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Application of Machine Learning Algorithms for Risk Stratification and Efficacy Evaluation in Cervical Cancer Screening Among the ASCUS/LSIL Population: Evidence from the Korean HPV Cohort Study
Heekyoung Song, Hong Yeon Lee, Shin Ah Oh, Jaehyun Seong, Soo Young Hur, Youn Jin Choi
Received May 15, 2024  Accepted September 5, 2024  Published online September 6, 2024  
DOI: https://doi.org/10.4143/crt.2024.465    [Epub ahead of print]
AbstractAbstract PDFSupplementary Material
Purpose
We assessed human papillomavirus (HPV) genotype-based risk stratification and the efficacy of cytology testing for cervical cancer screening in patients with atypical squamous cells of undetermined significance (ASCUS)/low-grade squamous intraepithelial lesion (LSIL).
Materials and Methods
Between 2010 and 2021, we monitored 1,273 HPV-positive women with ASCUS/LSIL every 6 months for up to 60 months. HPV infections were categorized as persistent (HPV positivity consistently observed post-enrollment), negative (HPV negativity consistently observed post-enrollment), or non-persistent (neither consistently positive nor negative). HPV genotypes were grouped into high-risk (Hr) groups 1 (types 16, 18, 31, 33, 45, 52, and 58) and 2 (types 35, 39, 51, 56, 59, 66, and 68) and a low-risk group. Hr1 was subdivided into types (a) 16 and 18; (b) 31, 33, and 45; and (c) 52 and 58. Cox regression and machine learning (ML) algorithms were used to analyze progression rates.
Results
Among 1,273 participants, 17.6% with persistent HPV infections experienced disease progression versus no progression in the HPV-negative group (p < 0.001). Cox analysis revealed the highest hazard ratios (HRs) for Hr1-a (11.6, p < 0.001), followed by Hr1-b (9.26, p < 0.001) and Hr1-c (7.21, p < 0.001). HRs peaked at 12-24 months, with Hr1-a maintaining significance at 24-36 months (10.7, p=0.034). ML analysis identified the final cytology change pattern as the most significant factor, with 14-15 months the optimal time for detecting progression from the first examination.
Conclusion
In ASCUS/LSIL cases, follow-up strategies should be based on HPV risk types. Annual follow-up was the most effective monitoring for detecting progression/regression.

Citations

Citations to this article as recorded by  
  • Geneticsbiologiesingle cell and expression analysis for erectile dysfunction and cervical cancer targets
    Tengfei Zhao, Yangyang Li, Huixue Liu, Chongxin Tong
    Discover Oncology.2024;[Epub]     CrossRef
  • 479 View
  • 52 Download
  • 1 Crossref
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Gynecologic cancer
Predicted Cervical Cancer Prevention: Impact of National HPV Vaccination Program on Young Women in South Korea
Kyeongmin Kwak, Seung-sik Hwang
Cancer Res Treat. 2024;56(3):898-908.   Published online January 15, 2024
DOI: https://doi.org/10.4143/crt.2023.981
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to evaluate the effectiveness of the national human papillomavirus (HPV) vaccination program of South Korea among its entire female population, particularly among younger age groups.
Materials and Methods
We first predicted the incidence of cervical cancer over the next 20 years (2021-2040) using the Nordpred package based on Møller’s age-period-cohort model under several scenarios for the national HPV vaccination program. We calculated the potential impact fractions and proportional differences under the current national vaccination programs, and alternative scenarios using the no-vaccination assumption as a reference.
Results
We estimated that the current national vaccination program would prevent 4.13% of cervical cancer cases and reduce the age-standardized incidence rate (ASR) by 8.79% in the overall population by 2036-2040. Under the alternative scenario of implementing the nine-valent vaccine, 5.13% of cervical cancer cases could be prevented and the ASR reduced by 10.93% during the same period. In another scenario, expanding the vaccination age to 9-17 years could prevent 10.19% of cervical cancer cases, with the ASR reduced by 18.57% during the same period. When restricted to ages < 40 years, the prevention effect was remarkably greater. We predict that the current national HPV program will reduce its incidence by more than 30% between 2036 and 2040 in women aged < 40 years.
Conclusion
The effectiveness of the vaccination program in reducing the incidence of cervical cancer was confirmed, with a considerable impact anticipated in younger age groups.
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Plasma Cell-Free DNA in Uterine Cervical Cancer: Therapeutic Monitoring and Prognostic Values after Radical Radiotherapy
Jae Sik Kim, Sunah Yang, Kyeonghun Jeong, Dong-Yun Kim, Kwangsoo Kim, Hyun-Cheol Kang
Cancer Res Treat. 2023;55(2):659-670.   Published online December 12, 2022
DOI: https://doi.org/10.4143/crt.2022.1440
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
In the present study, we aimed to establish a liquid biopsy-based monitoring method using peripheral blood cell-free DNA (cfDNA) for patients with cervical cancer who underwent radical radiotherapy (RT).
Materials and Methods
Twenty-five patients with cervical cancer were prospectively recruited and treated with external beam RT and brachytherapy. In all patients, except one, chemotherapy was administered concurrently during RT. Whole peripheral blood samples were obtained at least twice from each patient. We performed next-generation sequencing (NGS) for the target-captured libraries (67 oncogenes and human papillomavirus [HPV] type 16/18) using 64 plasma cfDNA samples from the 25 participants. The ratio of HPV cfDNA and the variant allele frequency (VAF) in cfDNA was calculated, and their dynamic changes were monitored. The median follow-up duration was 25.4 months.
Results
In total, we identified 21,866 cfDNA variants. ARID1A and frameshift variants occupied the largest portion of altered genes and HIGH-grade variant types, respectively. In most cases, tumor shrinkage was followed by a decrease in the HPV ratio; however, an increase in HPV ratio indicated distant metastasis, despite the reduced tumor size. The initial HPV ratio reflecting the tumor burden was likely associated with treatment outcomes (p = 0.16). We did not determine a role for serial changes in the VAF in cfDNA.
Conclusion
Our findings suggest that the HPV cfDNA ratio, calculated after targeted NGS, may be valuable for monitoring and predicting treatment responses. Accordingly, further validation of these findings is warranted.

Citations

Citations to this article as recorded by  
  • Circulating cell-free DNA as a diagnostic and prognostic marker for cervical cancer
    Preetiparna Parida, Gayathri Baburaj, Mahadev Rao, Shirley Lewis, Rama Rao Damerla
    International Journal of Gynecological Cancer.2024; 34(2): 307.     CrossRef
  • Prognostic value of circulating short-length DNA fragments in unresected glioblastoma patients
    Arthur Daban, Ludivine Beaussire-Trouvay, Émilie Lévêque, Cristina Alexandru, Isabelle Tennevet, Olivier Langlois, Ovidiu Veresezan, Florent Marguet, Florian Clatot, Frédéric Di Fiore, Nasrin Sarafan-Vasseur, Maxime Fontanilles
    Translational Oncology.2024; 42: 101897.     CrossRef
  • Cervical Cancer Genetic Profile through Circulating Tumor DNA: What Can We Learn from Blood?
    Sevastiani Antonouli, Valentina Di Nisio, Nikoletta Daponte, Athina-Ioanna Daponte, Alexandros Daponte
    Biomolecules.2024; 14(7): 825.     CrossRef
  • High throughput sequencing technology and its clinical application in circulating tumor DNA detection in patients with tumors.
    Chonghe Xu, Dangui Zhou, Mei Zhu
    Investigación Clínica.2024; 65(4): 476.     CrossRef
  • 4,506 View
  • 183 Download
  • 6 Web of Science
  • 4 Crossref
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Head and Neck Cancer
Recent Treatment Patterns of Oropharyngeal Cancer in Korea Based on the Expert Questionnaire Survey of the Korean Society for Head and Neck Oncology (KSHNO)
Kyu Hye Choi, Jin Ho Song, Yeon-Sil Kim, Ji-hoon Kim, Woo-Jin Jeong, Inn-Chul Nam, Jin Ho Kim, Hee Kyung Ahn, Sang Hoon Chun, Hyun Jun Hong, Young-Hoon Joo, Young-Gyu Eun, Sung Ho Moon, Jeongshim Lee
Cancer Res Treat. 2021;53(4):1004-1014.   Published online January 29, 2021
DOI: https://doi.org/10.4143/crt.2020.973
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The incidence of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) has increased, and staging and optimal therapeutic approaches are challenging. A questionnaire survey was conducted to investigate the controversial treatment policy of stage T2 OPC according to the N category and determine the opinions of multidisciplinary experts in Korea.
Materials and Methods
Five OPC scenarios were developed by the Subcommittee on Oropharyngeal Treatment Guidelines of the Korean Society for Head and Neck Oncology and distributed to experts of multidisciplinary treatment hospitals.
Results
Sixty-five experts from 45 institutions responded. For the HPV-positive T2N0M0 scenario, 67.7% of respondents selected surgery followed by definitive concurrent chemoradiotherapy (CCRT) or radiotherapy alone. For the T2N1M0 HPV-positive scenario, there was a notable difference in the selection of primary treatment by expert specialty; 53.9% of respondents selected surgery and 39.8% selected definitive CCRT as the primary treatment. For the T2N3M0 advanced HPV-positive scenario, 50.0% of respondents selected CCRT and 33.3% considered induction chemotherapy (IC) as the primary treatment. CCRT and IC were significantly more frequently selected for the HPV-related OPC cases (p=0.010). The interdepartmental variability showed that the head and neck surgeons and medical oncologists favored surgery, whereas the radiation oncologists preferably selected definitive CCRT (p < 0.001).
Conclusion
In this study, surgery was preferred for lymph node-negative OPC, and as lymph node metastasis progressed, CCRT tended to be preferred, and IC was administered. Clinical practice patterns by stage and HPV status showed differences according to expert specialty. Multidisciplinary consensus guidelines will be essential in the future.

