May Women with a Negative Co-Test at First Follow-Up Visit Return to 3-Year Screening after Treatment for Cervical Intraepithelial Neoplasia?

Background: The Norwegian Cervical Cancer Screening Programme recommends that women treated for cervical intraepithelial neoplasia (CIN) only be returned to 3-year screening after receiving two consecutive negative co-tests, 6 months apart. Here we evaluate adherence to these guidelines and assessed the residual disease, using CIN3+ as the outcome. Methods: This cross-sectional study comprised 1397 women, treated for CIN between 2014 and 2017, who had their cytology, HPV, and histology samples analyzed by a single university department of pathology. Women who had their first and second follow-up at 4–8 and 9–18 months after treatment were considered adherent to the guidelines. The follow-up ended on 31 December 2021. We used survival analysis to assess the residual and recurrent CIN3 or worse among women with one and two negative co-tests, respectively. Results: 71.8% (1003/1397) of women attended the first follow-up 4–8 months after treatment, and 38.3% were considered adherent at the second follow-up. Nearly 30% of the women had incomplete follow-up at the study end. None of the 808 women who returned to 3-year screening after two negative co-tests were diagnosed with CIN3+, whereas two such cases were diagnosed among the 887 women who had normal cytology/ASCUS/LSIL and a negative HPV test at first follow-up (5-year risk of CIN3+: 0.24, 95%, CI: 0.00–0.57 per 100 woman-years). Conclusions: The high proportion of women with incomplete follow-up at the end of the study period requires action. The risk of CIN3+ among women with normal cytology/ASCUS/LSIL and a negative HPV test at first follow-up is indicative of a return to 3-year screening

Population-based screening for celiac disease reveals that the majority of patients are undiagnosed and improve on a gluten-free diet

The impact of a gluten-free diet (GFD) on screen-detected celiac disease (CD) is currently ambiguous. We aimed to identify the population-based prevalence of undiagnosed adult CD and examine the impact of a GFD on screen-detected CD. In total, 12,981 adults participated in a population-based health study in Tromsø, Norway. Participants with increased levels of anti-tissue transglutaminase-2 IgA or anti-deamidated gliadin peptide IgG were invited to undergo gastroduodenoscopy with both histological and immunohistochemical examination of small-bowel biopsies. The prevalence of previously diagnosed CD was 0.37%. Additionally, the prevalence of previously undiagnosed CD was 1.10%. Thus, 1.47% of the population had CD, of whom 75% were previously undiagnosed. A GFD resulted in signifcant improvements in overall gastrointestinal symptoms, diarrhea, and healthrelated quality of life, with reduced abdominal discomfort (76%) and improved levels of energy (58%). The large majority of patients with adult CD were undiagnosed and benefted from a GFD with reduced gastrointestinal symptoms and improved health-related quality of life. In clinical practice, there should be a low threshold for CD testing even in the absence of abdominal complaints because most adult patients appear to consider their symptoms a part of their normal state and therefore remain untested and undiagnosed

Triage of Women with Low-Grade Cervical Lesions - HPV mRNA Testing versus Repeat Cytology

BACKGROUND: In Norway, women with low-grade squamous intraepithelial lesions (LSIL) are followed up after six months in order to decide whether they should undergo further follow-up or be referred back to the screening interval of three years. A high specificity and positive predictive value (PPV) of the triage test is important to avoid unnecessary diagnostic and therapeutic procedures. MATERIALS AND METHODS: At the University Hospital of North Norway, repeat cytology and the HPV mRNA test PreTect HPV-Proofer, detecting E6/E7 mRNA from HPV types 16, 18, 31, 33 and 45, are used in triage of women with ASC-US and LSIL. In this study, women with LSIL cytology in the period 2005-2008 were included (n = 522). Two triage methods were evaluated in two separate groups: repeat cytology only (n = 225) and HPV mRNA testing in addition to repeat cytology (n = 297). Histologically confirmed cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) was used as the study endpoint. RESULTS: Of 522 women with LSIL, 207 had biopsies and 125 of them had CIN2+. The sensitivity and specificity of repeat cytology (ASC-US or worse) were 85.7% (95% confidence interval (CI): 72.1, 92.2) and 54.4 % (95% CI: 46.9, 61.9), respectively. The sensitivity and specificity of the HPV mRNA test were 94.2% (95% CI: 88.7, 99.7) and 86.0% (95% CI: 81.5, 90.5), respectively. The PPV of repeat cytology was 38.4% (95% CI: 29.9, 46.9) compared to 67.0% (95% CI: 57.7, 76.4) of the HPV mRNA test. CONCLUSION: HPV mRNA testing was more sensitive and specific than repeat cytology in triage of women with LSIL cytology. In addition, the HPV mRNA test showed higher PPV. These data indicate that the HPV mRNA test is a better triage test for women with LSIL than repeat cytology

13-Type HPV DNA Test versus 5-Type HPV mRNA Test in Triage of Women Aged 25–33 Years with Minor Cytological Abnormalities–6 Years of Follow-Up

