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      HPV prevalence and genotype distribution in 2,306 patients with cervical squamous cell carcinoma in central and eastern China

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          Abstract

          Background

          To explore the positivity rate and genotype distribution of human papillomavirus (HPV) in cervical squamous cell carcinoma (CSCC) tissues in central and eastern China and to provide theoretical basis for cervical cancer screening and prophylactic HPV vaccine development in China.

          Methods

          DNA was extracted from paraffin-embedded tissues of CSCC samples and exfoliated cervical cells of cervical cancer screening populations. 23 HPV genotypes were detected by combining polymerase chain reaction (PCR) and reverse dot hybridized gene chip detection technology in 2,306 CSCC tissues and 10,245 cervical cancer screening populations. The genotype distribution of HPV infection was analyzed.

          Results

          The overall infection rate of HPVs in 2,306 CSCC patients was 92.71%. The frequency of single-type HPV infection and multiple-type HPV infection were 86.48% and 13.51%, respectively. The most common HPV genotypes detected in Chinese CSCC tissues were HPV-16, HPV-18, HPV-31, HPV-33, HPV-45, HPV-52, HPV-58, and HPV-59. The overall positivity rate of these eight high-risk HPV (HR-HPV) genotypes in HPV-positive CSCC was as high as 96.91%. Of which the positivity rate of seven HR-HPV genotypes related to nine-valent HPV vaccines in HPV-positive CSCC was 95.09%. Meanwhile, the overall infection rates of HR-HPV and low-risk HPV (LR-HPV) in female aged 35–64 years who underwent cervical cancer screening were 13.16% and 1.32%, respectively. The high-frequency HR-HPV genotypes in cervical cancer screening women were HPV-52, HPV-58, HPV-16, HPV-53, HPV-68, HPV-39, HPV-51, and HPV-56, with positivity rates of 2.25%, 1.60%, 1.31%, 1.22%, 0.93%, 0.92%, 0.78%, and 0.74%, respectively.

          Conclusion

          Among women screened for cervical cancer in China, detecting the 8 high-frequency HR-HPV genotypes can reduce technical difficulty and reagent costs, while also improving the efficiency and effectiveness of cervical cancer screening. HPV genotyping assists gynecologists in assessing the risk of HR-HPV-positive cervical intraepithelial neoplasia and guiding them in implementing appropriate interventions. Furthermore, HPV genotyping is helpful for doctors to follow up HR-HPV-positive women and to evaluate the protective effect of HPV vaccine.

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          Most cited references30

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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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            Human papillomavirus is a necessary cause of invasive cervical cancer worldwide.

            A recent report that 93 per cent of invasive cervical cancers worldwide contain human papillomavirus (HPV) may be an underestimate, due to sample inadequacy or integration events affecting the HPV L1 gene, which is the target of the polymerase chain reaction (PCR)-based test which was used. The formerly HPV-negative cases from this study have therefore been reanalyzed for HPV serum antibodies and HPV DNA. Serology for HPV 16 VLPs, E6, and E7 antibodies was performed on 49 of the 66 cases which were HPV-negative and a sample of 48 of the 866 cases which were HPV-positive in the original study. Moreover, 55 of the 66 formerly HPV-negative biopsies were also reanalyzed by a sandwich procedure in which the outer sections in a series of sections are used for histological review, while the inner sections are assayed by three different HPV PCR assays targeting different open reading frames (ORFs). No significant difference was found in serology for HPV 16 proteins between the cases that were originally HPV PCR-negative and -positive. Type-specific E7 PCR for 14 high-risk HPV types detected HPV DNA in 38 (69 per cent) of the 55 originally HPV-negative and amplifiable specimens. The HPV types detected were 16, 18, 31, 33, 39, 45, 52, and 58. Two (4 per cent) additional cases were only HPV DNA-positive by E1 and/or L1 consensus PCR. Histological analysis of the 55 specimens revealed that 21 were qualitatively inadequate. Only two of the 34 adequate samples were HPV-negative on all PCR tests, as against 13 of the 21 that were inadequate ( p< 0.001). Combining the data from this and the previous study and excluding inadequate specimens, the worldwide HPV prevalence in cervical carcinomas is 99.7 per cent. The presence of HPV in virtually all cervical cancers implies the highest worldwide attributable fraction so far reported for a specific cause of any major human cancer. The extreme rarity of HPV-negative cancers reinforces the rationale for HPV testing in addition to, or even instead of, cervical cytology in routine cervical screening. Copyright 1999 John Wiley & Sons, Ltd.
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              Cancer incidence and mortality in China, 2016

