Estimation of the overall burden of cancers, precancerous lesions, and genital warts attributable to 9-valent HPV vaccine types in women and men in Europe

Background: In addition to cervical cancer, human papillomavirus (HPV) is responsible for a significant proportion of cancers and precancerous lesions of the vulva, vagina, anus, penis, head and neck, as well as genital warts. We estimated the annual number of new cases of these diseases attributable to 9-valent HPV vaccine types in women and men in Europe. Methods: The annual number of new cancers of the cervix, vulva, vagina, anus, penis, and selected head and neck sites in the population of the European Medicines Agency territory was estimated based on age-specific incidence rates extracted from Cancer Incidence in 5 Continents, Volume X and Eurostat population data for 2015. The annual number of new cancers attributable to 9-valent HPV vaccine types was estimated by applying the HPV attributable fraction from reference publications based on a large European multicenter study. For non-cervical cancers, HPV attributable fractions were based on oncogenically-active HPV infections only (i.e., detection of HPV DNA and either mRNA and/or p16 positivity). For precancerous lesions of the cervix, vulva, vagina, and anus, and for genital warts, previously published estimations were updated for the 2015 population. Results: The annual number of new cancers attributable to 9-valent HPV vaccine types was estimated at 47,992 (95% bound: 39,785-58,511). Cervical cancer showed the highest burden (31,130 cases), followed by head and neck cancer (6,786 cases), anal cancer (6,137 cases), vulvar cancer (1,466 cases), vaginal cancer (1,360 cases), and penile cancer (1,113 cases). About 81% were estimated to occur in women and 19% in men. The annual number of new precancerous lesions (CIN2+, VIN2/3, VaIN2/3, and AIN2/3) and genital warts attributable to 9-valent HPV vaccine types was estimated at 232,103 to 442,347 and 680,344 to 844,391, respectively. Conclusions: The burden of cancers associated with 9-valent HPV vaccine types in Europe is substantial in both sexes. Head and neck cancers constitute a heavy burden, particularly in men. Overall, about 90% of HPV-related cancers, 80% of precancerous lesions, and 90% of genital warts are expected to be attributable to 9-valent HPV vaccine types each year, demonstrating the important preventive potential of the 9-valent HPV vaccine in Europe

Potential impact of a nonavalent HPV vaccine on the occurrence of HPV-related diseases in France

International audienceBackground : Human Papillomavirus (HPV) infection is known to be associated with a number of conditions including cervical, vaginal, vulvar, penile, anal neoplasias and cancers, oropharynx cancers and genitals warts (GW). Two prophylactic vaccines are currently available: a bivalent vaccine designed to prevent HPV type 16 and 18 infection and a quadrivalent vaccine targeting HPV 6, 11, 16, and 18. In France, HPV vaccination is recommended in 11-14 year-old girls with a catch-up for girls aged 15-19. The objective of this study was to assess the potential impact of an HPV 6/11/16/18/31/33/45/52/58 nonavalent vaccine on anogenital and oropharyngeal HPV-related diseases in France.Methods : HPV genotype distributions from 6 multicentric retrospective studies (EDiTH I to VI) were analyzed including 516 cases of invasive cervical cancers (ICC), 493 high-grade cervical neoplasias (CIN2/3), 397 low-grade squamous intraepithelial lesions (LSIL), 423 GW, 366 anal cancer and 314 oropharyngeal carcinomas. Low and high estimates of HPV vaccine impact were calculated as follows: low estimate: prevalence of HPV 6/11/16/18/31/33/45/52/58 genotypes alone or in association but excluding presence of another HPV type; high estimate: prevalence of HPV 6/11/16/18/31/33/45/52/58 genotypes alone or in association, possibly in presence of another HPV type.Results : Estimates of potential impact varied from 85% (low estimate) to 92% (high estimate) for ICC, 77% to 90% for CIN2/3, 26% to 56% for LSIL, 69% to 90% for GW, 81% to 93% for anal cancer, and 41% to 44% for oropharyngeal carcinomas. Compared to the quadrivalent vaccine, the proportion of additional cases potentially prevented by the nonavalent vaccine was 9.9%-15.3% for ICC, 24.7%-33.3% for CIN2/3, 12.3%-22.7% for LSIL, 2.1%-5.4% for GW, 8.5%-10.4% for anal cancer, and 0.0%-1.6% for oropharyngeal carcinoma.Conclusions : The nonavalent HPV vaccine showed significant increased potential impact compared to the HPV 6/11/16/18 quadrivalent vaccine for ICC, CIN2/3 and LSIL. Considering a 100% vaccine efficacy and high vaccine coverage, about 90% of ICC, CIN2/3, GW or anal cancer cases could be prevented by a nonavalent HPV vaccine in France

Immortalized pathological human myoblasts: towards a universal tool for the study of neuromuscular disorders

