Validity of histology for the diagnosis of paediatric coeliac disease: a Swedish multicentre study.

Objective Histological evaluation of intestinal biopsies for the diagnosis of coeliac disease can be challenging and compatible with risk of misdiagnosis. The aim was to evaluate the agreement of pathological diagnosis for coeliac disease in children investigated at four major paediatric university hospitals in Sweden. Materials and methods Intestinal duodenal biopsies were collected from 402 children at median 9.7 years (1.4-18.3 years). A pathologist at each hospital performed the primary evaluation. A designated pathologist, blinded to the primary evaluation, performed a second Marsh classification of biopsies (M0 to M3c) taken from the bulb and duodenum separately. Kappa (κ) scores between first and second evaluation determined the agreement. Plasma samples were collected at the day of intestinal biopsy and analysed for tissue transglutaminase autoantibodies (tTGA) using radioligand-binding assays. Results Marsh scores were concordant in 229/356 biopsies (64%, κ = 0.52, p < 0.0001). Among discordant results, 15/127 (12%) showed M0 in distal duodenum but ≥ M2 in the bulb, whereas the opposite was true for 8/127 (6%) of the biopsies. There were fewer collected duodenal biopsies, more missing bulb biopsies and missing CD3 staining among discordant evaluations. The second evaluation revealed a Marsh score compliant with coeliac disease in 22 children of whom seven children were tTGA positive. Conclusions The variation between university hospitals on the pathological evaluation of biopsies may lead to misdiagnosis of coeliac disease in paediatric patients. Access to clinical and endoscopic information as well as tTGA levels may be useful for the pathologist to complement the evaluation in dubious cases

Final analysis of a 14-year long-term follow-up study of the effectiveness and immunogenicity of the quadrivalent human papillomavirus vaccine in women from four nordic countries

Publisher's version (útgefin grein)Background: The quadrivalent human papillomavirus (qHPV) vaccine prevented vaccine HPV type-related infection and disease in young women in the 4-year FUTURE II efficacy study (NCT00092534). We report long-term effectiveness and immunogenicity at the end of 14 years of follow-up after enrollment in FUTURE II. Methods: Young women (16–23 years of age) from Denmark, Iceland, Norway, and Sweden who received three qHPV vaccine doses during the randomized, double-blind, placebo-controlled FUTURE II base study were followed for effectiveness for an additional ≥10 years through national registries. Tissue samples including but not limited to those collected during organized cervical cancer screening programs were obtained from regional biobanks to be adjudicated for histopathology diagnosis and tested for HPV DNA. The observed incidence of HPV16/18-related high-grade cervical dysplasia (primary outcome) was compared with recent historical background incidence rates in an unvaccinated population. Serum was collected at years 9 and 14 to assess antibody responses. Findings: No cases of HPV16/18-related high-grade cervical dysplasia were observed in the per-protocol effectiveness population (N = 2121; 24,099·0 person-years of follow-up) during the entire study. Vaccine effectiveness of 100% (95% CI 94·7–100) was demonstrated for ≥12 years, with a trend toward continued protection through 14 years post-vaccination. Seropositivity rates at study conclusion were >90% (HPV6/11/16) and 52% (HPV18) using competitive Luminex immunoassay, and >90% (all four HPV types) using the more sensitive IgG Luminex immunoassay. Interpretation: Vaccination of young women with qHPV vaccine offers durable protection against HPV16/18-related high-grade cervical dysplasia for ≥12 years, with a trend toward continued protection through 14 years post-vaccination, and induces sustained HPV6/11/16/18 antibody responses for up to 14 years post-vaccination. There was no evidence of waning immunity, suggesting no need for a booster dose during that period.Funding for this research was provided by Merck Sharp &Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ,USA (MSD).The authors would like to thank the study participants and base-study investigators. In particular, the authors are grateful to SuzanneCampbell, Ragnhild Flingtorp, and Bo Terning Hansen for contribu-tions to the study; Sara Nordqvist Kleppe for data management; andJette Junge for contributions serving on the pathology panel. Chris-tine Shields of MSD provided clinical scientist support to thefinalanalysis and contributed to the clinical study report. Roshonda Flor-ence of ExecuPharm provided operational leadership and coordi-nated with the pathology panel and central laboratories; this wasfunded by MSD.Medical writing support, under the direction of the authors, wasprovided by Erin Bekes, PhD, of CMC AFFINITY, McCann Health Medi-cal Communications, and was funded by MSD, in accordance withGood Publication Practice (GPP3) guidelines.Peer Reviewe

