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      Comparison of PapilloCheck and linear array to detect and differentiate human papillomaviruses in cervical and tonsillar smears from females with cervical intraepithelial lesions

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          Abstract

          A subgroup of oropharyngeal squamous cell carcinomas (OSCCs) are causally linked to infection with high-risk human papillomaviruses (HR-HPVs). To evaluate the prevalence of simultaneous oral HPV infection in females with cervical high-grade squamous intraepithelial lesions (HSIL), tonsillar- and cervical smears were collected simultaneously from 73 patients and analyzed for HPV using two commercial assays, PapilloCheck (Greiner-Bio-One) and Linear Array (Roche). Only 3/73 (4.1%) tonsillar smears were HPV positive (HPV+), with HPV types 16, 35, and 45, respectively, detected by both assays (100% agreement). Concordant results were also found in 60/66 (91%) evaluable cervical smears. Of specimens, positive by both assays, typing results completely coincide in 71% (all types are identical) and partially coincide in 27% (at least one type is identical). Taken together, results of HPV detection and typing by PapilloCheck and Linear Array are highly congruent and confirm the low prevalence of HR-HPV in tonsillar smears of patients with HSIL of the uterine cervix. Our data indicate low prevalence of oropharyngeal HPV infection in patients with high-grade cervical dysplasia. The low detection rate was confirmed by using two different commercial assays with largely consistent results of HPV detection and typing, but with some variation for particular HPV types. Comparative testing of larger numbers is required to identify the HPV types prone to escape detection with particular assays.

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          Human papillomavirus and cervical cancer.

          Cervical cancer is the second most common cancer in women worldwide, and knowledge regarding its cause and pathogenesis is expanding rapidly. Persistent infection with one of about 15 genotypes of carcinogenic human papillomavirus (HPV) causes almost all cases. There are four major steps in cervical cancer development: infection of metaplastic epithelium at the cervical transformation zone, viral persistence, progression of persistently infected epithelium to cervical precancer, and invasion through the basement membrane of the epithelium. Infection is extremely common in young women in their first decade of sexual activity. Persistent infections and precancer are established, typically within 5-10 years, from less than 10% of new infections. Invasive cancer arises over many years, even decades, in a minority of women with precancer, with a peak or plateau in risk at about 35-55 years of age. Each genotype of HPV acts as an independent infection, with differing carcinogenic risks linked to evolutionary species. Our understanding has led to improved prevention and clinical management strategies, including improved screening tests and vaccines. The new HPV-oriented model of cervical carcinogenesis should gradually replace older morphological models based only on cytology and histology. If applied wisely, HPV-related technology can minimise the incidence of cervical cancer, and the morbidity and mortality it causes, even in low-resource settings.
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            Improved amplification of genital human papillomaviruses.

            Genital human papillomaviruses (HPVs) are commonly detected from clinical samples by consensus PCR methods. Two commonly used primer systems, the MY09-MY11 (MY09/11) primers and the GP5+-GP6+ (GP5+/6+) primers, amplify a broad spectrum of HPV genotypes, but with various levels of sensitivity among the HPV types. Analysis of the primer-target sequence homology for the MY09/11 primers showed an association between inefficient amplification of HPV types and the number and position of mismatches, despite accommodation of sequence variation by inclusion of degenerate base sites. The MY09/11 primers were redesigned to increase the sensitivity of amplification across the type spectrum by using the same primer binding regions in the L1 open reading frame. Sequence heterogeneity was accommodated by designing multiple primer sequences that were combined into an upstream pool of 5 oligonucleotides (PGMY11) and a downstream pool of 13 oligonucleotides (PGMY09), thereby avoiding use of degenerate bases that yield irreproducible primer syntheses. The performance of the PGMY09-PGMY11 (PGMY09/11) primer system relative to that of the standard MY09/11 system was evaluated with a set of 262 cervicovaginal lavage specimens. There was a 91.5% overall agreement between the two systems (kappa = 0.83; P < 0.001). The PGMY09/11 system appeared to be significantly more sensitive than the MY09/11 system, detecting an additional 20 HPV-positive specimens, for a prevalence of 62.8% versus a prevalence of 55.1% with the MY09/11 system (McNemar's chi(2) = 17.2; P < 0.001). The proportion of multiple infections detected increased with the PGMY09/11 system (40. 0 versus 33.8% of positive infections). HPV types 26, 35, 42, 45, 52, 54, 55, 59, 66, 73, and MM7 were detected at least 25% more often with the PGMY09/11 system. The PGMY09/11 primer system affords an increase in type-specific amplification sensitivity over that of the standard MY09/11 primer system. This new primer system will be useful in assessing the natural history of HPV infections, particularly when the analysis requires HPV typing.
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              Papillomaviruses in the causation of human cancers - a brief historical account.

              Approximately 35 years ago a role of human papillomaviruses (HPV) in cervical cancer has been postulated. Today it is well established that this very heterogeneous virus family harbours important human carcinogens, causing not only the vast majority of cervical, but also a substantial proportion of other anogenital and head and neck cancers. In addition, specific types have been linked to certain cutaneous cancers. In females, HPV infections on a global scale account for more than 50% of infection-linked cancers, in males for barely 5%. Vaccines against the high risk HPV types 16 and 18 represent the first preventive vaccines directly developed to protect against a major human cancer (cervical carcinoma). This review will cover some of the historical aspects of papillomavirus research; it tries briefly to analyze the present state of linking HPV to human cancers and will discuss some emerging developments.
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                Author and article information

                Journal
                1886
                European Journal of Microbiology and Immunology
                EuJMI
                Akadémiai Kiadó
                2062-8633
                December 2018
                : 8
                : 4
                : 107-111
                Affiliations
                [ 1 ]Department of Gynaecology and Gynaecologic Oncology, University Medical Center Hamburg-Eppendorf , Germany
                [ 2 ]Department of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf , Germany
                [ 3 ]Department of Otorhinolaryngology, Head and Neck Surgery and Oncology, University Medical Centre Hamburg-Eppendorf , Germany
                [ 4 ]Department of Otolaryngology, Head and Neck Surgery, Asklepios Klinik Hamburg Altona , Germany
                [ 5 ] HNO-in-Altona, Private Praxis of Otorhinolaryngology , Hamburg, Germany
                [ 6 ] Tagesklinik Altonaer Strasse, Private Praxis of Gynaecology , Hamburg, Germany
                Author notes
                [*]

                Author for correspondence: Department of Gynaecology and Gynaecologic Oncology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; Tel: +49 407410 52510; Fax: +49407410 40070; E-mail: . d.grimm@ 123456uke.de

                Article
                10.1556/1886.2018.00018
                6348707
                8d04ec4f-dd38-4579-9c40-2bef73800cbd
                © 2018 The Author(s)

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and reproduction in any medium for non-commercial purposes, provided the original author and source are credited, a link to the CC License is provided, and changes - if any - are indicated.

                History
                : 10 July 2018
                : 18 July 2018
                : 12 December 2018
                Page count
                Pages: 5
                Categories
                Original Research Paper

                Medicine,Immunology,Health & Social care,Microbiology & Virology,Infectious disease & Microbiology
                cervical cancer (CC),HSIL,CIN,human papillomavirus (HPV),sexual transmitted disease,oropharyngeal squamous cell carcinoma (OSCC)

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