Citations

Citations to this article as recorded by  
  • Controversies in Lung Cancer: Heterogeneity in Treatment Recommendations for Stage III NSCLC According to Disease Burden and Oncogenic Driver Alterations
    Jeremy P Harris, Dylann K Fujimoto, Misako Nagasaka, Eric Ku, Garrett Harada, Hari Keshava, Ali Mahtabifard, Javier Longoria, Niral Patel, Steven Seyedin, Aaron Simon, Allen Chen
    Clinical Lung Cancer.2022; 23(4): 333.     CrossRef
  • Survey of radiation field and dose in human papillomavirus-positive oropharyngeal cancer: is de-escalation actually applied in clinical practice?
    Kyu Hye Choi, Jin Ho Song, Yeon-Sil Kim, Sung Ho Moon, Jeongshim Lee, Young-Taek Oh, Dongryul Oh, Jin Ho Kim, Jun Won Kim
    Radiation Oncology Journal.2021; 39(3): 174.     CrossRef
  • 6,303 View
  • 157 Download
  • 3 Web of Science
  • 2 Crossref
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Gynecologic Cancer
Performance and Diagnostic Accuracy of Human Papillomavirus Testing on Self-Collected Urine and Vaginal Samples in a Referral Population
Hyun-Woong Cho, Jin Hwa Hong, Kyung Jin Min, Yung-Taek Ouh, Seok Ju Seong, Jun Hye Moon, Seong Hwan Cho, Jae Kwan Lee
Cancer Res Treat. 2021;53(3):829-836.   Published online December 24, 2020
DOI: https://doi.org/10.4143/crt.2020.1165
AbstractAbstract PDFPubReaderePub
Purpose
The study aimed to evaluate the diagnostic accuracy of polymerase chain reaction ‒based high-risk human papillomavirus (HPV) assays on self-collected vaginal and urine samples for detection of precancerous cervical lesions in referral population.
Materials and Methods
Women referred for colposcopy following abnormal cytology, were included this study. A total of 314 matched urine, vaginal, and cervical samples were collected. All samples were tested for HPV DNA using the RealTime HR-S HPV and Anyplex II HPV 28 assays. Primary endpoints were sensitivity for cervical intraepithelial neoplasia (CIN) 2+/CIN3+ and specificity for Result
The sensitivity of Realtime HR-S and Anyplex HPV assay was 93.13% (95% confidence interval [CI], 87.36 to 96.81) and 90.08% (95% CI, 83.63 to 94.61) for CIN2+ (n=130); specificity for Conclusion
The detection performance for hrHPV and CIN2+ on self-collected vaginal samples was comparable to that of clinician-collected cervical samples. On the other hand, HPV tests using urine were inferior to those using clinician-collected cervical samples in terms of detecting hrHPV and CIN2+.

Citations

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  • Diagnostic accuracy of human papillomavirus testing on self-collected samples among women referred for colposcopy
    ChunX Yan, Jiong Ma, Xia Zheng, Jing Shu, XiaoJ Wang, XiaoY Chen, Feng Gao, XiaoQ Li, ShanQ M, LongM Huang, XiaoT Yu, XueJ Chen
    Scientific Reports.2025;[Epub]     CrossRef
  • Variables that impact HPV test accuracy during vaginal self collection workflow for cervical cancer screening
    Laurence Vaughan, Devin Gary, Millie Shah, Lyndsay Lewellen, Laura Galbraith, Valentin Parvu
    Gynecologic Oncology Reports.2024; 54: 101421.     CrossRef
  • Clinical performance of a newly developed domestic urine‐based HPV test for cervical cancer screening in China
    Hui‐Fang Xu, Xue‐Lian Zhao, Shuang Zhao, Shang‐Ying Hu, Xun Zhang, Fang‐Hui Zhao, You‐Lin Qiao
    Journal of Medical Virology.2023;[Epub]     CrossRef
  • Can HPV Test on Random Urine Replace Self-HPV Test on Vaginal Self-Samples or Clinician-Collected Cervical Samples?
    Yu-Hsiang Shih, Lou Sun, Shih-Tien Hsu, Ming-Jer Chen, Chien-Hsing Lu
    International Journal of Women's Health.2023; Volume 15: 1421.     CrossRef
  • Preliminary Results of Feasibility and Acceptability of Self-Collection for Cervical Screening in Italian Women
    Illari Sechi, Narcisa Muresu, Mariangela V. Puci, Laura Saderi, Arcadia Del Rio, Andrea Cossu, Maria R. Muroni, Santina Castriciano, Marianna Martinelli, Clementina E. Cocuzza, Giovanni Sotgiu, Andrea Piana
    Pathogens.2023; 12(9): 1169.     CrossRef
  • Human papillomavirus testing using HPV APTIMA® assay and an external cellularity control in self‐collected samples
    Christophe Pasquier, Stéphanie Raymond, Delphine Duchanois, Karine Sauné, Kevin Oliveira‐Mendes, Christophe Vayssiere, Jacques Izopet
    Journal of Medical Virology.2023;[Epub]     CrossRef
  • Comparison of Different Self-Sampling Devices for Molecular Detection of Human Papillomavirus (HPV) and Other Sexually Transmitted Infections (STIs): A Pilot Study
    Illari Sechi, Clementina Cocuzza, Marianna Martinelli, Narcisa Muresu, Santina Castriciano, Giovanni Sotgiu, Andrea Piana
    Healthcare.2022; 10(3): 459.     CrossRef
  • The Potential of Urine for Human papillomavirus-related Cervical Cancer Prevention
    Maryame Lamsisi, Guorong Li, Celine Chauleur, Moulay Mustapha Ennaji, Thomas Bourlet
    Future Virology.2022; 17(7): 495.     CrossRef
  • Evaluation of BD Onclarity™ HPV Assay on Self-Collected Vaginal and First-Void Urine Samples as Compared to Clinician-Collected Cervical Samples: A Pilot Study
    Marianna Martinelli, Chiara Giubbi, Illari Sechi, Fabio Bottari, Anna Daniela Iacobone, Rosario Musumeci, Federica Perdoni, Narcisa Muresu, Andrea Piana, Robert Fruscio, Fabio Landoni, Clementina Elvezia Cocuzza
    Diagnostics.2022; 12(12): 3075.     CrossRef
  • Urine HPV in the Context of Genital and Cervical Cancer Screening—An Update of Current Literature
    Alexandros Daponte, George Michail, Athina-Ioanna Daponte, Nikoletta Daponte, George Valasoulis
    Cancers.2021; 13(7): 1640.     CrossRef
  • Diagnostic Test Accuracy of First-Void Urine Human Papillomaviruses for Presence Cervical HPV in Women: Systematic Review and Meta-Analysis
    Peter Bober, Peter Firment, Ján Sabo
    International Journal of Environmental Research and Public Health.2021; 18(24): 13314.     CrossRef
  • 6,650 View
  • 195 Download
  • 11 Crossref
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Type-Specific Viral Load and Physical State of HPV Type 16, 18, and 58 as Diagnostic Biomarkers for High-Grade Squamous Intraepithelial Lesions or Cervical Cancer
Jongseung Kim, Bu Kyung Kim, Dongsoo Jeon, Chae Hyeong Lee, Ju-Won Roh, Joo-Young Kim, Sang-Yoon Park
Cancer Res Treat. 2020;52(2):396-405.   Published online August 28, 2019
DOI: https://doi.org/10.4143/crt.2019.152
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
High rate of false-positive tests is a major obstacle to use human papillomavirus (HPV) detection as a diagnostic tool for high-grade squamous intraepithelial lesions or cervical cancer (HSIL+). We investigated whether type-specific viral load or physical state of HPV 16, 18, and 58 are useful biomarkers for HSIL+.
Materials and Methods
Type-specific viral loads of E6 and E2 genes in cervical cells from 240, 83, and 79 HPV 16–, 18–, and 58–infected women, respectively, were determined using real-time polymerase chain reaction. Viral loads were normalized to cellular DNA (copy/cell). Total and integrated viral loads and physical state were compared between HSIL+ and controls, and diagnostic value was determined using receiver operating characteristic analysis.
Results
Viral loads of HPV 16, 18, and 58 were significantly different in lesions in the same pathologic grade. High type-specific total viral loads were significantly associated with HSIL+ (odds ratio [OR], 14.065, 39.472, and 7.103 for HPV 16, 18, and 58, respectively). High integrated viral load was related to HSIL+ in women with HPV 16 (OR, 8.242), and integrated state was associated with HSIL+ in women with HPV 18 (OR, 9.443). Type-specific total viral load was significantly associated with HSIL+ (area under curve, 0.914, 0.937, and 0.971 for HPV 16, 18, and 58, respectively), indicating an excellent performance in detecting HSIL+.
Conclusion
Type-specific total viral load may be a powerful diagnostic marker for HSIL+ in HPV 16–, 18–, and 58–infected HSIL+ lesions. If demonstrated in all other high-risk HPV types, this method can lead to a paradigm shift in the strategy of equivocal cytologic abnormalities.

