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Clinicopathologic characterization of cervical metastasis from an unknown primary tumor: a multicenter study in Korea
Miseon Lee, Uiree Jo, Joon Seon Song, Youn Soo Lee, Chang Gok Woo, Dong-Hoon Kim, Jung Yeon Kim, Sun Och Yoon, Kyung-Ja Cho
J Pathol Transl Med. 2023;57(3):166-177.   Published online May 10, 2023
DOI: https://doi.org/10.4132/jptm.2023.04.12
  • 1,998 View
  • 128 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDFSupplementary Material
Background
Research regarding cervical metastasis from an unknown primary tumor (CUP) according to human papillomavirus (HPV) and Epstein-Barr virus (EBV) status in Korea has been sporadic and small-scale. This study aims to analyze and understand the characteristics of CUP in Korea according to viral and p16 and p53 status through a multicenter study.
Methods
Ninety-five cases of CUP retrieved from six hospitals in Korea between January 2006 and December 2016 were subjected to high-risk HPV detection (DNA in situ hybridization [ISH] or real-time polymerase chain reaction), EBV detection (ISH), and immunohistochemistry for p16 and p53.
Results
CUP was HPV-related in 37 cases (38.9%), EBV-related in five cases (5.3%), and unrelated to HPV or EBV in 46 cases (48.4%). HPV-related CUP cases had the best overall survival (OS) (p = .004). According to the multivariate analysis, virus-unrelated disease (p = .023) and longer smoking duration (p < .005) were prognostic factors for poor OS. Cystic change (p = .016) and basaloid pattern (p < .001) were more frequent in HPV-related cases, and lymphoepithelial lesion was frequent in EBV-related cases (p = .010). There was no significant association between viral status and p53 positivity (p = .341), smoking status (p = .728), or smoking duration (p = .187). Korean data differ from Western data in the absence of an association among HPV, p53 positivity, and smoking history.
Conclusions
Virus-unrelated CUP in Korea had the highest frequency among all CUP cases. HPV-related CUP is similar to HPV-mediated oropharyngeal cancer and EBVrelated CUP is similar to nasopharyngeal cancer in terms of characteristics, respectively.

Citations

Citations to this article as recorded by  
  • Expansion of tumor-infiltrating lymphocytes from head and neck squamous cell carcinoma to assess the potential of adoptive cell therapy
    Sangjoon Choi, Mofazzal Hossain, Hyun Lee, Jina Baek, Hye Seon Park, Chae-Lyul Lim, DoYeon Han, Taehyun Park, Jong Hyeok Kim, Gyungyub Gong, Mi-Na Kweon, Hee Jin Lee
    Cancer Immunology, Immunotherapy.2024;[Epub]     CrossRef
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Evaluation of human papillomavirus (HPV) prediction using the International Endocervical Adenocarcinoma Criteria and Classification system, compared to p16 immunohistochemistry and HPV RNA in-situ hybridization
Hezhen Ren, Jennifer Pors, Christine Chow, Monica Ta, Simona Stolnicu, Robert Soslow, David Huntsman, Lynn Hoang
J Pathol Transl Med. 2020;54(6):480-488.   Published online August 31, 2020
DOI: https://doi.org/10.4132/jptm.2020.07.18
  • 4,886 View
  • 162 Download
  • 8 Web of Science
  • 8 Crossref
AbstractAbstract PDF
Background
The International Endocervical Adenocarcinoma Criteria and Classification (IECC) separated endocervical adenocarcinomas into human papillomavirus (HPV) associated (HPVA) and non–HPV-associated (NHPVA) categories by morphology alone. Our primary objective was to assess the accuracy of HPV prediction by the IECC system compared to p16 immunohistochemistry and HPV RNA in-situ hybridization (RISH). Our secondary goal was to directly compare p16 and HPV RISH concordance.
Methods
Cases were classified by IECC and stained for p16 and HPV RISH on tissue microarray, with discordant p16/HPV RISH cases re-stained on whole tissue sections. Remaining discordant cases (p16/HPV, IECC/p16, IECC/HPV discordances) were re-reviewed by the original pathologists (n = 3) and external expert pathologists (n = 2) blinded to the p16 and HPV RISH results. Final IECC diagnosis was assigned upon independent agreement between all reviewers.
Results
One hundred and eleven endocervical adenocarcinomas were classified originally into 94 HPVA and 17 NHPVA cases. p16 and HPV RISH was concordant in 108/111 cases (97%) independent of the IECC. HPV RISH and p16 was concordant with IECC in 103/111 (93%) and 106/111 (95%), respectively. After expert review, concordance improved to 107/111 (96%) for HPV RISH. After review of the eight discordant cases, one remained as HPVA, four were reclassified to NHPVA from HPVA, two were unclassifiable, and one possibly represented a mixed usual and gastric-type adenocarcinoma.
Conclusions
p16 and HPV RISH have excellent concordance in endocervical adenocarcinomas, and IECC can predict HPV status in most cases. Focal apical mitoses and apoptotic debris on original review led to the misclassification of several NHPVA as HPVA.