<p>Abstract</p> <p>Background</p> <p>Investigations into both the pathophysiology and therapeutic targets in muscle dystrophies have been hampered by the limited proliferative capacity of human myoblasts. Isolation of reliable and stable immortalized cell lines from patient biopsies is a powerful tool for investigating pathological mechanisms, including those associated with muscle aging, and for developing innovative gene-based, cell-based or pharmacological biotherapies.</p> <p>Methods</p> <p>Using transduction with both telomerase-expressing and cyclin-dependent kinase 4-expressing vectors, we were able to generate a battery of immortalized human muscle stem-cell lines from patients with various neuromuscular disorders.</p> <p>Results</p> <p>The immortalized human cell lines from patients with Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, oculopharyngeal muscular dystrophy, congenital muscular dystrophy, and limb-girdle muscular dystrophy type 2B had greatly increased proliferative capacity, and maintained their potential to differentiate both <it>in vitro </it>and <it>in vivo </it>after transplantation into regenerating muscle of immunodeficient mice.</p> <p>Conclusions</p> <p>Dystrophic cellular models are required as a supplement to animal models to assess cellular mechanisms, such as signaling defects, or to perform high-throughput screening for therapeutic molecules. These investigations have been conducted for many years on cells derived from animals, and would greatly benefit from having human cell models with prolonged proliferative capacity. Furthermore, the possibility to assess <it>in vivo </it>the regenerative capacity of these cells extends their potential use. The innovative cellular tools derived from several different neuromuscular diseases as described in this report will allow investigation of the pathophysiology of these disorders and assessment of new therapeutic strategies.</p

Les dysfonctions faciales après parotidectomie conservatrice (Etude rétrospective à propos de 203 cas)

1) Objectif : Les dysfonctions du nerf facial après parotidectomie ont été étudiées rétrospectivement sur 203 cas, afin d'identifier leurs caractéristiques cliniques et les facteurs associés à leur survenue, et de proposer les moyens de leur prévention. 2) Matériels et méthodes : Cent trente et une parotidectomie conservatrices avec dissection derveuse pratiquées par le m^eme opérateur ont été incluses. La relation entre la survenue d'une dysfonction post-opératoire du nerf facail et différentes variables telles que le type de parotidectomie, les caractéristiques macroscopiques et histologiques des tumeurs, l'âge et le sexe du patient, a été analysée par un test du Chi-2. 3) Résultats : Une dysfonction faciale survient dans 42,2% des cas (35,1% de parésie, 5,3% de paralysie) en post-opératoire immédiat ; elle concerne un seul territoire nerveux dans 20,6% des cas, majoritairement la branche mandibulaire. Une atteinte persiste dans 30,7% des cas (22,9% de parésie, 7,6% de paralysie) 1 mois après l'intervention ; aucune n'est retrouvée au-delà de 6 mois, la durée moyenne étant de 3,18 mois. Les atteintes sont significativement plus fréquentes après parotidectomie subtotale (60,5%) qu'après parotidectomie superficielle (18,2%). Dans le groupe des parotidectomies subtotales (n=76), la survenue d'une dysfonction en post-opératoire immédiat comme à un mois est statistiquement liée à l'existence d'un contact du nerf avec la tumeur. Dans le groupe des parotidectomie superficelles (n=55), le taux de dysfonction est lié au type histologique de la tumeur ; à un mois post-opératoire, il est de 0% pour les tumeurs de Whartin, de 7,1% pour les tumeurs malignes, et de 31.2% pour les autres tumeurs bénignes...PARIS7-Villemin (751102101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

CHIRURGIE CONSERVATRICE DES CARCINOMES EPIDERMOIDES PHARYNGO-LARYNGES CLASSES T3-T4 (UNE ALTERNATIVE A LA RADIOTHERAPIE ET A LA LARYNGECTOMIE TOTALE CHEZ LES BONS REPONDEURS A LA CHIMIOTHERAPIE D'INDUCTION)

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Les sténoses laryngées et trachéales non-tumorales de l'adulte (à propos de 61 cas)

Les sténoses laryngées et trachéales, non tumorales de l'adulte, résultent d'un processus cicatriciel généré par la nécrose et l'effondrement de la charpente cartilagineuse et par l'ankylose des articulations trachéales. Elles sont le plus fréquemment d'origine iatrogène et consécutive aux techniques d'anesthésie et de réanimation. Leurs traitements sont multiples : médicaux, endoscopiques, et chirurgicaux par voie cervicale (résection anastomose ou agrandissement laryngé). Leur objectif vise à rétablir un diamètre laryngo-trachéal suffisant afin d'assurer la ventilation pulmonaire par les voies naturelles, en préservant au mieux la fonction vocale et les capacités de déglutition. La complexité des lésions et la tendance à la récidive imposent fréquemment l'utilisation successive de ces différents moyens thérapeutiques dans le temps. La mobilité aryténoïdienne, le degré d'inflammation au site de la sténose et la localisation précise de celle-ci, définie par les cartilages atteints, permettent de porter l'indication thérapeutique. L'examen clinique, la nasofibroscopie, l'endoscopie laryngo-trachéale sous anesthésie générale et le scanner cervico-thoracique sont indispensables à la réalisation du bilan pré-thérapeutique. Reprenant rétrospectivement une cohorte de 61 patients suivis avec un recul de 1 à 14 ans et confrontant nos résultats thérapeutiques à ceux publiés dans la littérature, nous proposons un axe décisionnel de traitement des sténoses laryngées et trachéales de l'adultePARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Les atteintes du nerf facial dans la chirurgie parotidienne