              Background National Cancer Center (NCC) of China annually reports the nationwide statistics for cancer incidence and mortality using population-based cancer registry data from all available cancer registries in China. Methods There were a total of 487 registries which reported high quality data of cancer incidence and mortality across China in 2016. The nationwide numbers of new cancer cases and deaths were estimated using the pooled cancer registry data, which were stratified by area (urban/rural), sex, age group (0, 1-4, 5-9, 10-14…85+) and cancer site for incidence and mortality, and then multiplied by corresponding national population. The world Segi's population was applied for the calculation of age-standardized rates. Results About 4,064,000 new cancer cases and 2,413,500 new cancer deaths occurred in China in 2016. Cancers of the lung, colon-rectum, stomach, liver and female breast were the top five common cancers, accounting for 57.4% of total cancer new cases. Cancers of the lung, liver, stomach, colon-rectum and esophagus were the five leading causes of cancer deaths, accounting for 69.3% of total cancer deaths. The crude and age-standardized incidence rates (ASIR) were 293.91 and 186.46 per 100,000 population, respectively. The crude mortality rate was 174.55/100,000 and the age-standardized mortality rate (ASMR) was 105.19/100,000. The ASIR was higher but the ASMR was lower in urban areas than that in rural areas. In past decades, the ASIR was relatively stable in males, but significantly increased by about 2.3% per year in females for overall cancers combined. In contrast, the ASMR significantly decreased by about 1.2% per year for both sexes during 2000-2016. Notably, the cancer-specific ASIR and ASMR of esophageal, stomach, and liver cancers decreased significantly, whereas both rates for cancers of the colon-rectum, prostate, female breast, cervix, and thyroid increased significantly. Conclusions Cancer remains a major public health problem in China, which demands long-term collaborative efforts of a broad community. With the national guideline on cancer prevention and control, tailored cancer prevention and control programs are needed in different regions to help reduce the burden of these highly fatal diseases in China.
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                Author and article information

                Contributors
                Journal
                Front Public Health
                Front Public Health
                Front. Public Health
                Frontiers in Public Health
                Frontiers Media S.A.
                2296-2565
                28 August 2023
                2023
                : 11
                : 1225652
                Affiliations
                [1] 1Department of Pathology, Nanjing Lishui People’s Hospital (Zhongda Hospital Lishui Branch), Southeast University , Nanjing, China
                [2] 2Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Centre for Systems Biomedicine, Shanghai Jiao Tong University , Shanghai, China
                [3] 3Nanjing Jiangning District Maternal and Child Health and Family Planning Service Center , Nanjing, China
                [4] 4Department of Pathology, Yancheng No.1 People’s Hospital , Yancheng, China
                [5] 5Department of Pathology, Jingjiang People’s Hospital , Taizhou, China
                [6] 6Department of Pathology, Jinhu County People’s Hospital , Huai’an, China
                [7] 7Department of Pathology, Dantu District People’s Hospital of Zhenjiang , Zhenjiang, China
                [8] 8Department of Pathology, People’s Hospital of Yangzhong City , Yangzhong, China
                [9] 9Department of Central Laboratory, Jiangsu Health Vocational College , Nanjing, China
                [10] 10Department of Pathology, Nanjing Meishan Hospital , Nanjing, China
                [11] 11Department of Pathology, Nanjing Hospital of Traditional Chinese Medicine , Nanjing, China
                [12] 12Department of Pathology, Linyi Cancer Hospital , Linyi, China
                [13] 13The Cross-Strait Precision Medicine Association HPV Infection Disease Professional Committee , Nanjing, China
                Author notes

                Edited by: Aleksandra Barac, University of Belgrade, Serbia

                Reviewed by: Saumya Pandey, IndiraIVF Hospital, India; Zhihua Ou, Beijing Genomics Institute (BGI), China; Basem Bas Fares, Developer, Hertzelia, Israel

                *Correspondence: Jian Huang, jianhuang@ 123456sjtu.edu.cn

                These authors have contributed equally to this work and share first authorship

                Article
                10.3389/fpubh.2023.1225652
                10493278
                37701907
                324596bf-e057-47bb-852c-ab92708fdcec
                Copyright © 2023 Han, Huang, Ye, Zou, Lan, Chen, Jiang, Wang, Xia, Luo, Li, Geng, Wang and Huang.

                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
                : 19 May 2023
                : 09 August 2023
                Page count
                Figures: 5, Tables: 2, Equations: 0, References: 32, Pages: 11, Words: 6910
                Funding
                Funded by: Science and Technology Innovation Action Plan Startup Project (Sail Special) of Shanghai
                Award ID: 22YF1420500
                Funded by: Fundamental Research Funds for the Central Universities, doi 10.13039/501100012226;
                Award ID: KLSB2022QN-01
                Funded by: Medical-Industrial Crossover Research Fund of Shanghai Jiao Tong University
                Award ID: YG2022QN070
                Award ID: 19X190020005
                Funded by: National Natural Science Foundation of China, doi 10.13039/501100001809;
                Award ID: 81872274
                Categories
                Public Health
                Original Research
                Custom metadata
                Infectious Diseases: Epidemiology and Prevention

                human papillomavirus,cervical squamous cell carcinoma,high-risk genotypes,prevalence,china

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