s’est concentrée sur sa complication unique : l’otite moyenne aigue. Dès que le tympan était rouge, on considérait qu’il y avait otite et l’on prescrivait des antibiotiques, souvent accompagnés d’antiinflammatoires, et parfois de corticoïdes. Ces « remèdes de cheval » se sont révélés soit inutiles, comme les antibiotiques, soit dangereux, comme les antiinflammatoires et les corticoïdes.

On s’est alors concentré sur les otites chroniques dites « séro-muqueuses », car la trompe d’Eustache reliant le pharynx et l’oreille moyenne est plus perméable chez l’enfant. Les enfants ont décidément beaucoup de particularités ! On a alors pratiqué des paracentèses consistant à perforer le tympan, puis on a posé des drains trans-tympaniques (plus connus sous le nom de « diabolos »). Cette pratique est encore fréquente malgré les preuves accumulées de son inutilité.

Les plus sages des médecins ont fini par ne proposer que du sérum physiologique en pulvérisations nasales et du paracétamol. On ne peut que louer cette sagesse, bien que – nous osons à peine le dire – cela se révèle aussi inutile que tout le reste, à court, moyen ou long terme.

Certains épidémiologistes ont voulu savoir quels étaient les facteurs favorisant ces troubles. Trois d’entre eux se dégagent : le manque de sommeil, l’allaitement artificiel, et un statut social défavorisé. Dans ces trois cas, les remèdes sont ne sont pas vraiment du ressort de la médecine. Et les médecins ne les évoquent pas par peur des représailles.

Il nous faut donc encore attendre pour connaître le grand progrès de l’abstention dans les pathologies obligatoires de l’enfant.

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