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      Recurrent respiratory papillomatosis: an overview of current thinking and treatment

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          Abstract

          Human papillomaviruses (HPV) infection in benign laryngeal papillomas is well established. The vast majority of recurrent respiratory papillomatosis lesions are due to HPV types 6 and 11. Human papillomaviruses are small non-enveloped viruses (>8 kb), that replicate within the nuclei of infected host cells. Infected host basal cell keratinocytes and papillomas arise from the disordered proliferation of these differentiating keratinocytes. Surgical debulking of papillomas is currently the treatment of choice; newer surgical approaches utilizing microdebriders are replacing laser ablation. Surgery aims to secure an adequate airway and improve and maintain an acceptable quality of voice. Adjuvant treatments currently used include cidofovir, indole-3-carbinol, ribavirin, mumps vaccine, and photodynamic therapy. The recent licensing of prophylactic HPV vaccines is a most interesting development. The low incidence of RRP does pose significant problems in recruitment of sufficient numbers to show statistical significance. Large multi-centre collaborative clinical trials are therefore required. Even so, sufficient clinical follow-up data would take several years.

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          Most cited references47

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          Human Papillomavirus Types in Head and Neck Squamous Cell Carcinomas Worldwide: A Systematic Review

          A. Kreimer (2005)
          Mucosal human papillomaviruses (HPV) are the cause of cervical cancer and likely a subset of head and neck squamous cell carcinomas (HNSCC), yet the global prevalence and type distribution of HPV in HNSCC remains unclear. We systematically reviewed published studies of HNSCC biopsies that employed PCR-based methods to detect and genotype HPV to describe the prevalence and type distribution of HPV by anatomic cancer site. Geographic location and study size were investigated as possible sources of variability. In the 5,046 HNSCC cancer specimens from 60 studies, the overall HPV prevalence was 25.9% [95% confidence interval (95% CI), 24.7-27.2]. HPV prevalence was significantly higher in oropharyngeal SCCs (35.6% of 969; 95% CI, 32.6-38.7) than oral SCCs (23.5% of 2,642; 95% CI, 21.9-25.1) or laryngeal SCCs (24.0% of 1,435; 95% CI, 21.8-26.3). HPV16 accounted for a larger majority of HPV-positive oropharyngeal SCCs (86.7%; 95% CI, 82.6-90.1) compared with HPV-positive oral SCCs (68.2%; 95% CI, 64.4-71.9) and laryngeal SCCs (69.2%; 95% CI, 64.0-74.0). Conversely, HPV18 was rare in HPV-positive oropharyngeal SCCs (2.8%; 95% CI, 1.3-5.3) compared with other head and neck sites [34.1% (95% CI, 30.4-38.0) of oral SCCs and 17.0% (95% CI, 13.0-21.6) of laryngeal SCCs]. Aside from HPV16 and HPV18, other oncogenic HPVs were rarely detected in HNSCC. Tumor site-specific HPV prevalence was higher among studies from North America compared with Europe and Asia. The high HPV16 prevalence and the lack of HPV18 in oropharyngeal compared with other HNSCCs may point to specific virus-tissue interactions. Small sample size and publication bias complicate the assessment of the prevalence of HPV in head and neck sites beyond the oropharynx.
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            Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group.

            Epidemiologic studies have shown that the association of genital human papillomavirus (HPV) with cervical cancer is strong, independent of other risk factors, and consistent in several countries. There are more than 20 different cancer-associated HPV types, but little is known about their geographic variation. Our aim was to determine whether the association between HPV infection and cervical cancer is consistent worldwide and to investigate geographic variation in the distribution of HPV types. More than 1000 specimens from sequential patients with invasive cervical cancer were collected and stored frozen at 32 hospitals in 22 countries. Slides from all patients were submitted for central histologic review to confirm the diagnosis and to assess histologic characteristics. We used polymerase chain reaction-based assays capable of detecting more than 25 different HPV types. A generalized linear Poisson model was fitted to the data on viral type and geographic region to assess geographic heterogeneity. HPV DNA was detected in 93% of the tumors, with no significant variation in HPV positivity among countries. HPV 16 was present in 50% of the specimens, HPV 18 in 14%, HPV 45 in 8%, and HPV 31 in 5%. HPV 16 was the predominant type in all countries except Indonesia, where HPV 18 was more common. There was significant geographic variation in the prevalence of some less common virus types. A clustering of HPV 45 was apparent in western Africa, while HPV 39 and HPV 59 were almost entirely confined to Central and South America. In squamous cell tumors, HPV 16 predominated (51% of such specimens), but HPV 18 predominated in adenocarcinomas (56% of such tumors) and adenosquamous tumors (39% of such tumors). Our results confirm the role of genital HPVs, which are transmitted sexually, as the central etiologic factor in cervical cancer worldwide. They also suggest that most genital HPVs are associated with cancer, at least occasionally. The demonstration that more than 20 different genital HPV types are associated with cervical cancer has important implications for cervical cancer-prevention strategies that include the development of vaccines targeted to genital HPVs.
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              Association of human papillomavirus types 16 and 18 E6 proteins with p53.

              Human papillomavirus type 16 (HPV-16) is a DNA tumor virus that is associated with human anogenital cancers and encodes two transforming proteins, E6 and E7. The E7 protein has been shown to bind to the retinoblastoma tumor suppressor gene product, pRB. This study shows that the E6 protein of HPV-16 is capable of binding to the cellular p53 protein. The ability of the E6 proteins from different human papillomaviruses to form complexes with p53 was assayed and found to correlate with the in vivo clinical behavior and the in vitro transforming activity of these different papillomaviruses. The wild-type p53 protein has tumor suppressor properties and has also been found in association with large T antigen and the E1B 55-kilodalton protein in cells transformed by SV40 and by adenovirus type 5, respectively, providing further evidence that the human papillomaviruses, the adenoviruses, and SV40 may effect similar cellular pathways in transformation.
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                Author and article information

                Contributors
                +44-1223-245151 , +44-1223-217559 , holger.sudhoff@rub.de
                Journal
                Eur Arch Otorhinolaryngol
                European Archives of Oto-Rhino-Laryngology
                Springer-Verlag (Berlin/Heidelberg )
                0937-4477
                1434-4726
                29 November 2007
                February 2008
                : 265
                : 2
                : 147-151
                Affiliations
                [1 ]Department of Genito-urinary Medicine, Addenbrooke’s Hospital, Cambridge, UK
                [2 ]Department of Pathology, University of Cambridge, Cambridge, UK
                [3 ]Department of Otolaryngology and Skull Base Surgery, Addenbrooke’s Hospital, Cambridge, UK
                Article
                546
                10.1007/s00405-007-0546-z
                2217621
                18046565
                63cd4575-5304-4fdd-9a36-37dc5fc2228d
                © Springer-Verlag 2007
                History
                : 3 March 2007
                : 16 November 2007
                Categories
                Review Article
                Custom metadata
                © Springer-Verlag 2008

                Otolaryngology
                vaccination,human papilloma virus,hpv 6 and 11,recurrent respiratory papillomatosis

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