Citations

Citations to this article as recorded by  
  • Joint detection of multiple HPV-testing technologies and evaluation of clinicopathological characteristics discriminate between HPV-independent and low-copy HPV-associated cervical squamous cell carcinoma (CSCC) -an analysis of 3869 cases
    Linghui Lu, Tianqi Liu, Shunni Wang, Jing Li, Feiran Zhang, Yan Ning, Yiqin Wang
    Gynecologic Oncology.2023; 170: 59.     CrossRef
  • Incidence and Clinicopathologic Characteristics of Human Papillomavirus–independent Invasive Squamous Cell Carcinomas of the Cervix
    Simona Stolnicu, Douglas Allison, Aaron M. Praiss, Basile Tessier-Cloutier, Amir Momeni Boroujeni, Jessica Flynn, Alexia Iasonos, Rene Serrette, Lien Hoang, Andrei Patrichi, Cristina Terinte, Anna Pesci, Claudia Mateoiu, Ricardo R. Lastra, Takako Kiyokawa
    American Journal of Surgical Pathology.2023; 47(12): 1376.     CrossRef
  • Testing Algorithms for the Diagnosis of Malignant Glandular Tumors of the Uterine Cervix Histotyped per the International Endocervical Adenocarcinoma Criteria and Classification (IECC) System
    Máire A. Duggan, Qiuli Duan, Ruth M. Pfeiffer, Mary Anne Brett, Sandra Lee, Mustapha Abubakar, Martin Köbel, Monica Rodriguez, Aylin Sar
    Applied Immunohistochemistry & Molecular Morphology.2022; 30(2): 91.     CrossRef
  • Local and Metastatic Relapses in a Young Woman with Papillary Squamous Cell Carcinoma of the Uterine Cervix
    Ha Young Woo, Hyun-Soo Kim
    Diagnostics.2022; 12(3): 599.     CrossRef
  • Clinical correlation of lymphovascular invasion and Silva pattern of invasion in early-stage endocervical adenocarcinoma: proposed binary Silva classification system
    Simona Stolnicu, Lien Hoang, Noorah Almadani, Louise De Brot, Glauco Baiocchi, Graziele Bovolim, Maria Jose Brito, Georgia Karpathiou, Antonio Ieni, Esther Guerra, Takako Kiyokawa, Pavel Dundr, Carlos Parra-Herran, Sofia Lérias, Ana Felix, Andres Roma, An
    Pathology.2022; 54(5): 548.     CrossRef
  • Reproducibility of Morphologic Parameters of the International Endocervical Adenocarcinoma Criteria and Classification System and Correlation With Clinicopathologic Parameters: A Multi-Institutional Study
    Pinar Bulutay, Nihan Haberal, Özlem Özen, Özlem Erdem, Emine H. Zeren, İbrahim Kulac, Çagatay Taskiran, Dogan Vatansever, Ali Ayhan, Nilgün Kapucuoğlu
    International Journal of Gynecological Pathology.2022; 41(5): 447.     CrossRef
  • HPV-Negative Cervical Cancer: A Narrative Review
    Francesca Arezzo, Gennaro Cormio, Vera Loizzi, Gerardo Cazzato, Viviana Cataldo, Claudio Lombardi, Giuseppe Ingravallo, Leonardo Resta, Ettore Cicinelli
    Diagnostics.2021; 11(6): 952.     CrossRef
  • International Endocervical Adenocarcinoma Criteria and Classification (IECC): An Independent Cohort With Clinical and Molecular Findings
    Hezhen Ren, Noorah Almadani, Jennifer Pors, Samuel Leung, Julie Ho, Christine Chow, Monica Ta, Kay J. Park, Simona Stolnicu, Robert Soslow, David Huntsman, Blake C. Gilks, Lynn Hoang
    International Journal of Gynecological Pathology.2021; 40(6): 533.     CrossRef
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Prevalence of high-risk human papillomavirus and its genotype distribution in head and neck squamous cell carcinomas
Yuil Kim, Young-Hoon Joo, Min-Sik Kim, Youn Soo Lee
J Pathol Transl Med. 2020;54(5):411-418.   Published online July 21, 2020
DOI: https://doi.org/10.4132/jptm.2020.06.22
  • 6,893 View
  • 172 Download
  • 18 Web of Science
  • 21 Crossref
AbstractAbstract PDF
Background
High-risk (HR) human papillomavirus (HPV) is found in a subset of head and neck (HN) squamous cell carcinomas (SCCs). For oropharyngeal SCCs, HR HPV positivity is known to be associated with good prognosis, and a separate staging system for HPV-associated carcinomas using p16 immunohistochemistry (IHC) as a surrogate test has been adopted in the 8th American Joint Committee on Cancer staging system. We examined the HR HPV status and the genotype distribution in five HN subsites.
Methods
Formalin-fixed paraffin-embedded tissue sections were used for p16 IHC and DNA extraction. HPV DNA detection and genotyping were done employing either a DNA chip-based or real-time polymerase chain reaction–based method.
Results
During 2011–2019, a total of 466 SCCs were tested for HPV DNA with 34.1% positivity for HR HPV. Among HN subsites, the oropharynx showed the highest HR HPV prevalence (149/205, 75.1%), followed by the sinonasal tract (3/14, 21.4%), larynx (5/43, 11.6%), hypopharynx (1/38, 2.6%), and oral cavity (1/166, 0.6%). The most common HPV genotype was HPV16 (84.3%) followed by HPV35 (6.9%) and HPV33 (4.4%). Compared with HR HPV status, the sensitivity and specificity of p16 IHC were 98.6% and 94.3% for the oropharynx, and 99.2% and 93.8% for the tonsil, respectively.
Conclusions
Using a Korean dataset, we confirmed that HR HPV is most frequently detected in oropharyngeal SCCs. p16 positivity showed a good concordance with HR HPV DNA for oropharyngeal and especially tonsillar carcinomas. The use of p16 IHC may further be extended to predict HR HPV positivity in sinonasal tract SCCs.