Citations

Citations to this article as recorded by  
  • Correlation of different HPV genotype viral loads and cervical lesions: A retrospective analysis of 1585 cases
    Yilu Zhou, Jiaxin Liu, Shuai Chen, Xianzhen Xin, Mohan Xiao, Xian Qiang, Lina Zhang
    Cancer Cytopathology.2025;[Epub]     CrossRef
  • HPV vaccination status and effectiveness in Korean women with HPV16/18 infection (2010–2021): a retrospective study
    Yoo Jin Na, Oeuk Jeong, Jaehyun Seong, JeongGyu Lee, So Young Lee, Sooyoung Hur, Sangmi Ryou
    Journal of Gynecologic Oncology.2024;[Epub]     CrossRef
  • Evaluation of human papillomavirus type 16 viral load and genome physical status in Iranian women with cervical disease
    Shadi Setayeshi, Ali Hasanzadeh, Yousef Yahyapour, Ahad Alizadeh, Hossein Ghorbani, Fahimeh Nokhostin, Meghdad Bagheri, Farzin Sadeghi
    Molecular Biology Reports.2024;[Epub]     CrossRef
  • Biomarkers in the Screening and Management of Cervical Cancer
    Pallavi Punhani, Charanjeet Ahluwalia
    Journal of Colposcopy and Lower Genital Tract Pathology.2024; 2(1): 6.     CrossRef
  • Prevalence of Carcinogenic Genotypes of HPV-Infected Women in a Ten-Year Period (2014–2023) in Vojvodina, Serbia
    Natasa Nikolic, Branka Basica, Mirjana Strbac, Lidija Terzic, Aleksandra Patic, Gordana Kovacevic, Radmila Velicki, Dusan Petrovic, Aljosa Mandic, Vladimir Petrovic
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  • Increased human papillomavirus viral load is correlated to higher severity of cervical disease and poorer clinical outcome: A systematic review
    Seth‐Frerich Fobian, Xionge Mei, Johannes Crezee, Barbara C. Snoek, Renske D. M. Steenbergen, Jiafen Hu, Timo L. M. ten Hagen, Louis Vermeulen, Lukas J. A. Stalpers, Arlene L. Oei
    Journal of Medical Virology.2024;[Epub]     CrossRef
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    Xue Bai, Ya-Kun Liu, Ya-Jing Jia, Dao-Juan Li, Nai-Yi Du
    International Journal of Women's Health.2024; Volume 16: 1959.     CrossRef
  • Evaluation of Human Papilloma Virus (HPV) Genotyping and Viral Load Determination as Diagnostic Biomarkers of Cervical Cancer Risk
    Marianna Martinelli, Chiara Giubbi, Laura Saderi, Rosario Musumeci, Federica Perdoni, Biagio Eugenio Leone, Robert Fruscio, Fabio Landoni, Andrea Piana, Giovanni Sotgiu, Clementina Elvezia Cocuzza
    International Journal of Molecular Sciences.2023; 24(2): 1320.     CrossRef
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    Daming Chu, Tengteng Liu, Yuan Yao
    Frontiers in Microbiology.2023;[Epub]     CrossRef
  • Prevalence and Risk Factors for High-Risk Human Papillomavirus Infection and Cervical Disorders: Baseline Findings From an Human Papillomavirus Cohort Study
    Paula Saldaña-Rodríguez, Margarita Bahena-Román, Karina Delgado-Romero, Vicente Madrid-Marina, Kirvis Torres-Poveda
    Cancer Control.2023;[Epub]     CrossRef
  • A Review of the Application of Heterostructure Catalysts in Hydrogen Evolution Reaction
    Shizhi Dong, Yanshuai Li, Zhilong Zhao, Ruichuan Li, Jiaqi He, Jinpeng Yin, Bing Yan, Xing Zhang
    ChemistrySelect.2022;[Epub]     CrossRef
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    Jovana Prelić, Aleksandra Knežević
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    Yan Sun, Jianqun Xu, Hongya Zhou, Lina You, Yan Zhu, Shoib Baba
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    Yo Suzuki, Yuki Fukumura, Miki Asahina, Mitsuhisa Fujimaki, Shinichi Ohba, Fumihiko Matsumoto, Isao Kurahayashi, Takashi Yao, Katsuhisa Ikeda
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    Jiasi Wang, Jeannette P. Staheli, Andrew Wu, Jason E. Kreutz, Qiongzheng Hu, Jingang Wang, Thomas Schneider, Bryant S. Fujimoto, Yuling Qin, Gloria S. Yen, Bob Weng, Kara Shibley, Halia Haynes, Rachel L. Winer, Qinghua Feng, Daniel T. Chiu
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  • Viral load and high prevalence of HR-HPV52 and 58 types in black women from rural communities
    Lays Paula Bondi Volpini, Jerusa Araújo Dias, Luciana Bueno de Freitas, Maria Carmen Lopes Ferreira Silva, Angélica Espinosa Miranda, Liliana Cruz Spano
    BMC Infectious Diseases.2021;[Epub]     CrossRef
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    Ewa Małusecka, Ewa Chmielik, Rafał Suwiński, Monika Giglok, Dariusz Lange, Tomasz Rutkowski, Agnieszka M. Mazurek
    Pathology & Oncology Research.2020; 26(4): 2191.     CrossRef
  • Cervical cancer risk profiling: molecular biomarkers predicting the outcome of hrHPV infection
    Mariano A Molina, Ludovica Carosi Diatricch, Marina Castany Quintana, Willem JG Melchers, Karolina M Andralojc
    Expert Review of Molecular Diagnostics.2020; 20(11): 1099.     CrossRef
  • MicroRNA-Based Fingerprinting of Cervical Lesions and Cancer
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    Journal of Clinical Medicine.2020; 9(11): 3668.     CrossRef
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Inequalities in Awareness and Attitude towards HPV and Its Vaccine between Local and Migrant Residents Who Participated in Cervical Cancer Screening in Shenzhen, China
Wei Lin, Yueyun Wang, Zhihua Liu, Bin Chen, Shixin Yuan, Bo Wu, Lin Gong
Cancer Res Treat. 2020;52(1):207-217.   Published online July 1, 2019
DOI: https://doi.org/10.4143/crt.2019.053
AbstractAbstract PDFPubReaderePub
Purpose
A cross-sectional survey was conducted to evaluate the differences on awareness and attitude towards human papillomavirus (HPV) and its vaccine between local and migrant residents who participated in cervical cancer screening in Shenzhen, China.
Materials and Methods
A total of 9,855 females sampled from healthcare institutions in 20 street blocks through the Cervical Cancer Prevention Network were surveyed in this study by a self-administered questionnaire. Multivariate logistic regression was conducted to explore the role of the hukou and resident status in the willingness to receive HPV vaccination.
Results
Local residents had a relatively higher awareness of HPV (62.0% vs. 35.6% vs. 29.9%, p < 0.001) and its vaccine (35.3% vs. 15.4% vs. 14.8%, p < 0.001), as well as a higher willingness to receive HPV vaccination (68.5% vs. 62.5% vs. 56.2%, p < 0.001) than non-permanent residents and floating population. Except for age, education level, marital status, monthly income, having daughter(s), and heard of HPV and its vaccine, the hukou and resident status significantly associated with the willingness to receive HPV vaccination (local residents vs. floating population: odds ratio, 1.216; 95% confidence interval, 1.057 to 1.398). None significant difference on the associated factors was found between local residents and internal migrants (p for interactions > 0.05).
Conclusion
Inequalities in awareness and attitude towards HPV and its vaccine existed between local and migrant residents in Shenzhen. The hukou and resident status did impact on the willingness to receive HPV vaccination, therefore, it is critical to implement effective health education campaigns on HPV and its vaccine among internal migrants.