Spectrum of HPV types before and after treatment of cervical intraepithelial neoplasia grade 2 and 3

Background To monitor residual disease after treatment of high grade cervical intraepithelial neoplasia (CIN), cytology together with human papillomavirus (HPV) testing are commonly performed. Objectives To analyse the spectrum of HPV types before and after treatment. Study design This register-based study included 446 women treated for CIN2 or 3, where cytology samples had been HPV-tested before and after treatment by the use of the MGP-PCR Luminex HPV L1-DNA-assay identifying 39 HPV types, including 12 high risk (HR) HPV types. Results Before and after treatment, 706 and 248 HPV isolates were detected of 36 and 34 different HPV types, respectively. Among all the HR HPV isolates, type-specific persistency was observed among 14% (76/542) after treatment, compared to 34% (31/92) of low-risk (LR) HPV isolates (p < 0.001). Among the potential high risk (PHR) HPV isolates, 8.3% (6/72) persisted. Totally, 99% (440/446) and 40% (179/446) of the women were HPV-positive before and after treatment, respectively. At least one of the 12 HR HPV types was present in 91% (404/446) and 24% (109/446) of the women before and after treatment, respectively (p < 0.0001). HR HPV types were present both before and after treatment among 23% (102/446) of the women, and 16% (71/446) manifested at least one persistent HR HPV type. The sensitivity, specificity and negative predictive value of HR HPV testing for detection of residual high grade squamous intraepithelial lesion (HSIL) was based on the first cytology after treatment, and was 91.7% (95% CI: 61.5%–99.8%), 84.1% (95% CI: 80.0%–87.7%) and 99.7% (95% CI: 98.2%–100.0%), respectively. Conclusions About one out six treated women (16%) manifested at least one persistent HR HPV type, that was associated with recurrent or residual HSIL disease (odds ratio 58.1, 95% CI 7.4–457) (p = 0.0001). Testing for HR HPV demonstrated high sensitivity (92%) for residual HSIL. The higher persistency rate of LR HPV types suggests that they are more likely to be outside the treated area

Age influences the clinical significance of atypical glandular cells on cytology.

To evaluate women with atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) on cytology

Presence of High-Risk HPV mRNA in Relation to Future High-Grade Lesions among High-Risk HPV DNA Positive Women with Minor Cytological Abnormalities.

Continuous expression of E6- and E7-oncogenes of high-risk human papillomavirus (HPV) types is necessary for the development and maintenance of the dysplastic phenotype. The aim of the study was to determine the sensitivity and specificity of the APTIMA HPV mRNA assay (Hologic) in predicting future development of high-grade cervical intraepithelial neoplasia (CIN) among high-risk HPV-DNA-positive women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous epithelial lesion (LSIL) cytology

HPV types (DNA) detected in samples negative by the APTIMA HPV assay with a histologic diagnosis of CIN2.

<p>HPV types (DNA) detected in samples negative by the APTIMA HPV assay with a histologic diagnosis of CIN2.</p

Number of positive and negative APTIMA HPV mRNA test results, and outcome after up to 4.5 years of follow-up.

<p>Number of positive and negative APTIMA HPV mRNA test results, and outcome after up to 4.5 years of follow-up.</p