Citations

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  • Risk factors for cervical lymph node metastasis in oropharyngeal cancer and its impact on prognosis
    Li Zhang, Zhilin Li, Jing Wang, Chen Wang, Shuxin Wen
    Brazilian Journal of Otorhinolaryngology.2025; 91(2): 101520.     CrossRef
  • Characteristics of human papillomavirus infection among oropharyngeal cancer patients: A systematic review and meta-analysis
    Meimei Cui, Jinling Cheng, Huijuan Cheng, Ming Zhao, Dan Zhou, Min Zhang, Jingjing Jia, Limei Luo
    Archives of Oral Biology.2024; 157: 105830.     CrossRef
  • Impact of histopathological parameters in prognosis of oral squamous cell carcinoma
    R. P. Ekanayaka, W. M. Tilakaratne
    Oral Diseases.2024;[Epub]     CrossRef
  • Longitudinal Screening for Oral High-Risk Non-HPV16 and Non-HPV18 Strains of Human Papillomavirus Reveals Increasing Prevalence among Adult and Pediatric Biorepository Samples: A Pilot Study
    Jordan Jacobs, Eugene Chon, Karl Kingsley
    Vaccines.2024; 12(8): 895.     CrossRef
  • Position Statement about Gender-Neutral HPV Vaccination in Korea
    Kyung-Jin Min, Yung-Taek Ouh, Sangrak Bae, Yong-Bae Ji, Jae-Kwan Lee, Jae-Weon Kim, Kwang-Jae Cho, Dong-Hun Im
    Vaccines.2024; 12(10): 1110.     CrossRef
  • Prevalence of human papilloma virus in head and neck mucous squamous cell carcinoma and genotypes by location: an observational study
    Emilie Uhlrich, Jerzy Klijanienko, Joey Martin, Emmanuelle Jeannot, Anne Vincent-Salomon, Paul Freneaux, Christophe Le Tourneau, Olivier Choussy, Antoine Dubray-Vautrin
    European Journal of Cancer Prevention.2024;[Epub]     CrossRef
  • High-risk HPV Does not Appear to be an Important Risk Factor for Sinonasal Carcinomas in Turkish Population: A Tertiary Center Experience
    Evsen Apaydin Arikan, Levent Aydemir, Murat Ulusan, Dilek Yilmazbayhan, Yasemin Ozluk
    International Journal of Surgical Pathology.2023; 31(2): 124.     CrossRef
  • Practical Application of Circulating Tumor-Related DNA of Human Papillomavirus in Liquid Biopsy to Evaluate the Molecular Response in Patients with Oropharyngeal Cancer
    Agnieszka M. Mazurek, Tomasz W. Rutkowski
    Cancers.2023; 15(4): 1047.     CrossRef
  • The Prevalence of HPV in Oral Cavity Squamous Cell Carcinoma
    Seyed Keybud Katirachi, Mathias Peter Grønlund, Kathrine Kronberg Jakobsen, Christian Grønhøj, Christian von Buchwald
    Viruses.2023; 15(2): 451.     CrossRef
  • The Protective Role of Cranberries and Blueberries in Oral Cancer
    César Esquivel-Chirino, Mario Augusto Bolaños-Carrillo, Daniela Carmona-Ruiz, Ambar Lopéz-Macay, Fernando Hernández-Sánchez, Delina Montés-Sánchez, Montserrat Escuadra-Landeros, Luis Alberto Gaitán-Cepeda, Silvia Maldonado-Frías, Beatriz Raquel Yáñez-Ocam
    Plants.2023; 12(12): 2330.     CrossRef
  • Unusual cases of sinonasal malignancies: a letter to the editor on HPV-positive sinonasal squamous cell carcinomas
    Benedicte Bitsch Lauritzen, Sannia Sjöstedt, Jakob Myllerup Jensen, Katalin Kiss, Christian von Buchwald
    Acta Oncologica.2023; 62(6): 608.     CrossRef
  • Prevalence of human Papillomavirus associated oropharyngeal and oral squamous cell carcinoma in Asian countries: A systematic review and large-scale meta-analysis
    Yy Jean Tan, Ken Wong Siong Hou, Galvin Sim Siang Lin, Jasmine Lim Suk Wun, Wan Nor Amira Wan Ahmad Abdul Nasir, Lynn Wei Linn Ko
    Acta Marisiensis - Seria Medica.2023; 69(2): 77.     CrossRef
  • Top 100 most cited articles on human papillomavirus-induced head and neck squamous cell carcinoma: A bibliographic review
    Rahul Mohandas, Subhashree Mohapatra, Mary Oshin, ShubhangiSambhaji Hajare
    Journal of International Oral Health.2023; 15(3): 219.     CrossRef
  • Intracellular Toll-Like Receptors Modulate Adaptive Immune Responses in Head and Neck Cancer
    Sangeetha K. Nayanar, Deepak Roshan V.G., Shruthi Surendran, Göran Kjeller, Bengt Hasséus, Daniel Giglio
    Viral Immunology.2023; 36(10): 659.     CrossRef
  • Positive Rate of Human Papillomavirus and Its Trend in Head and Neck Cancer in South Korea
    Hyun Woong Jun, Yong Bae Ji, Chang Myeon Song, Jae Kyung Myung, Hae Jin Park, Kyung Tae
    Frontiers in Surgery.2022;[Epub]     CrossRef
  • Transcriptionally active HPV in OPMD and OSCC: A systematic review following the CAP/ASCO guidelines
    Laura Borges Kirschnick, Lauren Frenzel Schuch, Maria Eduarda Pérez‐de‐Oliveira, Ana Gabriela Costa Normando, Bruno Augusto Linhares Almeida Mariz, Eliete Neves Silva Guerra, Felipe Martins Silveira, Ana Carolina Uchoa Vasconcelos, Luciana Estevam Simonat
    Oral Diseases.2022; 28(8): 2309.     CrossRef
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    Chan Woo Wee, Hyo-Jung Lee, Jae-Ryun Lee, Hyejin Lee, Min-Jeong Kwoen, Woo-Jin Jeong, Keun-Yong Eom
    Cancer Research and Treatment.2022; 54(3): 709.     CrossRef
  • Expression of p16, p53, and TLR9 in HPV-Associated Head and Neck Squamous Cell Carcinoma: Clinicopathological Correlations and Potential Prognostic Significance
    Shu Wang, Xibing Zhuang, Caixia Gao, Tiankui Qiao
    OncoTargets and Therapy.2021; Volume 14: 867.     CrossRef
  • The Role of Human Papilloma Virus in Dictating Outcomes in Head and Neck Squamous Cell Carcinoma
    Shane Brennan, Anne-Marie Baird, Esther O’Regan, Orla Sheils
    Frontiers in Molecular Biosciences.2021;[Epub]     CrossRef
  • A Contemporary Systematic Review on Repartition of HPV-Positivity in Oropharyngeal Cancer Worldwide
    Amanda F. Carlander, Kathrine K. Jakobsen, Simone K. Bendtsen, Martin Garset-Zamani, Charlotte D. Lynggaard, Jakob Schmidt Jensen, Christian Grønhøj, Christian von Buchwald
    Viruses.2021; 13(7): 1326.     CrossRef
  • The Prevalence of High- and Low-Risk Types of HPV in Patients with Squamous Cell Carcinoma of the Head and Neck, Patients with Chronic Tonsillitis, and Healthy Individuals Living in Poland
    Joanna Katarzyna Strzelczyk, Krzysztof Biernacki, Jadwiga Gaździcka, Elżbieta Chełmecka, Katarzyna Miśkiewicz-Orczyk, Natalia Zięba, Janusz Strzelczyk, Maciej Misiołek
    Diagnostics.2021; 11(12): 2180.     CrossRef
Article image
Gene variant profiles and tumor metabolic activity as measured by FOXM1 expression and glucose uptake in lung adenocarcinoma
Ashley Goodman, Waqas Mahmud, Lela Buckingham
J Pathol Transl Med. 2020;54(3):237-245.   Published online March 4, 2020
DOI: https://doi.org/10.4132/jptm.2020.02.08
  • 5,128 View
  • 119 Download
  • 2 Web of Science
  • 1 Crossref
AbstractAbstract PDF
Background
Cancer cells displaying aberrant metabolism switch energy production from oxidative phosphorylation to glycolysis. Measure of glucose standardized uptake value (SUV) by positron emission tomography (PET), used for staging of adenocarcinoma in high-risk patients, can reflect cellular use of the glycolysis pathway. The transcription factor, FOXM1 plays a role in regulation of glycolytic genes. Cancer cell transformation is driven by mutations in tumor suppressor genes such as TP53 and STK11 and oncogenes such as KRAS and EGFR. In this study, SUV and FOXM1 gene expression were compared in the background of selected cancer gene mutations.
Methods
Archival tumor tissue from cases of lung adenocarcinoma were analyzed. SUV was collected from patient records. FOXM1 gene expression was assessed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Gene mutations were detected by allele-specific PCR and gene sequencing.
Results
SUV and FOXM1 gene expression patterns differed in the presence of single and coexisting gene mutations. Gene mutations affected SUV and FOXM1 differently. EGFR mutations were found in tumors with lower FOXM1 expression but did not affect SUV. Tumors with TP53 mutations had increased SUV (p = .029). FOXM1 expression was significantly higher in tumors with STK11 mutations alone (p < .001) and in combination with KRAS or TP53 mutations (p < .001 and p = .002, respectively).
Conclusions
Cancer gene mutations may affect tumor metabolic activity. These observations support consideration of tumor cell metabolic state in the presence of gene mutations for optimal prognosis and treatment strategy.