Background: A specific, cost-effective triage test for minor cytological abnormalities is essential for cervical cancer screening among younger women to reduce overmanagement and unnecessary healthcare utilization. We compared the triage performance of one 13-type human papillomavirus (HPV) DNA test and one 5-type HPV mRNA test. Methods: We included 4115 women aged 25–33 years with a screening result of atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL) recorded in the Norwegian Cancer Registry during 2005–2010. According to Norwegian guidelines, these women went to triage (HPV testing and repeat cytology: 2556 were tested with the Hybrid Capture 2 HPV DNA test, which detects the HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68; and 1559 were tested with the PreTect HPV-Proofer HPV mRNA test, which detects HPV types 16, 18, 31, 33, and 45). Women were followed through December 2013. Results: HPV positivity rates at triage were 52.8% and 23.3% among DNAand mRNA-tested women (p < 0.001), respectively. Referral rates for colposcopy and biopsy and repeat testing (HPV + cytology) after triage were significantly higher among DNA-tested (24.9% and 27.9%) compared to mRNA-tested women (18.3% and 5.1%), as were cervical intraepithelial neoplasia grade 3 or worse (CIN3+) detection rates (13.1% vs. 8.3%; p < 0.001). Ten cancer cases were diagnosed during follow-up; eight were in DNA-tested women. Conclusion: We observed significantly higher referral rates and CIN3+ detection rates in young women with ASC-US/LSIL when the HPV DNA test was used at triage. The mRNA test was as functional in cancer prevention, with considerably less healthcare utilization

HPV E6/E7 mRNA Testing Is More Specific than Cytology in Post-Colposcopy Follow-Up of Women with Negative Cervical Biopsy

BACKGROUND: In Norway, women with negative or low-grade cervical biopsies (normal/CIN1) are followed up after six months in order to decide on further follow-up or recall for screening at three-year intervals. A high specificity and positive predictive value (PPV) of the triage test is important to avoid unnecessary diagnostic and therapeutic procedures whereas a low risk of high-grade disease among triage negative women assures safety. MATERIALS AND METHODS: At the University Hospital of North Norway, cytology and the HPV mRNA test PreTect HPV-Proofer, detecting E6/E7 mRNA from HPV types 16, 18, 31, 33 and 45, are used in post-colposcopy follow-up of women with negative or low-grade biopsy. In this study, women with negative biopsy after high grade cytology (ASC-H/HSIL) and/or positive HPV mRNA test in the period 2005-2009 were included (n = 520). Histologically confirmed cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) was used as study endpoint. RESULTS: Of 520 women with negative or low-grade biopsy, 124 women (23.8%) had CIN2+ in follow-up biopsy. The sensitivity and specificity of the HPV mRNA test were 89.1% (95% CI, 80.1-98.1) and 92.5% (95% CI, 88.2-96.7), respectively. The ratios of sensitivity, specificity and PPV of HPV mRNA testing compared to repeat cytology for finding CIN2+ was 1.05 (95% CI: 0.92-1.21), 1.21 (95% CI: 1.12-1.32), and 1.49 (95% CI: 1.20-1.86), respectively. The PPV of mRNA was 77.3% (95% CI, 59.8-94.8) in women aged 40 or older. CONCLUSION: Women with negative cervical biopsy require follow-up before resumption of routine screening. Post-colposcopy HPV mRNA testing was as sensitive but more specific than post-colposcopy cytology. In addition, the HPV mRNA test showed higher PPV. A positive mRNA test post-colposcopy could justify treatment in women above 40 years

Redegjør for HPV-resultater

Fire Tromsø-leger tilbakeviser kritikk fra Bergen-professor om at de har oversolgt resultater fra sin studie om HPV-testing. De redegjør for hvordan de har fulgt opp kvinner med usikre celleforandringer

Prediction of long-term remission in patients following discontinuation of anti-TNF therapy in ulcerative colitis: a 10 year follow up study

Background - The long-term outcomes of Ulcerative colitis (UC) after discontinuation of biological therapy are largely unknown. There is also a lack of accurate and validated markers that can predict outcome after withdrawal accurately. The aims of this study were to describe the long-term outcomes in UC patients following cessation of anti-TNF therapy and explore potential biomarkers as an approach towards precision medicine. Methods - Seventy-five patients with moderate to severe UC treated to remission with anti-tumor necrosis factor (TNF) were included in the study. This is a follow-up of previously reported UC outcomes. The patients were categorized as either “Remission” or “Relapse”. The “Relapse” group was divided into subgroups determined by the highest treatment level needed to obtain remission the last 3 years of observation: non-biological therapy, biological therapy or colectomy. Remission were divided in long term remission (LTR), those using immunomodulating drugs (LTR + imids) and those using only 5-amino-salicylate (5-ASA) treatment (LTR) for the past 3 years. Analyses of mucosal gene expression by real-time PCR were performed. Results - The median (IQR) observation time of all patients included was 121 (111–137) months. Of the 75 patients, 46 (61%) did not receive biological therapy, including 23 (31%) in LTR ± imids. Of these 23 patients, 16 (21%) were defined as LTR with a median observation time of (IQR) 95 (77–113) months. In total 14 patients (19%) underwent colectomy during the 10 years after first remission. Mucosal TNF copies/µg mRNA  Conclusion - In this 10-year follow-up of UC of patients with moderate to severe disease, 61% of patients experience an altered phenotype to a milder disease course without need of biological therapy. Twenty-one percent of the patients were LTR without any medication except of 5-ASA. Mucosal TNF gene expression and IL1RL1- transcripts may be of clinical utility for long term prognosis in development of precision medicine in UC

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

Støtter dansk HPV-praksis

Danskene har en fornuftig praksis når kvinner med lette celleforandringer blir undersøkt med en spesifikk HPV mRNA test i stedet for umiddelbar kolposkopi og biopsi