Citations

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    Yilma Markos Larebo, Legesse Tesfaye Elilo, Desta Erkalo Abame, Denebo Ersulo Akiso, Solomon Gebre Bawore, Abebe Alemu Anshebo, Natarajan Gopalan
    Vaccines.2022; 10(12): 1988.     CrossRef
  • Prevalence and genotype distribution of human papillomavirus among women with cervical lesions in Shenzhen city, China
    Qingfeng Mai, Xiaohan Yang, Huan Cheng, Genghang Wu, Zikun Wu
    Human Vaccines & Immunotherapeutics.2021; 17(4): 965.     CrossRef
  • Cervical Cancer Screening Rate and Willingness among Female Migrants in Shenzhen, China: Three-Year Changes in Citywide Surveys
    Wei Lin, Bin Chen, Bo Wu, Shixin Yuan, Chuyan Zhong, Weikang Huang, Haiyan Hu, Zhihua Liu, Yueyun Wang
    Cancer Research and Treatment.2021; 53(1): 212.     CrossRef
  • Inequalities in Cervical Cancer Screening Uptake Between Chinese Migrant Women and Local Women: A Cross-Sectional Study
    Hunter K. Holt, Xi Zhang, Shang-Ying Hu, Fang-Hui Zhao, Jennifer S. Smith, You-Lin Qiao
    Cancer Control.2021;[Epub]     CrossRef
  • Access to Vaccination Information and Confidence/Hesitancy towards Childhood Vaccination: A Cross-Sectional Survey in China
    Fanxing Du, Tracey Chantler, Mark R. Francis, Fiona Yueqian Sun, Xuan Zhang, Kaiyi Han, Lance Rodewald, Hongjie Yu, Shiyi Tu, Heidi Larson, Zhiyuan Hou
    Vaccines.2021; 9(3): 201.     CrossRef
  • The Impact of Video-Based Educational Interventions on Cervical Cancer, Pap Smear and HPV Vaccines
    Emmanuel Kwateng Drokow, Clement Yaw Effah, Clement Agboyibor, Evans Sasu, Cecilia Amponsem-Boateng, Gloria Selorm Akpabla, Hafiz Abdul Waqas Ahmed, Kai Sun
    Frontiers in Public Health.2021;[Epub]     CrossRef
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    Qiao Gu, Wenjie Hou, Huan Liu, Lijuan Shi, Zonghao Zhu, Wenfeng Ye, Xiaoyuan Ni
    Yonsei Medical Journal.2020; 61(5): 371.     CrossRef
  • Awareness of Cervical Cancer and Attitude Toward Human Papillomavirus and Its Vaccine Among Ghanaians
    Emmanuel Kwateng Drokow, Liu Zi, Qian Han, Clement Yaw Effah, Clement Agboyibor, Evans Sasu, Gloria Selorm Akpabla, Francis Foli, Kai Sun
    Frontiers in Oncology.2020;[Epub]     CrossRef
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Investigating Trk Protein Expression between Oropharyngeal and Non-oropharyngeal Squamous Cell Carcinoma: Clinical Implications and Possible Roles of Human Papillomavirus Infection
Yoon Ah Cho, Ji Myung Chung, Hyunmi Ryu, Eun Kyung Kim, Byoung Chul Cho, Sun Och Yoon
Cancer Res Treat. 2019;51(3):1052-1063.   Published online October 24, 2018
DOI: https://doi.org/10.4143/crt.2018.411
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The relationship between head and neck squamous cell carcinoma (HNSCC) and subtypes of tropomyosin-related kinase (Trk) has not been studied in-depth. In this study, we evaluated the expression patterns of TrkA, TrkB, and panTrk and their clinicopathological significance as well as association with p16 expression and human papilloma virus (HPV) status.
Materials and Methods
Total of 396 radically resected oropharyngeal (n=121) and non-oropharyngeal (n=275) HNSCCs were included. Immunohistochemistry for TrkA, TrkB, and panTrk was performed. In addition, p16 immunohistochemistry was performed to assess the HPV status. Using HPV-negative HNSCC cell lines, FaDu and CAL27, HPV type 16 E6/E7 gene was transfected, and then changes of TrkA and TrkB expression were analyzed.
Results
In the clinical samples of HNSCC, high expression of TrkA and panTrk were more associated with oropharyngeal and p16 positive squamous cell carcinoma (SCC). In patients with completely resected (R0-resected) oropharyngeal SCC, high TrkA expression was related to superior overall survival and recurrence-free survival (RFS). In patients with R0-resected oral cavity SCC, high panTrk was related to poor RFS. In HPV type E6/E7 gene-transfected FaDu and CAL27 cell lines, increase of TrkA expression was observed.
Conclusion
It seems that expression pattern of panTrk and TrkA differed according to anatomical sites of HNSCC and was closely related to p16 expression and patient prognosis. Trk expression should be considered in the context of anatomical site, p16 expression or HPV status and Trk subtypes.

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    Lilibeth Stephania Escoto-Vasquez, Javier Portilla-Robertson, Josué Orlando Ramírez-Jarquín, Luis Fernando Jacinto-Alemán, Alejandro Alonso-Moctezuma, Carla Monserrat Ramírez-Martínez, Osmar Alejandro Chanes-Cuevas, Fabiola Salgado-Chavarria
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Human Papillomavirus Genotype-Specific Persistence and Potential Risk Factors among Korean Women: Results from a 2-Year Follow-up Study
Cecile Ingabire, Min Kyung Lim, Young-Joo Won, Jin-Kyoung Oh
Cancer Res Treat. 2018;50(3):813-822.   Published online August 17, 2017
DOI: https://doi.org/10.4143/crt.2017.340
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
High-risk human papillomavirus (HPV) infection progression should be considered a critical factor for preventing cervical cancer, although most infections are transient and rarely persist. This study aimed to examine the specific types of HPV infections, their change patterns, and the potential risk factors among Korean women.
Materials and Methods
We included 4,588 women who visited hospitals in Busan and Suwon for cervical cancer screening, and 1,224 of thesewomen attended a 2-yearfollow-up. Infection statuswas evaluated using HPV DNA testing (Hybrid Capture 2) and genotyping testing (Linear Array). Data regarding the potential risk factors for HPV infection were collected by trained nurses using structured questionnaires.
Results
Among the 1,224 women (mean age, 47 years), 105 women (8.6%) were HPV-positive at baseline. HPV infections had been cleared among 92 women (87.6%) within 2 years. Only 13 infections (12.4%) were remained, and the 10 cases of them are high-risk HPV types including genotype 33, 45, 16, 35, and 52. Among women who were negative at baseline, the HPV incidence was 4.8%. The HPV incidence was marginally associated with having multiple sexual partners (odds ratio, 2.0; 95% confidence interval, 1.0 to 3.9), although it was not significantly associated with HPV persistence.
Conclusion
Most HPV infections (88%) among Korean women were cleared within 2 years, with only a small number of persistent infections. The persistent HPV genotypes were different in our study, compared to those from previous studies. Having multiple sexual partners was associated with acquiring a HPV infection, but not with persistence.

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  • Investigation of Human Papillomavirus (HPV) Frequency and Genotype Analysis in Cervical Samples
    Yeliz Çetinkol, Selahattin Ünlü, Melahat Gürbüz, Cengiz Demir
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    秋培 谭
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Awareness of and Attitudes toward Human Papillomavirus Vaccination among Adults in Korea: 9-Year Changes in Nationwide Surveys
Jin-Kyoung Oh, Bo Yoon Jeong, E Hwa Yun, Min Kyung Lim
Cancer Res Treat. 2018;50(2):436-444.   Published online May 10, 2017
DOI: https://doi.org/10.4143/crt.2017.174
AbstractAbstract PDFPubReaderePub
Purpose
Human papillomavirus (HPV) vaccination has been included in the National Immunization Program in Korea since 2016. We aimed to evaluate changes in the awareness of and attitudes toward HPV vaccination, among adults in Korea since the first introduction of the vaccines in 2007.
Materials and Methods
A nationwide population-based survey was conducted in 2016 for 1,200 nationally representative Korean men and women; the data obtained were compared with the data from the nationwide survey conducted in 2007.
Results
A significant increase in the awareness of HPV infection (35.8%) and vaccination (36.9%) was observed in 2016 from 13.3% and 8.6% in 2007, respectively. Willingness to be vaccinated against HPV decreased from 55.0% in 2007 to 25.8% in 2016, and the proportion of respondents expressing uncertainty increased from 28.3% in 2007 to 43.3% in 2016. Only 12.1% of men and 22.0% of women knew about the free national HPV vaccination program for girls, launched in June 2016. Younger women, with higher income level, awareness of the HPV vaccine, and perception of the seriousness of infections had a higher willingness to be vaccinated. A high education level, awareness of HPV infection and vaccination, and perception of the seriousness of infection were positively associated with the willingness of respondents to vaccinate their daughters.
Conclusion
Raising the awareness of HPV infection and vaccination with appropriate knowledge is necessary for the successful implementation of the national HPV vaccination program.