Citations

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  • Prognostic value of combining clinical factors, 18F-FDG PET-based intensity, volumetric features, and deep learning predictor in patients with EGFR-mutated lung adenocarcinoma undergoing targeted therapies: a cross-scanner and temporal validation study
    Kun-Han Lue, Yu-Hung Chen, Sung-Chao Chu, Chih-Bin Lin, Tso-Fu Wang, Shu-Hsin Liu
    Annals of Nuclear Medicine.2024; 38(8): 647.     CrossRef
Article image
Colorectal epithelial neoplasm associated with gut-associated lymphoid tissue
Yo Han Jeon, Ji Hyun Ahn, Hee Kyung Chang
J Pathol Transl Med. 2020;54(2):135-145.   Published online January 29, 2020
DOI: https://doi.org/10.4132/jptm.2019.11.06
  • 6,583 View
  • 233 Download
AbstractAbstract PDF
Background
Colorectal epithelial neoplasm extending into the submucosal gut-associated lymphoid tissue (GALT) can cause difficulties in the differential diagnosis. Regarding GALT-associated epithelial neoplasms, a few studies favor the term “GALT carcinoma” while other studies have mentioned the term “GALT-associated pseudoinvasion/epithelial misplacement (PEM)”.
Methods
The clinicopathologic characteristics of 11 cases of colorectal epithelial neoplasm associated with submucosal GALT diagnosed via endoscopic submucosal dissection were studied.
Results
Eight cases (72.7%) were in males. The median age was 59 years, and age ranged from 53 to 73. All cases had a submucosal tumor component more compatible with GALT-associated PEM. Eight cases (72.7%) were located in the right colon. Ten cases (90.9%) had a non-protruding endoscopic appearance. Nine cases (81.8%) showed continuity between the submucosal and surface adenomatous components. Nine cases showed (81.8%) focal defects or discontinuation of the muscularis mucosae adjacent to the submucosal GALT. No case showed hemosiderin deposits in the submucosa or desmoplastic reaction. No case showed single tumor cells or small clusters of tumor cells in the submucosal GALT. Seven cases (63.6%) showed goblet cells in the submucosa. No cases showed oncocytic columnar cells lining submucosal glands.
Conclusions
Our experience suggests that pathologists should be aware of the differential diagnosis of GALT-associated submucosal extension by colorectal adenomatous neoplasm. Further studies are needed to validate classification of GALT-associated epithelial neoplasms.
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Comparison of papanicolaou smear and human papillomavirus (HPV) test as cervical screening tools: can we rely on HPV test alone as a screening method? An 11-year retrospective experience at a single institution
Myunghee Kang, Seung Yeon Ha, Hyun Yee Cho, Dong Hae Chung, Na Rae Kim, Jungsuk An, Sangho Lee, Jae Yeon Seok, Juhyeon Jeong
J Pathol Transl Med. 2020;54(1):112-118.   Published online January 15, 2020
DOI: https://doi.org/10.4132/jptm.2019.11.29
  • 8,519 View
  • 238 Download
  • 13 Web of Science
  • 14 Crossref
AbstractAbstract PDF
Background
The decrease in incidence of cervical dysplasia and carcinoma has not been as dramatic as expected with the development of improved research tools and test methods. The human papillomavirus (HPV) test alone has been suggested for screening in some countries. The National Cancer Screening Project in Korea has applied Papanicolaou smears (Pap smears) as the screening method for cervical dysplasia and carcinoma. We evaluated the value of Pap smear and HPV testing as diagnostic screening tools in a single institution.
Methods
Patients co-tested with HPV test and Pap smear simultaneously or within one month of each other were included in this study. Patients with only punch biopsy results were excluded because of sampling errors. A total of 999 cases were included, and the collected reports encompassed results of smear cytology, HPV subtypes, and histologic examinations.
Results
Sensitivity and specificity of detecting high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC) were higher for Pap smears than for HPV tests (sensitivity, 97.14%; specificity, 85.58% for Pap smears; sensitivity, 88.32%; specificity, 54.92% for HPV tests). HPV tests and Pap smears did not differ greatly in detection of low-grade squamous intraepithelial lesion (85.35% for HPV test, 80.31% for Pap smears). When atypical glandular cells were noted on Pap smears, the likelihood for histologic diagnosis of adenocarcinoma following Pap smear was higher than that of high-risk HPV test results (18.8 and 1.53, respectively).
Conclusions
Pap smears were more useful than HPV tests in the diagnosis of HSIL, SCC, and glandular lesions.