L atteinte faciale après parotidectomie est la complication post opératoire la plus redoutée du patient et du chirurgien. Dans la majorité des cas, la dysfonction faciale est incomplète et souvent partielle, et récupère dans l ensemble des cas dans les mois qui suivent le geste chirurgical. Les atteintes faciales sont associées à une morbidité significative et une modification esthétique apparente qui altèrent la qualité de vie de tous les jours. Plusieurs facteurs favorisants la survenue d une dysfonction faciale après parotidectomie ont été rapportés dans la littérature. Dans notre étude rétrospective sur les atteintes du nerf facial après 326 parotidectomies effectuées entre 2001 et 2009 sous monitorage du nerf facial, l étendue de la parotidectomie, le contact étroit entre le nerf facial et la tumeur, la localisation profonde de la tumeur et la chirurgie de reprise sont associées de façon significative à un risque élevé de dysfonction faciale post-opératoire. Ceci suggère que l étendue et la difficulté de la dissection nerveuse au cours de l intervention est le facteur favorisant essentiel des atteintes faciales. L évolution vers des techniques de parotidectomies moins invasives et la réduction de l étendue de résection du tissu parotidien dans le traitement des tumeurs bénignes de la parotide a permis de réduire la fréquence des atteintes faciales et des séquelles esthétiques post-opératoire, sans compromettre le contrôle tumorale et augmenter le risque de récidive.L utilisation du monitoring du nerf facial, malgré l absence de consensus à son sujet, reste un outil de sécurité complémentaire permettant un autocontrôle permanent complémentaire au contrôle visuel du nerf facial.Facial nerve dysfunction is the most feared postoperative complication after parotidectomy. In most cases, the facial nerve dysfunction is incomplete and partial; it recovers in the months following the surgery. Facial dysfunction is associated with a significant morbidity and a cosmetic modification that impair the patient s quality of life. Several factors predisposing the onset of facial dysfunction after parotidectomy have been reported in the literature. In our retrospective study on the facial nerve damages after 326 parotidectomies with continuous facial nerve monitoring between 2001 and 2009, only the extent of parotidectomy, the close contact between the facial nerve and the tumor, and revision surgery were significantly associated with a high risk of postoperative facial dysfunction. This suggests that the extent of parotidectomy and the difficult nerve dissection during the intervention is the key factor favorising the facial damage. The recent evolution toward less invasive operative techniques of parotidectomy and the lesser extent tissue resection in the treatment of parotid benign tumors has reduced the incidence of facial nerve injury and facial dysfunction after parotidectomy, without increasing the recurrence rate and compromising tumor control. The use facial nerve monitoring in parotid surgery, despite the lack of consensus on it, remains an additional security to visual facial observation.PARIS12-CRETEIL BU Médecine (940282101) / SudocSudocFranceF

Atrophy, Fibrosis, and Increased PAX7-Positive Cells in Pharyngeal Muscles of Oculopharyngeal Muscular Dystrophy Patients

ABSTRACT: Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant inherited dystrophy caused by an abnormal trinucleotide repeat expansion in the poly(A)-binding-protein-nuclear 1 (PABPN1) gene. Primary muscular targets of OPMD are the eyelid elevator and pharyngeal muscles, including the cricopharyngeal muscle (CPM), the progressive involution of which leads to ptosis and dysphagia, respectively. To understand the consequences of PABPN1 polyalanine expansion in OPMD, we studied muscle biopsies from 14 OPMD patients, 3 inclusion body myositis patients, and 9 healthy controls. In OPMD patient CPM (n = 6), there were typical dystrophic features with extensive endomysial fibrosis and marked atrophy of myosin heavy-chain IIa fibers. There were more PAX7-positive cells in all CPM versus other muscles (n = 5, control; n = 3, inclusion body myositis), and they were more numerous in OPMD CPM versus control normal CPM without any sign of muscle regeneration. Intranuclear inclusions were present in all OPMD muscles but unaffected OPMD patient muscles (i.e. sternocleidomastoid, quadriceps, or deltoid; n = 14) did not show evidence of fibrosis, atrophy, or increased PAX7-positive cell numbers. These results suggest that the specific involvement of CPM in OPMD might be caused by failure of the regenerative response with dysfunction of PAX7-positive cells and exacerbated fibrosis that does not correlate with the presence of PABPN1 inclusions