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    Ülkü Ayşe TÜRKER, Binali ÇATAK
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    Soojung Jo, Soo-Yeon Han, Connor A. Walters
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The Impact of High-Risk HPV Genotypes Other Than HPV 16/18 on the Natural Course of Abnormal Cervical Cytology: A Korean HPV Cohort Study
Kyeong A So, Mi Jung Kim, Ki-Heon Lee, In-Ho Lee, Mi Kyung Kim, Yoo Kyung Lee, Chang-Sun Hwang, Mi Seon Jeong, Mee-Kyung Kee, Chun Kang, Chi Heum Cho, Seok Mo Kim, Sung Ran Hong, Ki Tae Kim, Won-Chul Lee, Jong Sup Park, Tae Jin Kim
Cancer Res Treat. 2016;48(4):1313-1320.   Published online March 9, 2016
DOI: https://doi.org/10.4143/crt.2016.013
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study is to evaluate the impact of high-risk human papillomaviruses (HPVs) other than HPV 16/18 on the natural course of atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL).
Materials and Methods
The study population was derived from the Korean HPV cohort (2010-2014). Women aged 20 to 60 who satisfied the criteria of having both HPV infection and abnormal cervical cytology of either ASC-US or LSIL were recruited from five institutions nationwide. Enrolled patients underwent cervical cytology and HPV DNA testing every 6 months.
Results
A total of 1,158 patients were enrolled. The 10 most common HPV types were HPV 16 (12.3%), 58 (10.0%), 56 (8.8%), 53 (8.4%), 52 (7.7%), 39 (6.2%), 18 (6.0%), 51 (5.7%), 68 (5.1%), and 66 (4.6%). Among these patients, 636 women were positive for high-risk HPVs other than HPV 16 or 18, and 429 women were followed for more than 6 months. Cytology evaluations showed progression in 15.3% of women, no change in 22.6%, and regression in 62.1% of women at 12 months. In cases of HPV 58 single infection, a more highly significant progression rate, compared to other high-risk types, was observed at 6 months (relative risk [RR], 3.3; 95% confidence interval [CI], 2.04 to 5.30; p < 0.001) and 12 months (RR, 5.03; 95% CI, 2.56 to 9.91; p < 0.001).
Conclusion
HPV genotypes numbered in the 50s were frequent in Korean women with ASC-US and LSIL. HPV 58 was the second most common type, with a high progression rate of cervical cytology.

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Case Report
HPV-Related Retroperitoneal Squamous Cell Carcinoma of Unknown Primary: A Case Report
Hyun Jin Oh, Eun Hye Park, Yeong Bok Lee, Jooyeun Hu, Guk Jin Lee, Sang Hoon Chun, Mi Yeong Lee, Dae Woo Lee, Jeana Kim, Jong-Youl Jin
Cancer Res Treat. 2015;47(4):954-957.   Published online February 17, 2015
DOI: https://doi.org/10.4143/crt.2014.111
AbstractAbstract PDFPubReaderePub
A 56-year-old female was referred to our hospital due to a mass measuring 5 cm in size in the left pelvic cavity, which was found incidentally during a health examination by ultrasonography. Exploratory laparotomy was performed and the mass was located at the left retroperitoneal parametrium without invasion of the uterus and ovary. The pathology report confirmed squamous cell carcinoma. Even after further studies, we did not find any other primary lesion. Human papillomavirus (HPV) DNA chip test (HPV 9G DNA Membrane Kit, Biometrixtechnology Inc.) showed that the surgical specimen was positive for HPV 18. She received adjuvant chemotherapy and would receive radiation therapy for the possibility of occult gynecologic cancer. Retroperitoneal squamous cell carcinoma of unknown primary is extremely rare and little is known about it. It is reported that HPV may be associated with the disease. Hence, the result of HPV test could have an impact on finding a suspicious primary lesion and treatment modality in this case.

Citations

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  • A case of pelvic squamous cell carcinoma of unknown primary origin that responded well to radiotherapy and nivolumab
    Hiroaki Koge, Ayako Hino, Akira Kakiuchi, Yayoi Yamamoto, Akira Kanbe, Daichi Kojima, Ayumi Horikawa, Tsunehiro Doiuchi, Hiroaki Kurihara
    Radiology Case Reports.2024; 19(5): 1881.     CrossRef
  • HPV-related metastatic retroperitoneal pelvic squamous cell carcinoma of unknown primary origin in a patient previously treated for endometrial cancer
    Olga P. Matylevich, Mikalay A. Kurchankou, Pavel A. Kopsсhaj, Kathleen M. Schmeler
    International Journal of Surgery Case Reports.2024; 118: 109624.     CrossRef
  • Case report: HPV related pelvic retroperitoneal squamous cell cancer of unknown primary presenting as ovary neoplasm
    Hui Yan, Shao-dan Lin
    International Journal of Surgery Case Reports.2024; 125: 110528.     CrossRef
  • Primary retroperitoneal squamous cell carcinoma: a literature review
    Ankita Pandey, Divyesh Kumar, Parikshaa Gupta, Divya Khosla, Kannan Periasamy, Rakesh Kapoor
    Journal of Cancer Research and Clinical Oncology.2023; 149(13): 12507.     CrossRef
  • A case of synchronous high‐grade cervical intraepithelial neoplasia and metastatic squamous cell carcinomas of unknown primary in rectum
    Syunsuke Orisaka, Mitsuhiro Nakamura, Takeshi Obata, Junpei Iwadare, Yasunari Mizumoto, Hiroshi Fujiwara
    Journal of Obstetrics and Gynaecology Research.2021; 47(7): 2555.     CrossRef
  • Primary retroperitoneal squamous cell carcinoma: a case report with review of the literature
    Yu Matsuzaka, Ken Yamaguchi, Koki Moriyoshi, Yumi Takao, Kenji Takakura, Ikuo Konishi
    International Cancer Conference Journal.2019; 8(2): 61.     CrossRef
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    Elie El Rassy, Joseph Kattan, Nicholas Pavlidis
    European Journal of Clinical Investigation.2019;[Epub]     CrossRef
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    Amir Isbell, Emma C. Fields
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Original Articles
The Increasing Frequency of Cervical Cancer in Korean Women under 35
Chan Hee Han, Hyun Jung Cho, Sung Jong Lee, Jeong Hoon Bae, Seog Nyen Bae, Sung Eun Namkoong, Jong Sup Park
Cancer Res Treat. 2008;40(1):1-5.   Published online March 31, 2008
DOI: https://doi.org/10.4143/crt.2008.40.1.1
AbstractAbstract PDFPubReaderePub
Purpose

The goal of this study was to determine the clinical and epidemiological trends of cervical cancer in young Korean women. Social behavior including sexual habits has changed in Korean women, with sexual activity commencing at a younger age. These changes are likely to influence certain risk factors of cervical cancer, resulting in changing trends in the occurrence of the disease.

Materials and Methods

The incidence of cervical cancer in women less than 35 years-old between January 1990 and December 2006 was analyzed, and available medical records from January 1996 to December 2006 were reviewed. The clinical, pathological and epidemiologic characteristics and changing trends among these young patients were analyzed.

Results

Over the last two decades, the incidence of young (< 35 years) cervical cancer patients increased, more patients had an aggressive form of the disease, and there was a higher rate of women with more advanced education. Human papillomavirus (HPV) infection was detected in 94.0% of the women (63/67) tested. HPV 16 (82.5%) and HPV 18 (12.7%) were the two most common viral infections detected throughout the study period.

Conclusions

The changing trends and risk factors identified suggest a need for more active education of young women about cervical cancer prevention strategies. In addition, young women are strongly recommended to undergo a regular screening test and HPV vaccination.