Citations

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    E Chen, Hua-Nong Ting, Joon Huang Chuah, Jun Zhao
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    T. Stverakova, I. Baranova, P. Mikyskova, B. Gajdosova, H. Vosmikova, J. Laco, V. Palicka, H. Parova
    Frontiers in Oncology.2023;[Epub]     CrossRef
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    Nurhan Doğan, Gamze Fışkın
    Journal of Obstetrics and Gynaecology Research.2022; 48(6): 1433.     CrossRef
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    Dan Hou, Binjie Yang, Yangdan Li, Ming Sun
    Frontiers in Public Health.2022;[Epub]     CrossRef
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    Bernardo Vega Crespo, Vivian Alejandra Neira, José Ortíz S, Ruth Maldonado-Rengel, Diana López, Andrea Gómez, María José Vicuña, Jorge Mejía, Ina Benoy, Tesifón Parrón Carreño, Veronique Verhoeven
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  • Diagnostic distribution and pitfalls of glandular abnormalities in cervical cytology: a 25-year single-center study
    Jung-A Sung, Ilias P. Nikas, Haeryoung Kim, Han Suk Ryu, Cheol Lee
    Journal of Pathology and Translational Medicine.2022; 56(6): 354.     CrossRef
  • Primary screening of cervical cancer by Pap smear in women of reproductive age group
    Ruchi Mishra, Dakshina Bisht, Manisha Gupta
    Journal of Family Medicine and Primary Care.2022; 11(9): 5327.     CrossRef
  • Comparison of Learning Transfer Using Simulation Problem-Based Learning and Demonstration: An Application of Papanicolaou Smear Nursing Education
    Jeongim Lee, Hae Kyoung Son
    International Journal of Environmental Research and Public Health.2021; 18(4): 1765.     CrossRef
  • Investigating host-virus interaction mechanism and phylogenetic analysis of viral proteins involved in the pathogenesis
    Ahmad Abu Turab Naqvi, Farah Anjum, Alaa Shafie, Sufian Badar, Abdelbaset Mohamed Elasbali, Dharmendra Kumar Yadav, Md. Imtaiyaz Hassan, Timir Tripathi
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Article image
Analysis of the molecular subtypes of preoperative core needle biopsy and surgical specimens in invasive breast cancer
Ye Sul Jeong, Jun Kang, Jieun Lee, Tae-Kyung Yoo, Sung Hun Kim, Ahwon Lee
J Pathol Transl Med. 2020;54(1):87-94.   Published online November 13, 2019
DOI: https://doi.org/10.4132/jptm.2019.10.14
  • 6,735 View
  • 203 Download
  • 15 Web of Science
  • 17 Crossref
AbstractAbstract PDF
Background
Accurate molecular classification of breast core needle biopsy (CNB) tissue is important for determining neoadjuvant systemic therapies for invasive breast cancer. The researchers aimed to evaluate the concordance rate (CR) of molecular subtypes between CNBs and surgical specimens.
Methods
This study was conducted with invasive breast cancer patients who underwent surgery after CNB at Seoul St. Mary’s Hospital between December 2014 and December 2017. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 were analyzed using immunohistochemistry. ER and PR were evaluated by Allred score (0–8). HER2 was graded from 0 to +3, and all 2+ cases were reflex tested with silver in situ hybridization. The labeling index of Ki67 was counted by either manual scoring or digital image analysis. Molecular subtypes were classified using the above surrogate markers.
Results
In total, 629 patients were evaluated. The CRs of ER, PR, HER2, and Ki67 were 96.5% (kappa, 0.883; p<.001), 93.0% (kappa, 0.824; p<.001), 99.7% (kappa, 0.988; p<.001), and 78.7% (kappa, 0.577; p<.001), respectively. Digital image analysis of Ki67 in CNB showed better concordance with Ki67 in surgical specimens (CR, 82.3%; kappa, 0.639 for digital image analysis vs. CR, 76.2%; kappa, 0.534 for manual counting). The CRs of luminal A, luminal B, HER2, and triple negative types were 89.0%, 70.0%, 82.9%, and 77.2%, respectively.
Conclusions
CNB was reasonably accurate for determining ER, PR, HER2, Ki67, and molecular subtypes. Using digital image analysis for Ki67 in CNB produced more accurate molecular classifications.

