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      HPV-related oropharyngeal cancer prevalence in a middle eastern population using E6/E7 PCR

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          Abstract

          Background

          Given the paucity of data and widely variable rates that have been reported, the main objective of this study was to examine the prevalence of HPV-positivity in oropharyngeal squamous cell carcinoma (OPSCC) in Middle Eastern patients presenting to one of the region’s largest tertiary care centers using polymerase chain reaction (PCR) amplification of the HPV E6/E7 oncogenes, a highly sensitive and specific method of detection.

          Methods

          Medical charts and archived pathological specimens were obtained for patients diagnosed with biopsy proven oropharyngeal cancer who presented to the American University of Beirut Medical Center between 1972 and 2017. DNA was extracted from paraffin-embedded specimens and tested for 30 high-risk and low-risk papilloma viruses using the PCR-based EUROarray HPV kit (EuroImmun).

          Results

          A total of 57 patients with oropharyngeal cancer were initially identified; only 34 met inclusion/exclusion criteria and were included in the present study. Most patients were males (73.5%) from Lebanon (79.4%). The most common primary tumor site was in the base of tongue (50%), followed by the tonsil (41.2%). The majority of patients (85.3%) tested positive for HPV DNA.

          Conclusion

          The prevalence of HPV-positivity amongst Middle Eastern OPSCC patients, specifically those from Lebanon, may be far greater than previously thought. The Lebanese population and other neighboring Middle Eastern countries may require a more vigilant approach towards HPV detection and awareness. On an international level, further research is required to better elucidate non-classical mechanisms of HPV exposure and transmission.

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          Most cited references19

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          Human papillomavirus and head and neck cancer: a systematic review and meta-analysis.

          It has been suggested that the link between human papillomavirus (HPV) and head and neck squamous cell carcinoma (HNSCC) is specific to carcinoma of the tonsil. We systematically reviewed studies that tested for HPV16 exposure in anatomically defined sites in the head and neck and a control group. The association between HPV16 and cancer was strongest for tonsil (OR: 15.1, 95% CI: 6.8-33.7), intermediate for oropharynx (OR: 4.3, 95% CI: 2.1-8.9) and weakest for oral (OR: 2.0, 95% CI: 1.2-3.4) and larynx (OR: 2.0, 95% CI: 1.0-4.2). To investigate heterogeneity, further stratification by method of HPV16 detection, suggested that variation in the magnitude of the HPV-cancer association with cancer site was restricted to studies using ELISA: among studies using PCR, the magnitude of the summary odds ratios was similar across the four sites. The association between HPV16 infection and HNSCC in specific sites suggests the strongest and most consistent association is with tonsil cancer, and the magnitude of this association is consistent with an infectious aetiology. However, the method of viral detection may be an important source of heterogeneity. Resolution of this issue will require further studies using both methods, examining associations separately in different sites.
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            Meta analysis: HPV and p16 pattern determines survival in patients with HNSCC and identifies potential new biologic subtype

            Consistent discrepancies in the p16/HPV-positivity have been observed in head and neck squamous cell carcinoma (HNSCC). It is therefore questionable, if all HPV+ and/or p16+ tested cancers are HPV-driven. Patients down-staged according to the HPV-dependant TNM are at risk for undertreatment and data in clinical trials may be skewed due to false patient inclusion. We performed a meta-analysis to classify clinical outcomes of the distinct subgroups with combined p16 and HPV detection. 25 out of 1677 publications fulfilled the inclusion criteria. The proportion of the subgroups was 35.6% for HPV+/p16+, 50.4% for HPV−/p16−, 6.7% for HPV−/p16+ and 7.3% for HPV+/P16−. The HPV+/p16+ subgroup had a significantly improved 5-year overall-survival (OS) and disease-free-survival in comparison to others both for HNSCC and oropharyngeal cancers. The 5-year OS of the HPV−/p16+ HNSCC was intermediate while HPV+/p16− and HPV−/p16− had the shortest survival outcomes. The clearly distinct survival of HPV−/p16+ cancers may characterize a new relevant HPV-independent subtype yet to be biologically characterized. The possibility also exists that in some HPV+/p16+ cancers HPV is an innocent bystander and p16 is independently positive. Therefore, in perspective, HPV-testing should distinguish between bystander HPV and truly HPV-driven cancers to avoid potential undertreatment in HPV+ but non-HPV-driven HNSCC.
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              Rising prevalence of human papillomavirus-related oropharyngeal cancer in Australia over the last 2 decades.

              This study provides Australian data on the characteristics of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (SCC) over the last 2 decades.
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                Author and article information

                Contributors
                ik08@aub.edu.lb
                rm17@aub.edu.lb
                Journal
                Infect Agent Cancer
                Infect. Agents Cancer
                Infectious Agents and Cancer
                BioMed Central (London )
                1750-9378
                6 January 2020
                6 January 2020
                2020
                : 15
                : 1
                Affiliations
                [1 ]ISNI 0000 0004 0581 3406, GRID grid.411654.3, Department of Otolaryngology Head and Neck Surgery, , American University of Beirut Medical Center, ; 6th Floor, Hamra, Beirut, 1107 2020 Lebanon
                [2 ]ISNI 0000 0004 0581 3406, GRID grid.411654.3, Department of Radiation Oncology, , American University of Beirut Medical Center, ; Beirut, Lebanon
                [3 ]ISNI 0000 0004 0581 3406, GRID grid.411654.3, Department of Pathology and Laboratory Medicine, , American University of Beirut Medical Center, ; 2nd Floor, Hamra, Beirut, 1107 2020 Lebanon
                [4 ]ISNI 0000 0004 1936 9801, GRID grid.22903.3a, Biostatistics Unit, Clinical Research Institute, Faculty of Medicine, , American University of Beirut, ; Beirut, Lebanon
                Article
                268
                10.1186/s13027-019-0268-z
                6945694
                31921331
                213bc12e-a7bd-4ada-afba-70c8f0a7d54f
                © The Author(s). 2020

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 15 November 2019
                : 31 December 2019
                Funding
                Funded by: American University of Beirut
                Award ID: OTO-RM-03
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Oncology & Radiotherapy
                oropharyngeal cancer,head and neck squamous cell carcinoma,human papilloma virus,middle east,lebanon

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