Citations

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  • Prevalence and Treatment of Vulvar Cancer From 2014−2018: A Nationwide Population-Based Study in Korea
    Yung-Taek Ouh, Dongwoo Kang, Hoseob Kim, Jae Kwan Lee, Jin Hwa Hong
    Journal of Korean Medical Science.2022;[Epub]     CrossRef
  • Successful Treatment of Synchronous Double Lung Primary Malignancies and Colon Cancer
    Hosam A Alghanmi
    Cureus.2022;[Epub]     CrossRef
  • WITHDRAWN: Polymerase chain reaction technique for molecular detection of HPV16 infections among women with cervical cancer in Dhi-Qar Province
    Abduladheem Turki Jalil, Ali Hussein Demin Al-Khafaji, Aleksandr Karevskiy, Saja Hussain Dilfy, Zaman K. Hanan
    Materials Today: Proceedings.2021;[Epub]     CrossRef
  • Current Status of Human Papillomavirus Infection and Introduction of Vaccination to the National Immunization Program in Korea: an Overview
    Min-A Kim, Gwan Hee Han, Jae-Hoon Kim, Kyung Seo
    Journal of Korean Medical Science.2018;[Epub]     CrossRef
  • Management for locally advanced cervical cancer: new trends and controversial issues
    Oyeon Cho, Mison Chun
    Radiation Oncology Journal.2018; 36(4): 254.     CrossRef
  • Trends and Age-Period-Cohort Effects on the Incidence and Mortality Rate of Cervical Cancer in Korea
    Eun-Kyeong Moon, Chang-Mo Oh, Young-Joo Won, Jong-Keun Lee, Kyu-Won Jung, Hyunsoon Cho, Jae Kwan Jun, Myong Cheol Lim, Moran Ki
    Cancer Research and Treatment.2017; 49(2): 526.     CrossRef
  • Factors associated with participation in cervical cancer screening among young Koreans: a nationwide cross-sectional study
    Ha Kyun Chang, Jun-Pyo Myong, Seung Won Byun, Sung-Jong Lee, Yong Seok Lee, Hae-Nam Lee, Keun Ho Lee, Dong Choon Park, Chan Joo Kim, Soo Young Hur, Jong Sup Park, Tae Chul Park
    BMJ Open.2017; 7(4): e013868.     CrossRef
  • Molecular Detection and Typing of Human Papillomaviruses in Paraffin-Embedded Cervical Cancer and Pre-Cancer Tissue Specimens
    Pezhman Mahmoodi, Hossein Motamedi, Masoud Reza Seyfi Abad Shapouri, Mahjabin Bahrami Shehni, Mohammad Kargar
    Iranian Journal of Cancer Prevention.2016;[Epub]     CrossRef
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    F. Ben Khaial, Z. Bodalal, A. Elramli, F. Elkhwsky, A. Eltaguri, R. Bendardaf
    Journal of Obstetrics and Gynaecology.2014; 34(6): 523.     CrossRef
  • Current status of the National Cancer Screening Program for cervical cancer in Korea, 2009
    Young Hwa Lee, Kui Son Choi, Hoo-Yeon Lee, Jae Kwan Jun
    Journal of Gynecologic Oncology.2012; 23(1): 16.     CrossRef
  • Laparoscopic versus open radical hysterectomy in early-stage cervical cancer: long-term survival outcomes in a matched cohort study
    J.-H. Nam, J.-Y. Park, D.-Y. Kim, J.-H. Kim, Y.-M. Kim, Y.-T. Kim
    Annals of Oncology.2012; 23(4): 903.     CrossRef
  • The safety of conization in the management of adenocarcinomain situof the uterine cervix
    Mi-La Kim, Ho-Suap Hahn, Kyung-Taek Lim, Ki-Heon Lee, Hy-Sook Kim, Sung-Ran Hong, Tae-Jin Kim
    Journal of Gynecologic Oncology.2011; 22(1): 25.     CrossRef
  • Human papillomavirus 16/18 AS04-adjuvanted cervical cancer vaccine: immunogenicity and safety in 15-25 years old healthy Korean women
    Seung Cheol Kim, Yong Sang Song, Young-Tae Kim, Young Tak Kim, Ki-Sung Ryu, Bhavyashree Gunapalaiah, Dan Bi, Hans L Bock, Jong-Sup Park
    Journal of Gynecologic Oncology.2011; 22(2): 67.     CrossRef
  • Prognostic value of metabolic tumor volume measured by FDG-PET/CT in patients with cervical cancer
    Hyun Hoon Chung, Jae Weon Kim, Kyung Hee Han, Jae Seon Eo, Keon Wook Kang, Noh-Hyun Park, Yong-Sang Song, June-Key Chung, Soon-Beom Kang
    Gynecologic Oncology.2011; 120(2): 270.     CrossRef
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Hydrogen Peroxide Producing Lactobacilli in Women with Cervical Neoplasia
Ho Sun Choi, Ki Min Kim, Chol Hong Kim, Seok Mo Kim, Jong Seok Oh
Cancer Res Treat. 2006;38(2):108-111.   Published online April 30, 2006
DOI: https://doi.org/10.4143/crt.2006.38.2.108
AbstractAbstract PDFPubReaderePub
Purpose

It is well known that human papillomavirus (HPV) is the main cause of cervical neoplasia, and hydrogen peroxide-producing lactobacilli are the most important microorganisms for maintaining the balance of the vaginal ecosystem. The purpose of our study was to investigate the relationship of hydrogen peroxide-producing lactobacilli, cervical neoplasia and high-risk HPV.

Materials and Methods

We enrolled 1138 women with abnormal cervical smears or cervicograms who were referred to the department of Obstetrics and Gynecology at Chonnam National University Medical School. In all of them, 1,138 vaginal swabs were collected for the qualitative assay of hydrogen peroxide producing lactobacilli and 150 cervical swabs were used for the HPV hybrid capture II test without regard to the subjects' pregnancy status. In the non-pregnant women, 880 cervical biopsies and/or loop electrosurgical excision procedures were performed for making the histological diagnosis.

Results

There was no significant difference not only between the distribution of H2O2 producing lactobacilli and the cervical histology, but also between the distribution of H2O2 producing lactobacilli and the positivity for high-risk HPV.

Conclusions

Both cervical neoplasia and high-risk HPV may not be influenced by the existence of hydrogen peroxide producing lactobacilli in the vagina.