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Review
Current Status of and Perspectives on Cervical Cancer Screening in Korea
Sung-Chul Lim, Chong Woo Yoo
J Pathol Transl Med. 2019;53(4):210-216.   Published online May 16, 2019
DOI: https://doi.org/10.4132/jptm.2019.04.11
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AbstractAbstract PDF
Since the introduction of the Papanicolaou (Pap) smear system in 1943, cervicovaginal cytology has been used as a standard screening test for cervical cancer. The dissemination of this test contributed to reductions of the incidence and mortality of cervical cancer worldwide. In Korea, regular health check-ups for industrial workers and their family members were introduced in 1988 and were performed as part of the National Cancer Screening Program in 1999. As a result, the incidence of cervical cancer in Korea has been steadily decreasing. However, about 800 cases of cervical cancer-related deaths are reported each year due to false-negative test results. Hence, new screening methods have been proposed. Liquid-based cytology (LBC) was introduced in 1996 to overcome the limitations of conventional Pap smears. Since then, other LBC methods have been developed and utilized, including the human papilloma virus test—a method with higher sensitivity that requires fewer screenings. In this study, we review current issues and future perspectives related to cervical cancer screening in Korea.

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    Ka Yu Tse, Kimio Ushijima, Ai Ling Tan, Perapong Intasorn, Jitendra Pariyar, Chih‐Long Chang, Efren J. Domingo, Hiralal Konar, Suresh Kumarasamy, Brahmana Askandar Tjokroprawiro, Sarikapan Wilailak
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Original Article
Human Leukocyte Antigen Class I and Programmed Death-Ligand 1 Coexpression Is an Independent Poor Prognostic Factor in Adenocarcinoma of the Lung
Yeon Bi Han, Hyun Jung Kwon, Soo Young Park, Eun-Sun Kim, Hyojin Kim, Jin-Haeng Chung
J Pathol Transl Med. 2019;53(2):86-93.   Published online January 14, 2019
DOI: https://doi.org/10.4132/jptm.2018.12.26
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AbstractAbstract PDF
Background
Both human leukocyte antigen (HLA) class I and programmed death-ligand 1 (PD-L1) molecules are known to play important roles in cancer immunity. In this study, we evaluated HLA class I expression in resected adenocarcinoma of the lung, and investigated its prognostic impact in correlation with PD-L1 expression.
Methods
HLA class I and PD-L1 expression was evaluated by immunohistochemistry in a total of 403 resected lung adenocarcinomas using tissue microarray. Correlations between the expression of HLA class I/PD-L1 and clinicopathologic features and prognostic significance were analyzed.
Results
HLA class I expression was reduced in 91.6% of adenocarcinoma, and more frequently reduced in patients with younger age, absence of vascular invasion, and low pathologic stage (p = .033, p = .007, and p = .012, respectively). Positive PD-L1 expression in tumor cells was 16.1% (1% cut-off), and associated with poor differentiation, presence of vascular invasion and nodal metastasis (p < .001, p = .002, and p = .032, respectively). On survival analysis, HLA class I or PD-L1 expression alone did not show any statistical significance. On the integrated analysis, HLA class I (+)/PD-L1 (+) subgroup showed a significantly shorter overall survival than other groups (p = .001). Multivariate analysis revealed that coexpression of HLA class I and PD-L1 was an independent poor prognostic factor of lung adenocarcinoma. (p < .001; hazard ratio, 6.106; 95% confidence interval, 2.260 to 16.501).
Conclusions
Lung adenocarcinoma with coexpression of HLA class I and PD-L1 was associated with poor prognosis. This subgroup may evade immune attack by expressing PD-L1 protein despite HLA expression.

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  • Assessment of cancer cell‐expressed HLA class I molecules and their immunopathological implications
    Terufumi Kubo, Shiori Asano, Kenta Sasaki, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Yoshihiko Hirohashi, Toshihiko Torigoe
    HLA.2024;[Epub]     CrossRef
  • Prognostic and Clinical Significance of Human Leukocyte Antigen Class I Expression in Breast Cancer: A Meta-Analysis
    Weiqiang Qiao, Zhiqiang Jia, Wanying Guo, Qipeng Liu, Xiao Guo, Miao Deng
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    Ioannis M. Koukourakis, Alexandra Giatromanolaki, Achilleas Mitrakas, Michael I. Koukourakis
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Review
Let Archived Paraffin Blocks Be Utilized for Research with Waiver of Informed Consent
Yong-Jin Kim, Jeong Sik Park, Karam Ko, Chang Rok Jeong
J Pathol Transl Med. 2018;52(3):141-147.   Published online April 5, 2018
DOI: https://doi.org/10.4132/jptm.2018.02.07
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AbstractAbstract PDF
Advances in biomedical and genetic research have contributed to more effective public health improvement via bench-to-bed research and the emergence of personalized medicine. This has certainly showcased the importance of archived human tissues, especially paraffin-embedded blocks in pathology. Currently in Korea, undue legislative regulations of the Bioethics and Safety Act suspend and at times discourage studies from taking place. In this paper, the authors underline the value of paraffin blocks in the era of personalized and translational medicine. We discuss detailed clauses regarding the applicability of paraffin blocks from a legal perspective and compare Korea’s regulations with those of other countries. The necessity for allowing waived consent and Institutional Review Board (IRB) approval will be argued throughout. The authors suggest that researchers declare the following to obtain IRB approval and waiver of informed consents: research could not be practically carried out without a waiver of consent; the proposed research presents no more than minimal risk of harm to subjects, and the waiver of consent will not adversely affect the rights and welfare of subjects; and research will not utilize a tissue block if only 1 is available for each subject, to allow future clinical use such as re-evaluation or further studies.

