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      Are HPV oncogenic viruses involved in salivary glands tumorigenesis?

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          Abstract

          The association between different viruses and cancer is well acknowledged in human pathology. However, the precise understanding of how oncogenic viruses intervene in the development of cancer of salivary glands (SGs) remains incomplete. Our review aimed to explore the current literature regarding SGs cancer to evaluate the potential involvement of human papillomaviruses (HPVs) in their development. Our work hypothesis suggests that viruses may be involved in these tumors’ immunogenicity. The literature analysis showed HPV-positive detection in different head and neck malignancies, added to variable risk factors and a constant increasing incidence rate. HPV tumorigenesis mechanism is complex, involving E6 and E7 HPV oncoproteins. Additionally, the reported findings generally support the relationship between SGs cancer and high oncogenic subtypes 16 and 18. However, the pathogenic contribution of HPV subtypes 11, 33, 45, 52, 56, and 59 is controversial and further research may clarify their potential involvement in the SG tumor’s development. This literature review may enhance the understanding of the role of viral contribution as an etiopathogenic co-factor in SG carcinogenesis. Thus, these data may add value to innovative concepts and treatment strategies development, given that virus-induced tumors can be prevented by targeted immunization, added to oncolytic or viral therapy.

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          Human Papillomavirus and Cervical Cancer

          E. M. Burd (2003)
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            HPV-associated oropharyngeal cancer: epidemiology, molecular biology and clinical management

            Human papillomavirus (HPV)-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) has one of the most rapidly increasing incidences of any cancer in high-income countries. The most recent (8th) edition of the UICC/AJCC staging system separates HPV+ OPSCC from its HPV-negative (HPV−) counterpart to account for the improved prognosis seen in the former. Indeed, owing to its improved prognosis and greater prevalence in younger individuals, numerous ongoing trials are examining the potential for treatment de-intensification as a means to improve quality of life while maintaining acceptable survival outcomes. In addition, owing to the distinct biology of HPV+ OPSCCs, targeted therapies and immunotherapies have become an area of particular interest. Importantly, OPSCC is often detected at an advanced stage owing to a lack of symptoms in the early stages; therefore, a need exists to identify and validate possible diagnostic biomarkers to aid in earlier detection. In this Review, we provide a summary of the epidemiology, molecular biology and clinical management of HPV+ OPSCC in an effort to highlight important advances in the field. Ultimately, a need exists for improved understanding of the molecular basis and clinical course of this disease to guide efforts towards early detection and precision care, and to improve patient outcomes.
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              The human papillomavirus replication cycle, and its links to cancer progression: a comprehensive review.

              HPVs (human papillomaviruses) infect epithelial cells and their replication cycle is intimately linked to epithelial differentiation. There are over 200 different HPV genotypes identified to date and each displays a strict tissue specificity for infection. HPV infection can result in a range of benign lesions, for example verrucas on the feet, common warts on the hands, or genital warts. HPV infects dividing basal epithelial cells where its dsDNA episomal genome enters the nuclei. Upon basal cell division, an infected daughter cell begins the process of keratinocyte differentiation that triggers a tightly orchestrated pattern of viral gene expression to accomplish a productive infection. A subset of mucosal-infective HPVs, the so-called 'high risk' (HR) HPVs, cause cervical disease, categorized as low or high grade. Most individuals will experience transient HR-HPV infection during their lifetime but these infections will not progress to clinically significant cervical disease or cancer because the immune system eventually recognizes and clears the virus. Cancer progression is due to persistent infection with an HR-HPV. HR-HPV infection is the cause of >99.7% cervical cancers in women, and a subset of oropharyngeal cancers, predominantly in men. HPV16 (HR-HPV genotype 16) is the most prevalent worldwide and the major cause of HPV-associated cancers. At the molecular level, cancer progression is due to increased expression of the viral oncoproteins E6 and E7, which activate the cell cycle, inhibit apoptosis, and allow accumulation of DNA damage. This review aims to describe the productive life cycle of HPV and discuss the roles of the viral proteins in HPV replication. Routes to viral persistence and cancer progression are also discussed.
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                Author and article information

                Journal
                Rom J Morphol Embryol
                Rom J Morphol Embryol
                RJME
                Romanian Journal of Morphology and Embryology
                Academy of Medical Sciences, Romanian Academy Publishing House, Bucharest
                1220-0522
                2066-8279
                Jul-Sep 2024
                30 September 2024
                : 65
                : 3
                : 395-407
                Affiliations
                [1 ] Department of Morphofunctional Sciences I, Grigore T. Popa University of Medicine and Pharmacy, Iaşi, Romania
                [2 ] Department of Histopathology, Institute of Legal Medicine, Iaşi, Romania
                [3 ] Department of Pathology, Elena Doamna Clinical Hospital of Obstetrics and Gynecology, Iaşi, Romania
                Author notes
                Corresponding Author: Raluca Anca Balan, Professor, MD, PhD Department of Morphofunctional Sciences I Grigore T. Popa University of Medicine and Pharmacy 16 University Street 700115 Iaşi Romania + 40720–550 530 raluca.balan@ 123456umfiasi.ro
                Article
                650324395407
                10.47162/RJME.65.3.02
                11657354
                39529333
                6291fe87-1bc8-414d-b276-6d52138f6ea1
                Copyright © 2024, Academy of Medical Sciences, Romanian Academy Publishing House, Bucharest

                This is an open-access article distributed under the terms of a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International Public License, which permits unrestricted use, adaptation, distribution and reproduction in any medium, non-commercially, provided the new creations are licensed under identical terms as the original work and the original work is properly cited.

                History
                : 17 August 2024
                : 28 October 2024
                Categories
                Review

                human papillomaviruses , salivary gland tumors , virus-induced tumors , e6 , e7 , hr-hpv

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