Citations

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  • Unravelling the Biological Interplay Between Genital HPV Infection and Cervicovaginal Microbiota in Sub-Saharan Africa: Implications for Cervical (Pre)cancer Prevention
    Harris Onywera, Zizipho Z. A. Mbulawa, Adrian Brink, Anna-Lise Williamson, Lamech M. Mwapagha
    Venereology.2024; 3(4): 211.     CrossRef
  • Antimicrobial activity of Lactobacillus against microbial flora of cervicovaginal infections
    Subramanyam Dasari, Raju Naidu Devanaboyaina Shouri, Rajendra Wudayagiri, Lokanatha Valluru
    Asian Pacific Journal of Tropical Disease.2014; 4(1): 18.     CrossRef
  • PCR‐based identification of eight lactobacillus species and 18 hr‐HPV genotypes in fixed cervical samples of south african women at risk of HIV and BV
    Joke A.M. Dols, Gregor Reid, Remco Kort, Frank H.J. Schuren, Hugo Tempelman, Tj. Romke Bontekoe, Hans Korporaal, E.M. Van der Veer, Pieter W. Smit, Mathilde E. Boon
    Diagnostic Cytopathology.2012; 40(6): 472.     CrossRef
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Accelerated Induction of Dysplastic Lesion by TPA in HPV18 URR E6/E7 Gene Expressing Transgenic Mice
Yongil Kwon, Taechul Park, Jongsup Park, Soojong Um, Jauheung Yu, Junmo Lee, Seungeun Namkoong
J Korean Cancer Assoc. 2001;33(1):56-63.
AbstractAbstract PDF
PURPOSE
The research of HPV has been severely hampered by the inability to propagate HPVs in culture, particularly those of the mucosotrophic types which produce few virions in vivo. In order to study the regulation of HPV-18 expression in vivo, we constructed transgenic mice and caused cervical neoplasia.
MATERIALS AND METHODS
We investigated whether tetradecanoyl phorbol acetate (TPA) increase the transcriptional activity of the URR in the C33A cervical carcinoma cells or not. And we asked whether chronic exposure of female HPV-18 URR E6/E7 transgenic mice to TPA could render the reproductive tract squamous epithelium permissive for HPV neoplasia.
RESULTS
It was confirmed by RT-PCR that transgene was specifically expressed in epithelial tissues. TPAupregulated the transcriptional activity of the URR in the C33A cervical carcinoma cells. There were diffuse changes on the squamous epithelium in the cervix of the transgenic mice at fifth month following TPA treatment.
CONCLUSION
We established the transgenic mice model which have the ability to reproduce the development of cervical dysplasias. Moreover this animal model will allow preclinical testing of compounds designed to interfere with the actions of the HPV oncogenes or other critical aspects of the cancer phenotype.
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The Effects of Interferon/Retinoic Acid on Cervical Cancer Cell Lines According to the Mutational Status of HPV-URR
Tae Yeon Kim, Chan Joo Kim, Eun Joo Kim, Tae Chul Park, Sung Eun Namkoong, Jae Gahb Park, Soo Jong Um, Jong Sup Park
J Korean Cancer Assoc. 2000;32(5):884-894.
AbstractAbstract PDF
PURPOSE
We investigated the effects of all-trans-retinoic acid (ATRA) and/or interferon-gamma (IFN-gamma) on the growth of various cervical cancer cell lines and HPV E6/E7 expression. The relationships between the functional activities of HPV-URR and the growth inhibition were identified.
MATERIALS AND METHODS
Four groups of cell lines were included; i) with integrated form of HPV-16 DNA (SNU-17, CaSki), ii) episomal form of HPV-16 (SNU-523), iii) integrated form of HPV-18 (SNU-1160, HeLa) and iv) episomal form of HPV-18 (SNU-1245). The promoter activity of HPV-URR was confirmed by transient transfection assay in C33A using the HPV-18 URR-CAT reporter plasmid.
RESULTS
Selective mutation was detected in TEF-1 (transcriptional enhancer factor) binding site in SNU-17, and the activity of URR in SNU-17 was higher than that of the prototype. The proliferation was more inhibited in SNU-17 by IFN-gamma (10 ng/ml) than in SNU-902, CaSki and HeLa. The increase of the HPV-URR activity might play a role in the inhibition of growth by interferon-g. The expression of HPV-16 E6/E7 were significantly decreased by ATRA or IFN-gamma.
CONCLUSION
Point mutation at TEF-1 binding site of SNU-17 was related with the increased transcriptional activity of URR. Mutation in the HPV-URR and alteration of HPV-URR activity in SNU-17 might be related with significant growth suppression by IFN-gamma.
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Polymorphisms in E6 Gene of Human Papillomavirus Type 16 Found in Cervical Tissues from Korean Women
Jae Weon Kim, Ju Won Roh, Moon Hong Kim, Noh Hyun Park, Yong Sang Song, Soon Beom Kang, Hyo Pyo Lee
J Korean Cancer Assoc. 2000;32(5):875-883.
AbstractAbstract PDF
PURPOSE
To examine the distribution of HPV 16 E6 polymorphisms and analyse the possible association between the polymorphisms and cervical cancer development in Korean women.
MATERIALS AND METHODS
Fifty-four cases of uterine cervical tissues containing HPV 16 DNA confirmed by polymerase chain reaction (PCR) from Korean women were subjected to investigate the E6 gene mutations. PCR-amplified products were sequenced by the fluorescent dideoxy ter mination method and the results obtained from sequencing were analysed. And newly designed PASA method was tried to develop rapid test for identification of the most commonly detected variation.
RESULTS
Among the 27 cervical cancer cases, only two (7.4%) was found as a prototype. Among 11 kind of variants identified in total, 4 variants (5 nucleotide sites) which were never reported before has been found, registered firstly to GenBank. The most frequently found variation was D25E, absolutely different from the previous reports from the western country. There was no statistically significant trend for the D25E variation to be more frequently detected in cancerous lesions than in noncancerous lesions. All of the DNA sequencing results observed could be confirmed by PASA method.
CONCLUSION
These results suggest that Korean-specific genetic factors might operate during the cervical carcinogenesis.
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Relationship of HPV Detection and p53 Expression in Urinary Bladder Cancer
Keun Hong Kee, Hyang Mee Shin, Young Chul Kim
J Korean Cancer Assoc. 2000;32(1):129-135.
AbstractAbstract PDF
PURPOSE
The purpose of this study was to investigate the relationship between aberrant p53 expression and the presence of human papillomavirus DNA in transitional cell carcinomas of the urinary bladder.
MATERIALS AND METHODS
This study analyzed 30 paraffin-embedded transitional cell carcinoma of the urinary bladder, including 10 cases of grade I, 10 cases of grade II, and 10 cases of grade III, for the presence of DNA-HPV and abnormal accumulation of p53. We used immunohistochemical staining for p53 protein and in situ hybridization for HPV DNA, respectively.
RESULTS
Overall positive rate of HPV DNA type 16 and type 18 was 60.0% and 53.3%, respectively. Nuclear accumulation of p53 was found in 13 cases (43.3%) of all transitional cell carcinomas. In HPV DNA type 16 positive cases, the p53 was positive in 8 cases and negative in 10 cases. In HPV DNA type 16 negative cases, the p53 was positive in 5 cases and negative in 7 cases. In HPV DNA type 18 positive cases, the p53 was positive in 7 cases and negative in 9 cases. In HPV DNA type 16 negative cases, the p53 was positive in 6 cases and negative in 8 cases.
CONCLUSION
This results suggest that HPV infection and p53 gene accumulation may contribute to the significant role in the carcinogenesis of the utinary bladder. In additon, HPV infection and p53 accumulation may be related to tumor progression and higher grade.
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Detection of Human Papillomavirus DNA and p53 , p21 Gene Expression in CIN3 and Uterine Cervical Cancer
Jae Hyung Na, Ho Sun Choi
J Korean Cancer Assoc. 2000;32(1):100-109.
AbstractAbstract PDF
PURPOSE
Though the etiology of this cancer has not been elucidated, it has been suggested that certain types of human papillomavirus (HPV) and alteration of the p53 gene are closely associated with uterine cervical cancer. The aim of the study was to investigate the role of high risk HPV, p53 and p21 gene in cervical intraepithelial neoplasia III (CIN3) and invasive squamous cell carcinoma.
MATERIALS AND METHODS
The presence of high-risk HPV DNA (16, 18, 31, 33, 35, 45, 51, 52, 56) were detected from cervical swab in 240 patients by hybrid capture method. Expression of p53 genes were studied in paraffin-embedded specimens by immunohisto- chemical staining and p53, p21 gene alteration by RT-PCR SSCP using fresh cervical tissues.
RESULTS
High risk HPV DNA were detected in 34%, 74.3% and 75.7% in control, CIN3 and invasive squamaus cell carcinoma respectively. In patients with high risk HPV DNA, type 16 were detected of 5.9%, 30.8%, 47.2% respectively. Relative concentration of HPV DNA to control was 16.3+-27.4 in CIN3 and 30.4+-40.8 in invasive squamous cell cancer. Of patients with high risk HPV DNA, p53 expression was found in 42.9% of CIN3 immunohistochemically, while patients with invasive squamous cell carcinoma was de- tected in 50%. In patients without high risk HPV DNA, p53 expression was detected in 17.1% in CIN3, 15.7% in invasive squamous cell carcinoma. But the mutation of p53 and p21 gene by RT-PCR SSCP were not observed in CIN3 and invasive squamous cell carcinoma.
CONCLUSION
These observations suggest that carcinogenesis of invasive squamous cell carcinoma from CIN3 may be concerned with high risk HPV concentration and may be occurred via another pathway without HPV and p53 or p21 mutation.
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Integration of HPV and the Antibody Respones to HPV Proteins in Patients with Cervical Cancer
Joon Mo Lee, Seung Jo Kim, Jong Sup Park, Sung Eun Namkoong, Chan Joo Kim, Tae Chul Park, Soo Jong Um
J Korean Cancer Assoc. 1998;30(6):1184-1197.
AbstractAbstract PDF
PURPOSE
