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      An updated systemic review and meta-analysis on human papillomavirus in breast carcinogenesis

      systematic-review

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          Abstract

          Background

          Breast Cancer (BC) stands out as the widely prevalent malignancy among all the types of cancer affecting women worldwide. There is significant evidence that the pathogenicity of BC may be altered by Human Papillomavirus (HPV) infection; however, conclusive data are not yet available.

          Methods

          By searching five databases, including EMBASE, IBECS, PubMed, Scopus, Science Direct, Google Scholar, and Web of Science, a thorough systematic analysis was conducted on the prevalence of HPV in BC patients from 1990 to June 30, 2022. After applying extensive eligibility criteria, we selected 74 publications for further analysis based on the prevalence of HPV infections in breast tissues. All of the data were analyzed using a random-effects meta-analysis, Cochran Q test and I 2 statistic were used to calculate the heterogeneity of the prevalence among these studies using subgroup analysis. Variations in the HPV prevalence estimates in different subgroups were evaluated by subgroup meta-analysis.

          Results

          In total, 3156 studies were initially screened, resulting in 93 full-text studies reviewed, with 74 meeting inclusion criteria. Among a total of 7156 BC biopsies, the pool prevalence of HPV was 25.6% (95% CI= 0.24-0.33, τ2 = 0.0369 with significant heterogeneity between estimates ( I 2 = 97% and p< 0.01). Consequently, 45 studies with available controls were further studied, and the prevalence of HPV in case-control studies was 26.2% with overall odds 5.55 (95% CI= 3.67-8.41, I 2 = 38%, τ2 = 1.4878, p< 0.01). Further subgroup analysis of HPV revealed HPV-16 had a maximum prevalence of 9.6% (95% CI= 3.06-11.86, I 2 = 0%, τ2 = 0.6111, p< 0.01). Among different geographical regions, Europe reported the maximum prevalence of HPV, i.e., 39.2% (95% CI=1.29-7.91, I 2 = 18%, τ2 = 1.2911, p< 0.01). Overall distribution showed HPV-18 was a frequent HPV subtype reported in Australia.

          Conclusion

          Current study provides a global estimate of HPV prevalence in BC patients and demonstrates a significant association between this virus and BC etiology. Nevertheless, we recommend further investigation into the underlying mechanism is essential to validate this hypothesis.

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          Most cited references142

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Global Cancer Statistics, 2002

            Estimates of the worldwide incidence, mortality and prevalence of 26 cancers in the year 2002 are now available in the GLOBOCAN series of the International Agency for Research on Cancer. The results are presented here in summary form, including the geographic variation between 20 large "areas" of the world. Overall, there were 10.9 million new cases, 6.7 million deaths, and 24.6 million persons alive with cancer (within three years of diagnosis). The most commonly diagnosed cancers are lung (1.35 million), breast (1.15 million), and colorectal (1 million); the most common causes of cancer death are lung cancer (1.18 million deaths), stomach cancer (700,000 deaths), and liver cancer (598,000 deaths). The most prevalent cancer in the world is breast cancer (4.4 million survivors up to 5 years following diagnosis). There are striking variations in the risk of different cancers by geographic area. Most of the international variation is due to exposure to known or suspected risk factors related to lifestyle or environment, and provides a clear challenge to prevention.
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              Worldwide burden of cancer attributable to HPV by site, country and HPV type

              HPV is the cause of almost all cervical cancer and is responsible for a substantial fraction of other anogenital cancers and oropharyngeal cancers. Understanding the HPV‐attributable cancer burden can boost programs of HPV vaccination and HPV‐based cervical screening. Attributable fractions (AFs) and the relative contributions of different HPV types were derived from published studies reporting on the prevalence of transforming HPV infection in cancer tissue. Maps of age‐standardized incidence rates of HPV‐attributable cancers by country from GLOBOCAN 2012 data are shown separately for the cervix, other anogenital tract and head and neck cancers. The relative contribution of HPV16/18 and HPV6/11/16/18/31/33/45/52/58 was also estimated. 4.5% of all cancers worldwide (630,000 new cancer cases per year) are attributable to HPV: 8.6% in women and 0.8% in men. AF in women ranges from 20% in India and sub‐Saharan Africa. Cervix accounts for 83% of HPV‐attributable cancer, two‐thirds of which occur in less developed countries. Other HPV‐attributable anogenital cancer includes 8,500 vulva; 12,000 vagina; 35,000 anus (half occurring in men) and 13,000 penis. In the head and neck, HPV‐attributable cancers represent 38,000 cases of which 21,000 are oropharyngeal cancers occurring in more developed countries. The relative contributions of HPV16/18 and HPV6/11/16/18/31/33/45/52/58 are 73% and 90%, respectively. Universal access to vaccination is the key to avoiding most cases of HPV‐attributable cancer. The preponderant burden of HPV16/18 and the possibility of cross‐protection emphasize the importance of the introduction of more affordable vaccines in less developed countries.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                11 August 2023
                2023
                : 13
                : 1219161
                Affiliations
                [1] 1 Medical Research Center, The Second Affiliated Hospital of Zhengzhou University , Zhengzhou, China
                [2] 2 Department of Medical Laboratory Technology, The University of Haripur , Haripur, Khyber Pakhtunkhwa, Pakistan
                [3] 3 Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine , Nashville, TN, United States
                [4] 4 Department of Biomedical Informatics, Vanderbilt University School of Medicine , Nashville, TN, United States
                [5] 5 Department of Mathematics and Statistics, The University of Haripur , Haripur, Khyber Pakhtunkhwa, Pakistan
                [6] 6 Department of Pathology, Shaukat Khanum Memorial Cancer Hospital and Research Center (SKMCH&RC) , Lahore, Pakistan
                [7] 7 Zhengzhou Key Laboratory of Children’s Infection and Immunity, Children’s Hospital Affiliated to Zhengzhou University , Zhengzhou, China
                [8] 8 Henan Key Laboratory of Precision Diagnosis of Respiratory Infectious Diseases, Zhengzhou Key Laboratory of Precision Diagnosis of Respiratory Infectious Diseases, The Second Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan, China
                Author notes

                Edited by: Ala-Eddin Al Moustafa, Qatar University, Qatar

                Reviewed by: James Sutherland Lawson, University of New South Wales, Australia; J. Guilherme Gonçalves - Nobre, University of Lisbon, Portugal

                Article
                10.3389/fonc.2023.1219161
                10498127
                37711194
                608bedfe-0018-4127-9622-3024783bb5a6
                Copyright © 2023 Awan, Khattak, Ahmed, Guo, Akhtar, Kamran, Yongjing, Liu and Khan

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 08 May 2023
                : 17 July 2023
                Page count
                Figures: 12, Tables: 0, Equations: 0, References: 148, Pages: 16, Words: 4456
                Funding
                The Science and Technology Developmental Plan of Henan Province (Grant No.232102520025), The National Foreign Expert Program of China (Grant No. QN2022026001L), and Zhengzhou University start-up grant for high talent full time researchers
                Categories
                Oncology
                Systematic Review
                Custom metadata
                Breast Cancer

                Oncology & Radiotherapy
                human papillomavirus,breast cancer,viral oncology,hpv subtypes,breast carcinogenesis,meta-analysis,polymerase chain reaction (pcr),case-control studies

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