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      Identification of HPV Types and Mycobacterium Tuberculosis Complex in Historical Long-Term Preserved Formalin Fixed Tissues in Different Human Organs

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          Abstract

          University anatomical-pathological collections represent huge sources of human tissues and preparations from a variety of different diseases. With the help of modern genetic and histological methods, preserved fixed tissues from pathological collections can be used to re-evaluate former diagnoses. We analysed 25 specimens from our pathological collection with ages ranging from 78 to 112 years. The tissues originated from the oral cavity, lip, tongue, lung, bone, kidney, spleen, thymus, larynx, lymph node, penis and uterine cervix with an original diagnosis of epithelial cancers or tuberculosis. Amplifiable DNA was extracted and in epithelial cancers, potential HPV infection was investigated. Specimens with an original diagnosis of tuberculosis were examined for mycobacterial infection. The tissues were also examined using modern histological methods. Our data showed that in 24/25 specimens the histological structure was preserved and in 10/11 specimens the diagnosis of squamous cell carcinoma could be confirmed. Additionally, HPV type 16 was detected in 8 specimens. The histological pattern of tuberculosis was found in 11/14 specimens and the Mycobacterium tuberculosis complex was ascertained in four specimens. Our study showed that pathogens such as HPV or Mycobacterium tuberculosis can be detected in historical pathological preparations, and that these collections are suitable for further epidemiological research.

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          Most cited references23

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          Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States.

          To investigate the impact of human papillomavirus (HPV) on the epidemiology of oral squamous cell carcinomas (OSCCs) in the United States, we assessed differences in patient characteristics, incidence, and survival between potentially HPV-related and HPV-unrelated OSCC sites. Data from nine Surveillance, Epidemiology, and End Results program registries (1973 to 2004) were used to classify OSCCs by anatomic site as potentially HPV-related (n = 17,625) or HPV-unrelated (n = 28,144). Joinpoint regression and age-period-cohort models were used to assess incidence trends. Life-table analyses were used to compare 2-year overall survival for HPV-related and HPV-unrelated OSCCs. HPV-related OSCCs were diagnosed at younger ages than HPV-unrelated OSCCs (mean ages at diagnosis, 61.0 and 63.8 years, respectively; P < .001). Incidence increased significantly for HPV-related OSCC from 1973 to 2004 (annual percentage change [APC] = 0.80; P < .001), particularly among white men and at younger ages. By contrast, incidence for HPV-unrelated OSCC was stable through 1982 (APC = 0.82; P = .186) and declined significantly during 1983 to 2004 (APC = -1.85; P < .001). When treated with radiation, improvements in 2-year survival across calendar periods were more pronounced for HPV-related OSCCs (absolute increase in survival from 1973 through 1982 to 1993 through 2004 for localized, regional, and distant stages = 9.9%, 23.1%, and 18.6%, respectively) than HPV-unrelated OSCCs (5.6%, 3.1%, and 9.9%, respectively). During 1993 to 2004, for all stages treated with radiation, patients with HPV-related OSCCs had significantly higher survival rates than those with HPV-unrelated OSCCs. The proportion of OSCCs that are potentially HPV-related increased in the United States from 1973 to 2004, perhaps as a result of changing sexual behaviors. Recent improvements in survival with radiotherapy may be due in part to a shift in the etiology of OSCCs.
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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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              Restricted structural gene polymorphism in the Mycobacterium tuberculosis complex indicates evolutionarily recent global dissemination.

              One-third of humans are infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. Sequence analysis of two megabases in 26 structural genes or loci in strains recovered globally discovered a striking reduction of silent nucleotide substitutions compared with other human bacterial pathogens. The lack of neutral mutations in structural genes indicates that M. tuberculosis is evolutionarily young and has recently spread globally. Species diversity is largely caused by rapidly evolving insertion sequences, which means that mobile element movement is a fundamental process generating genomic variation in this pathogen. Three genetic groups of M. tuberculosis were identified based on two polymorphisms that occur at high frequency in the genes encoding catalase-peroxidase and the A subunit of gyrase. Group 1 organisms are evolutionarily old and allied with M. bovis, the cause of bovine tuberculosis. A subset of several distinct insertion sequence IS6110 subtypes of this genetic group have IS6110 integrated at the identical chromosomal insertion site, located between dnaA and dnaN in the region containing the origin of replication. Remarkably, study of approximately 6,000 isolates from patients in Houston and the New York City area discovered that 47 of 48 relatively large case clusters were caused by genotypic group 1 and 2 but not group 3 organisms. The observation that the newly emergent group 3 organisms are associated with sporadic rather than clustered cases suggests that the pathogen is evolving toward a state of reduced transmissability or virulence.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                23 January 2017
                2017
                : 12
                : 1
                : e0170353
                Affiliations
                [001]Institute of Pathology, University Medicine of Rostock, Rostock, Germany
                Hebrew University, ISRAEL
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: MH AE AO PR.

                • Formal analysis: MH PR.

                • Investigation: MH PR.

                • Methodology: MH AE PR.

                • Project administration: MH AE PR.

                • Validation: MH PR.

                • Visualization: MH PR.

                • Writing – original draft: MH AE PR.

                • Writing – review & editing: MH AE PR.

                Article
                PONE-D-16-38431
                10.1371/journal.pone.0170353
                5256871
                28114406
                17f3c255-247c-4655-94c5-1559dd4edcd2
                © 2017 Hühns et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 26 September 2016
                : 3 January 2017
                Page count
                Figures: 3, Tables: 5, Pages: 14
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Biology and Life Sciences
                Organisms
                Bacteria
                Actinobacteria
                Mycobacterium Tuberculosis
                Biology and Life Sciences
                Anatomy
                Histology
                Medicine and Health Sciences
                Anatomy
                Histology
                Biology and Life Sciences
                Molecular Biology
                Molecular Biology Techniques
                Artificial Gene Amplification and Extension
                Polymerase Chain Reaction
                Research and Analysis Methods
                Molecular Biology Techniques
                Artificial Gene Amplification and Extension
                Polymerase Chain Reaction
                Medicine and Health Sciences
                Urology
                Genitourinary Infections
                Human Papillomavirus Infection
                Medicine and Health Sciences
                Infectious Diseases
                Sexually Transmitted Diseases
                Human Papillomavirus Infection
                Medicine and Health Sciences
                Infectious Diseases
                Viral Diseases
                Human Papillomavirus Infection
                Medicine and Health Sciences
                Infectious Diseases
                Bacterial Diseases
                Tuberculosis
                Medicine and Health Sciences
                Tropical Diseases
                Tuberculosis
                Medicine and Health Sciences
                Diagnostic Medicine
                Cancer Detection and Diagnosis
                Medicine and Health Sciences
                Oncology
                Cancer Detection and Diagnosis
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Carcinomas
                Medicine and Health Sciences
                Infectious Diseases
                Bacterial Diseases
                Tuberculosis
                Miliary Tuberculosis
                Medicine and Health Sciences
                Tropical Diseases
                Tuberculosis
                Miliary Tuberculosis
                Custom metadata
                All relevant data are within the paper.

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                Uncategorized

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