HPV (human papillomavirus) are known as the major causative agent for development of cervical cancer. High-risk HPVs, especially HPV-16 /18 DNA, are often found to be integrated into the human genome in high grade CINs as well as cervial cancer. Investigation of the relationship between the genomic states of HPV genes and their antibody response against the HPV-16 Ll/L2 virus-like particles (VLPs) and the in vitro translated E6 and E7 proteins may help to explain the mechanism of HPV-related cervical carcinogenesis and host immune responses.
MATERIALS AND METHODS
Cervical cancer tissues obtained from 41 patients with cervical cancer were studied by PCR, Southern blot hybridization and the antibody response against HPV-16 Ll/L2 VLPs and HPV-16 E6, E7 proteins of serum were tested by ELISA and radioimmunoprecipitation assay (RIPA), respectively.
RESULTS
Integrated forms of the HPV-16 DNA were found in 23 of the 38 patients (60.5%). The HPV-16 positive cervial cancer patients had a significantly higher prevalence (39.5%; 15/38) of antibodies to HPV-16 Ll/L2 VLPs than 8.7% (2/28) of the the control group (p<0.05). Antibodies to HPV-16 Ll/L2 VLPs were more detectable in 60% (9/15) of the cervical cancer patients with episomal forms of HPV-16 DNA than those who having only integrated HPV-16 (26.1%; 6/23) (p<0.05). Antibodies to E6 and E7 proteins were positive in 36.8% (14/38) and 50% (19/38) of the patients with HPV-16 positive cervical cancer. And those were siginificantly higher than the positivities for the control group (8.3% and 2.8%), (p<0.05). The difference between seroreactivities to E6 and E7 proteins in the patients with episomal forms of HPV-16 DNA (pure episomal and mixed forms) and those with integrated froms of HPV-16 DNA was not significant (P>0.05). CONCLUSION: Integrated forms of HPV-16 DNA were prevalent in most patients with cervical cancer. Antibodies to HPV-16 Ll/L2 VLPs, in vitro translated HPV-16 E6 and E7 proteins appeared in the significantly larger proportions of the HPV-associated cervical cancer patients than in the controls. Antibodies to HPV-16 Ll/L2 VLPs were more detectable in the cervical cancer patients with episomal form of HPV-16 DNA than those who having only integrated forms of HPV-16. Antibody responses to HPV-16 E6 and E7 proteins were not influenced by the different viral states. More numbers of studies would be necessary to determine the relationship between the genomic states of HPV and the immune responses to their proteins by the such genomic and serologic parameters.
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Expression of p53 and MHC Class I According to HPV Infection in Laryngeal Squamous Cell Carcinomas
Chan Seung Hwang, Hoon Kim, Mi Kyung Kim
J Korean Cancer Assoc. 1998;30(1):1-11.
AbstractAbstract PDF
PURPOSE
We evaluated the HPV type 16, 18 infection and p53 expression and MHC class Iantigen expression, and analyzed he relationship between HPV infection and p53 expression and MHC class I expression in laryngeal squamous cell carcinomas.
MATERIALS AND METHODS
Thirty-nine cases of laryngeal squamous cell carcinomas and ten cases of laryngeal nodules were analyzed for detection of HPV DNA by in situ hybridization and the detection of p53 and MHC class I antigen by immunohistochemical technique.
RESULTS
HPV DNA was detected in 10(26%), and p53 expression was detected in 19(49%) out of 39 cases in laryngeal squamous cell carcinomas. HPV positive cases showed 50% of p53 expression whereas HPV negative cases showed 48% expression. MHC class I down-regulation (heterogenous and negative expression) in HPV positive lesions was higher than HPV negative lesions, but there was no statistically significance. The expression of MHC class I was related to cellular differentiation regardless of T-stage and nodal involvement.
CONCLUSION
There was no reiationship between HPV infection and p53 expression and MHC class I expression in laryngeal squamous cell carcinomas. Also these results suggest that MHC class I expression can make it possible to presume indirectly the malignant potentiality of the tumor.
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A Study on the Loss of Heterozygosity of the p53 Gene in Primary Uterine Cervical Carcinomas
Jin Woo Kim, Chun Geun Lee, Yeo Won Sohn, Hong Ki Min, Su Mi Han, Eun Young Cho, Kyung Sook Kim, Joon Mo Lee, Sung Eun Namkoong
J Korean Cancer Assoc. 1997;29(2):280-290.
AbstractAbstract PDF
PURPOSE
Allelic deletion of p53 tumor suppressor gene have been observed frequently in a variety of human tumors. These losses are believed to contribute to the development of human cancers. But the loss of heterozygosity (LOH) data on chromosome 17p are rare and controversial with respect to cervical carcinomas. So, we tried to elucidate the frequency of p53 locus LOH in primary cervical carcinoma and compared the LOH data with clinicopathological parameters.
MATERIALS AND METHODS
In order to detect LOH within one of the well-known tumor suppressor gene, p53, three intragenic polymorphisms (exon 1, exon 4, and intron 6) and one microsatellite distal to the p53 gene (D17S5) were examined. Paired DNA samples from 55 primary uterine cervical carcinomas and normal bloods were studied for the chromosomal allelic loss of p53 gene locus by polymerase chain reaction (PCR), the presence of human papilloma virus (HPV), and the presence of p53 gene point mutation by PCR-single conformation polymorphism (SSCP) analysis. And the relationships between allelic losses of this gene and conventional clinicopathological parameters were evaluated.
RESULTS
We could increase the heterozygosity of the p53 gene up to 1 (100%). The observed allelic loss rate of the p53 locus in informative cases was 5.5% (3/55) and the observed allelic loss rate of the D17S5 locus in informative cases was 8.7% (4/46) . Only one of the four patients with LOH at the D17S5 locus showed a concomittant allelic loss of the p53 gene. The overall LOH incidence of the chromosomal region comprising 17p13.1 (p53) to 17p13.3 (D13S5) was 10.9% (6/55). All the samples contained at least one of the oncogenic HPV type 16 and/or 18 sequences. No shifted bands were observed in the PCR-SSCP analysis of the p53 gene. The LOH of the p53 gene was not related to other parameters including clinical stage, histological type, and degree of differentiation.
CONCLUSION
Concerning with the results above, we conclude that the allelic imbalance of the p53 gene itself is not implicated as a major contributing factor in the malignant transformation or the tumor progression in HPV-positive cervical cancers. Another putative tumor suppressor gene which has more important function than p53 gene in cervical carcinogenesis might exist between these two loci [p53 (17p13.1) and D17S5 (17p13.3)].
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The Assessment of Proliferation cell Uncear Antigen ( PCNA ) in Cervical Carcinoma Patients Infected with Human Papillomavirus types 16 and 18
Soo Nyung Kim, Tchan Kyu Park, Ho Gune Kim, Kyung Sup Kim
J Korean Cancer Assoc. 1995;27(5):773-783.
AbstractAbstract PDF
Proliferating cell nuciear antigen (PCNA) is a nuclear protein sssociated with the cell prolif- erative state. The relationship between the presence of human papillomavirus (HPV) and proliferative indices (PI) was studied. Determination of PI was done by immunohistochemical staining via the avidin-biotin-complex immunoperoxidase method and HPV 16 and HPV 18 status by Southern blot hybridization on paraffin-embedded material from 49 patients with carcinoma of the uterine cervix. HPV 16 was present in 15 cases, HPV 18 wes observed in 6 cases, and both HPV 16 and HPV 18 were found in 4 cases. There was significant correlation between PI and HPV types. PI was 59.7+-9.0% in HPV 16 positive lesion, 67.4+-10.6% in HPV 18 positive lesion, 79.4+-4.2% in both HPV 16 and HPV 18 positive lesion, and 57.5+-16.9% in HPV negative lesion. Among cervical adenocarcinomas, PI was 72.5+-5 14.9% in HPV l6 or HPV 18 positive lesion, as compared to 39.8+-15.1% in HPV negative leaion. No correlation was found between HPV-DNA positivity and PI in relation to clinical stages, histologic typea, and lesion size.
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The Association of p53 Mutation with Human Papillomavirus Type 16 , 18 Infection and its Clinical Significance
Chang Soo Park, Yong Sang Song, Chang Won Koh, Hye Won Jeon, Soon Beom Kang, Hyo Pyo Lee
J Korean Cancer Assoc. 1996;28(1):122-138.
AbstractAbstract PDF
Recent several studies have suggested that inactivation of p53 gene could occur by two theoretical mechanisms in cervical cancer. The E6 transforming protein of oncogenic human papillomavirus(HPV) binds to and promotes the degradation of p53 protein, or the mutation of the p53 gene could result in its inactivation without HPV infection. The purpose of this study were to investigate HPV infection and p53 mutation according to the status of lymph node metastasis and to analyse the relationship and role of HPV infection and p53 alteration in the advance and metastasis of cervical cancer. Paraffin embedded tissue sections were obtained from 30 patients with cervical cancer, each l5 patients with or without lymph node metastasis. The PCR and Southern blotting were used for the detection of HPV l6/18 DNA. Alteration of p53 activity was evaluated by immunohistochemistry using MAb DO7 and polymerase chain reaction with single stranded conformation polymorphism(PCR-SSCP). There was no significant difference in HPV infection between two groups, 73.3%(l l/15) in negative lymph node group and 80.0%(l2/15) in positive lymph node group. Although by immunohistochemistry p53 alterations were found more frequently in positive lymph node group(46.7%) than in negative lymph node group(20.0%), there was no significant difference between two groups. HPV negative cervical cancers had more p53 alterations(57.l%) than HPV positive cervical cancers(26.1%). However, there was no significant inverse relationship between HPV infection and p53 alteration. In conclusion, these data suggest that HPV infection and p53 alteration may play an important role independantly in the development of cervical cancer and p53 alteration may be associated with the advance and metastasis in some cases.
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