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  • NaV1.7 channels are expressed in the lower airways of the human respiratory tract
    Everardo Hernández-Plata, Ana Alfaro Cruz, Carina Becerril
    Respiratory Physiology & Neurobiology.2023; 311: 104034.     CrossRef
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    Mahmood S. Mozaffari, Rafik Abdelsayed
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    Yong-Jin Kim, Chang Rok Jeong, Jeong Sik Park
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Original Articles
The Smad4/PTEN Expression Pattern Predicts Clinical Outcomes in Colorectal Adenocarcinoma
Yumin Chung, Young Chan Wi, Yeseul Kim, Seong Sik Bang, Jung-Ho Yang, Kiseok Jang, Kyueng-Whan Min, Seung Sam Paik
J Pathol Transl Med. 2018;52(1):37-44.   Published online October 23, 2017
DOI: https://doi.org/10.4132/jptm.2017.10.20
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AbstractAbstract PDFSupplementary Material
Background
Smad4 and PTEN are prognostic indicators for various tumor types. Smad4 regulates tumor suppression, whereas PTEN inhibits cell proliferation. We analyzed and compared the performance of Smad4 and PTEN for predicting the prognosis of patients with colorectal adenocarcinoma.
Methods
Combined expression patterns based on Smad4+/– and PTEN+/– status were evaluated by immunostaining using a tissue microarray of colorectal adenocarcinoma. The relationships between the protein expression and clinicopathological variables were analyzed.
Results
Smad4–/PTEN– status was most frequently observed in metastatic adenocarcinoma, followed by primary adenocarcinoma and tubular adenoma (p<.001). When Smad4–/PTEN– and Smad4+/PTEN+ groups were compared, Smad4–/PTEN– status was associated with high N stage (p=.018) and defective mismatch repair proteins (p=.006). Significant differences in diseasefree survival and overall survival were observed among the three groups (Smad4+/PTEN+, Smad4–/PTEN+ or Smad4+/PTEN–, and Smad4–/PTEN–) (all p<.05).
Conclusions
Concurrent loss of Smad4 and PTEN may lead to more aggressive disease and poor prognosis in patients with colorectal adenocarcinoma compared to the loss of Smad4 or PTEN alone.

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  • Association between the expression of epithelial–mesenchymal transition (EMT)-related markers and oncologic outcomes of colorectal cancer
    Mona Hany Emile, Sameh Hany Emile, Amr Awad El-Karef, Mohamed Awad Ebrahim, Ibrahim Eldosoky Mohammed, Dina Abdallah Ibrahim
    Updates in Surgery.2024;[Epub]     CrossRef
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    Michela Roberto, Giulia Arrivi, Emanuela Pilozzi, Andrea Montori, Genoveffa Balducci, Paolo Mercantini, Andrea Laghi, Debora Ierinò, Martina Panebianco, Daniele Marinelli, Silverio Tomao, Paolo Marchetti, Federica Mazzuca
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    Ion Cristóbal, Blanca Torrejón, Andrea Santos, Melani Luque, Marta Sanz-Alvarez, Federico Rojo, Jesús García-Foncillas
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Implication of PHF2 Expression in Clear Cell Renal Cell Carcinoma
Cheol Lee, Bohyun Kim, Boram Song, Kyung Chul Moon
J Pathol Transl Med. 2017;51(4):359-364.   Published online June 13, 2017
DOI: https://doi.org/10.4132/jptm.2017.03.16
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AbstractAbstract PDF
Background
Clear cell renal cell carcinoma (CCRCC) is presumed to be associated with adipogenic differentiation. Histone modification is known to be important for adipogenesis, and the function of histone demethylase plant homeodomain finger 2 (PHF2) has been noted. In addition, PHF2 may act as a tumor suppressor via epigenetic regulation of p53 and is reported to be reduced in colon cancer and stomach cancer tissues. In this study, we examined PHF2 expression in CCRCC specimens by immunohistochemistry.
Methods
We studied 254 CCRCCs and 56 non-neoplastic renal tissues from patients who underwent radical or partial nephrectomy between 2000 and 2003 at the Seoul National University Hospital. Tissue microarray blocks were prepared, and immunohistochemical staining for PHF2 was performed.
Results
Among 254 CCRCC cases, 150 cases (59.1%) showed high expression and 104 cases (40.1%) showed low expression. High expression of PHF2 was significantly correlated with a low Fuhrman nuclear grade (p < .001), smaller tumor size (p < .001), low overall stage (p = .003), longer cancer-specific survival (p = .002), and progression-free survival (p < .001) of the patients. However, it was not an independent prognostic factor in multivariate analysis adjusted for Fuhrman nuclear grade and overall stage.
Conclusions
Our study showed that low expression of PHF2 is associated with aggressiveness and poor prognosis of CCRCC.

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    Ignacio Alonso-de Vega, Maria Cristina Paz-Cabrera, Magdalena B Rother, Wouter W Wiegant, Cintia Checa-Rodríguez, Juan Ramón Hernández-Fernaud, Pablo Huertas, Raimundo Freire, Haico van Attikum, Veronique A J Smits
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    Sarder Arifuzzaman, Mst Reshma Khatun, Rabeya Khatun
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    Stella Pappa, Natalia Padilla, Simona Iacobucci, Marta Vicioso, Elena Álvarez de la Campa, Claudia Navarro, Elia Marcos, Xavier de la Cruz, Marian A. Martínez-Balbás
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    Zheng Ge, Yan Gu, Qi Han, Justin Sloane, Qinyu Ge, Goufeng Gao, Jinlong Ma, Huihui Song, Jiaojiao Hu, Baoan Chen, Sinisa Dovat, Chunhua Song
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Case Study
Perivascular Epithelioid Cell Tumor in the Stomach
Sun Ah Shin, Jiwoon Choi, Kyung Chul Moon, Woo Ho Kim
J Pathol Transl Med. 2017;51(4):428-432.   Published online April 4, 2017
DOI: https://doi.org/10.4132/jptm.2016.09.16
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AbstractAbstract PDF
Perivascular epithelioid cell tumors or PEComas can arise in any location in the body. However, a limited number of cases of gastric PEComa have been reported. We present two cases of gastric PEComas. The first case involved a 62-year-old woman who presented with a 4.2 cm gastric subepithelial mass in the prepyloric antrum, and the second case involved a 67-year-old man with a 5.0 cm mass slightly below the gastroesophageal junction. Microscopic examination revealed that both tumors were composed of perivascular epithelioid cells that were immunoreactive for melanocytic and smooth muscle markers. Prior to surgery, the clinical impression of both tumors was gastrointestinal stromal tumor (GIST), and the second case was erroneously diagnosed as GIST even after microscopic examination. Although gastric PEComa is a very rare neoplasm, it should be considered in the differential diagnosis of gastric submucosal lesions.

