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

Causes of higher symptomatic airway load in patients with chronic rhinosinusitis

Background Chronic rhinosinusitis display a variety of different phenotypes. The symptoms of disease are characterised by various signs and symptoms such as nasal congestion, nasal discharge, pressure sensation in the face and reduced or complete loss of smell. In a patient population undergoing functional endoscopic sinonasal surgery (FESS) for chronic rhinosinusitis, we wanted to investigate the clinical features and explore if the presence of biofilm, nasal polyps or other disease characteristic could serve as predictor for the symptomatic load. A patient group undergoing septoplasty without disease of the sinuses was included as control. Methods The Sinonasal outcome test (SNOT-20), EPOS visual analogue scale (VAS) and the Lund-Mackey CT score (LM CT score) were used to examine 23 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), 30 patient with nasal polyps (CRSwNP) and 22 patients with septal deviation. Tissue samples were collected prospectively during surgery. The cohort has previously been examined for the presence of biofilm. Results Patients with CRSsNP and CRSwNP had significantly higher degree of symptoms compared to the septoplasty group (SNOT-20 scores of 39.8, 43.6 and 29.9, respectively, p = 0.034). There were no significant differences in the total SNOT-20 or VAS symptoms scores between the CRSsNP and CRSwNP subgroups. However patients with nasal polyps showed significantly higher scores of symptoms related to sinonasal discomfort such as cough, runny nose and need to blow nose (p = 0.011, p = 0.046, p = 0.001 respectively). Patients with nasal polyps showed a significantly higher LM CT score compared to patients without polyps (12.06 versus 8.00, p = 0.001). The presence of biofilm did not impact the degree of symptoms. Conclusion The presence of nasal polyp formations in CRS patients was associated with a higher symptomatic airway load as compared to patients without polyps. These findings suggest that nasal polyps could be an indicator of more substantial sinonasal disease. The presence of biofilm did not impact the degree of symptoms, however, as biofilm seem to be a common feature of chronic rhinosinusitis (89% in this cohort), it is more likely to be involved in the development of the CRS, rather than being a surrogate marker for increased symptomatic load

Improved Survival after Implementation of Multidisciplinary Team Meetings, Perioperative Chemotherapy, Extended Lymphnode Dissection and Laparoscopic Surgery in the Treatment of Advances Gastric Cancer

Aims: The treatment of gastric cancer has changed in the western countries during the last decade. This includes multidisciplinary team (MDT) meetings, perioperative chemotherapy, extended lymph node dissection, and laparoscopic surgery, all of which were gradually implemented at our department from 2008. The aim of the present study was to determine the effect of these changes on morbidity and survival. Material and Methods: 185 patients with gastric cancer were operated with curative intent from 2000 until 2016 in this retrospective, observational, follow-up study; 83 before implementation of modern principles in 2008 (period 1) and 102 were treated after 2008 (period 2). Results: The resection rate (94% vs 92.8%) and mortality rates (4.8% vs 2.9%) did not differ between the two periods. In period 2, 48 patients (47.1%), received neoadjuvant chemotherapy. In 36 patients (35.3%), laparoscopic surgery with D2 lymphadenectomy was performed. There was a significantly higher yield in the number of lymph nodes in period 2 compared to period 1 (14 vs 8, p < 0.001). This is also apparent between laparoscopic and open surgery in the second period (32 vs 10, p < 0.001). The five-year survival rate was significantly improved after the change in treatment principles with an estimated improvement from 30% to 40% between the periods (p = 0.033). Conclusion: The combined effect of MDT meetings, neoadjuvant chemotherapy, extended lymphnode dissection and laparoscopy has improved the prognosis of gastric cancer patients. KEYWORDS Gastric Cancer, Chemotherapy, Laparoscopy, Survival, D2 Lymphadenectom

Long-term effectiveness of the nine-valent human papillomavirus vaccine in Scandinavian women:interim analysis after 8 years of follow-up

A long-term follow-up (LTFU) of the nine-valent human papillomavirus (9vHPV) vaccine efficacy study in young women aged 16–26 years was initiated to evaluate if vaccine effectiveness for up to 14 years post-vaccination will remain above 90%. Vaccine effectiveness is measured as percent reduction in the incidence of HPV16/18/31/33/45/52/58-related high-grade cervical dysplasia in the LTFU cohort relative to expected incidence in a similar unvaccinated cohort. We report an interim analysis 8 years post-vaccination. Overall, 2029 participants from Denmark, Norway, and Sweden who received the 9vHPV vaccine during the clinical efficacy study continued into the LTFU study. National health registries were used to identify screening attendance and cervical pre-cancer/cancer diagnoses. Tissue samples were retrieved for HPV testing by PCR and pathology diagnosis adjudication. A control chart method was used to detect signals indicative of vaccine effectiveness waning below 90%. No new cases of HPV16/18/31/33/45/52/58-related high-grade cervical dysplasia were observed during the LTFU study period over 4084.2 person-years’ follow-up (per-protocol effectiveness population; n = 1448). Thus, there were no signals indicative of vaccine effectiveness waning below 90%. These observations show that the 9vHPV vaccine provides continued statistically significant protection through at least 6 years, with indications of continued effectiveness through 8 years. Trial registration Clinicaltrials.gov: NCT00543543, NCT02653118

Additional file 1: of Causes of higher symptomatic airway load in patients with chronic rhinosinusitis

Data containing patient disease classification, allergy status, asthma status, LM CT score, VAS score, SNOT score and biofilm status. (XLS 28 kb

The impact of radiotherapy in the treatment of desmoid tumours. An international survey of 110 patients. A study of the Rare Cancer Network

Abstract Purpose A multi-centre study to assess the value of combined surgical resection and radiotherapy for the treatment of desmoid tumours. Patients and methods One hundred and ten patients from several European countries qualified for this study. Pathology slides of all patients were reviewed by an independent pathologist. Sixty-eight patients received post-operative radiotherapy and 42 surgery only. Median follow-up was 6 years (1 to 44). The progression-free survival time (PFS) and prognostic factors were analysed. Results The combined treatment with radiotherapy showed a significantly longer progression-free survival than surgical resection alone (p smaller than 0.001). Extremities could be preserved in all patients treated with combined surgery and radiotherapy for tumours located in the limb, whereas amputation was necessary for 23% of patients treated with surgery alone. A comparison of PFS for tumour locations proved the abdominal wall to be a positive prognostic factor and a localization in the extremities to be a negative prognostic factor. Additional irradiation, a fraction size larger than or equal to 2 Gy and a total dose larger than 50 Gy to the tumour were found to be positive prognostic factors with a significantly lower risk for a recurrence in the univariate analysis. This analysis revealed radiotherapy at recurrence as a significantly worse prognostic factor compared with adjuvant radiotherapy. The addition of radiotherapy to the treatment concept was a positive prognostic factor in the multivariate analysis. Conclusion Postoperative radiotherapy significantly improved the PFS compared to surgery alone. Therefore it should always be considered after a non-radical tumour resection and should be given preferably in an adjuvant setting. It is effective in limb preservation and for preserving the function of joints in situations where surgery alone would result in deficits, which is especially important in young patients.</p