Citations

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  • Unusual paediatric sigmoid perivascular epithelioid cell tumour with regional lymph node metastasis treated using gemcitabine and docetaxel: a case report and literature review
    Hsiu-Chung Cheng, Chia-Yu Kuo, Ching-Wen Huang, Hsiang-Hung Shih, Chih-Hung Lin, Jaw-Yuan Wang
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  • Gastric Perivascular Epithelioid Cell Tumor (PEComa)
    Jinghong Xu, Yu Yan, Xueping Xiang, Peter Jiang, Xiangrong Hu, Wenjun Yang
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  • Robotic wedge resection of a rare gastric perivascular epithelioid cell tumor: A case report
    Alessandra Marano, Francesca Maione, Yanghee Woo, Luca Pellegrino, Paolo Geretto, Diego Sasia, Mirella Fortunato, Giulio Fraternali Orcioni, Roberto Priotto, Renato Fasoli, Felice Borghi
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Original Articles
Detection of Human Papillomavirus in Korean Breast Cancer Patients by Real-Time Polymerase Chain Reaction and Meta-Analysis of Human Papillomavirus and Breast Cancer
Jinhyuk Choi, Chungyeul Kim, Hye Seung Lee, Yoo Jin Choi, Ha Yeon Kim, Jinhwan Lee, Hyeyoon Chang, Aeree Kim
J Pathol Transl Med. 2016;50(6):442-450.   Published online October 10, 2016
DOI: https://doi.org/10.4132/jptm.2016.07.08
  • 11,732 View
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AbstractAbstract PDF
Background
Human papillomavirus (HPV) is a well-established oncogenic virus of cervical, anogenital, and oropharyngeal cancer. Various subtypes of HPV have been detected in 0% to 60% of breast cancers. The roles of HPV in the carcinogenesis of breast cancer remain controversial. This study was performed to determine the prevalence of HPV-positive breast cancer in Korean patients and to evaluate the possibility of carcinogenic effect of HPV on breast.
Methods
Meta-analysis was performed in 22 case-control studies for HPV infection in breast cancer. A total of 123 breast cancers, nine intraductal papillomas and 13 nipple tissues of patients with proven cervical HPV infection were tested by real-time polymerase chain reaction to detect 28 subtypes of HPV. Breast cancers were composed of 106 formalin-fixed and paraffin embedded (FFPE) breast cancer samples and 17 touch imprint cytology samples of breast cancers.
Results
The overall odds ratio between breast cancer and HPV infection was 5.43 (95% confidence interval, 3.24 to 9.12) with I2 = 34.5% in meta-analysis of published studies with case-control setting and it was statistically significant. HPV was detected in 22 cases of breast cancers (17.9%) and two cases of intaductal papillomas (22.2%). However, these cases had weak positivity.
Conclusions
These results failed to serve as significant evidence to support the relationship between HPV and breast cancer. Further study with larger epidemiologic population is merited to determine the relationship between HPV and breast cancer.

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Clinical Significance of an HPV DNA Chip Test with Emphasis on HPV-16 and/or HPV-18 Detection in Korean Gynecological Patients
Min-Kyung Yeo, Ahwon Lee, Soo Young Hur, Jong Sup Park
J Pathol Transl Med. 2016;50(4):294-299.   Published online June 26, 2016
DOI: https://doi.org/10.4132/jptm.2016.05.09
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AbstractAbstract PDF
Background
Human papillomavirus (HPV) is a major risk factor for cervical cancer.
Methods
We evaluated the clinical significance of the HPV DNA chip genotyping assay (MyHPV chip, Mygene Co.) compared with the Hybrid Capture 2 (HC2) chemiluminescent nucleic acid hybridization kit (Digene Corp.) in 867 patients.
Results
The concordance rate between the MyHPV chip and HC2 was 79.4% (kappa coefficient, κ = 0.55). The sensitivity and specificity of both HPV tests were very similar (approximately 85% and 50%, respectively). The addition of HPV result (either MyHPV chip or HC2) to cytology improved the sensitivity (95%, each) but reduced the specificity (approximately 30%, each) compared with the HPV test or cytology alone. Based on the MyHPV chip results, the odds ratio (OR) for ≥ high-grade squamous intraepithelial lesions (HSILs) was 9.9 in the HPV-16/18 (+) group and 3.7 in the non-16/18 high-risk (HR)-HPV (+) group. Based on the HC2 results, the OR for ≥ HSILs was 5.9 in the HR-HPV (+) group. When considering only patients with cytological diagnoses of “negative for intraepithelial lesion or malignancy” and “atypical squamous cell or atypical glandular cell,” based on the MyHPV chip results, the ORs for ≥ HSILs were 6.8 and 11.7, respectively, in the HPV-16/18 (+) group.
Conclusions
The sensitivity and specificity of the MyHPV chip test are similar to the HC2. Detecting HPV-16/18 with an HPV DNA chip test, which is commonly used in many Asian countries, is useful in assessing the risk of high-grade cervical lesions.

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