{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T15:15:23Z","timestamp":1771168523989,"version":"3.50.1"},"reference-count":65,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:00:00Z","timestamp":1692835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Government Budget","award":["GB-A_60_010_30_05"],"award-info":[{"award-number":["GB-A_60_010_30_05"]}]},{"name":"Government Budget","award":["HEA663000055"],"award-info":[{"award-number":["HEA663000055"]}]},{"name":"Thailand Science Research and Innovative Fund Chulalongkorn University","award":["GB-A_60_010_30_05"],"award-info":[{"award-number":["GB-A_60_010_30_05"]}]},{"name":"Thailand Science Research and Innovative Fund Chulalongkorn University","award":["HEA663000055"],"award-info":[{"award-number":["HEA663000055"]}]},{"name":"Chulalongkorn University","award":["GB-A_60_010_30_05"],"award-info":[{"award-number":["GB-A_60_010_30_05"]}]},{"name":"Chulalongkorn University","award":["HEA663000055"],"award-info":[{"award-number":["HEA663000055"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Cervical cancer screening typically involves a Pap smear combined with high-risk human papillomavirus (hr-HPV) detection. Women with hr-HPV positivity but normal cytology, as well as those with precancerous abnormal cytology, such as low-grade squamous intraepithelial lesions (LSIL) and high-grade SIL (HSIL), are referred for colposcopy and histology examination to identify abnormal lesions, such as cervical intraepithelial neoplasia (CIN) and cervical cancer. However, in order to enhance the accuracy of detection, bioinformatics analysis of a microarray database was performed, which identified cg01009664, a methylation marker of the thyrotropin-releasing hormone (TRH). Consequently, a real-time PCR assay was developed to distinguish CIN2+ (CIN2, CIN3, and cervical cancer) from CIN2- (CIN1 and normal cervical epithelia). The real-time PCR assay utilized specific primers targeting methylated cg01009664 sites, whereas an unmethylated reaction was used to check the DNA quality. A cut-off value for the methylated reaction of Ct &lt; 33 was established, resulting in improved precision in identifying CIN2+. In the first cohort group, the assay demonstrated a sensitivity of 93.7% and a specificity of 98.6%. In the cytology samples identified as atypical squamous cells of undetermined significance (ASC-US) and LSIL, the sensitivity and specificity for detecting CIN2+ were 95.0% and 98.9%, respectively. However, when self-collected samples from women with confirmed histology were tested, the sensitivity for CIN2+ detection dropped to 49.15%, while maintaining a specificity of 100%. Notably, the use of clinician-collected samples increased the sensitivity of TRH methylation testing. TRH methylation analysis can effectively identify women who require referral for colposcopy examinations, aiding in the detection of CIN2+.<\/jats:p>","DOI":"10.3390\/v15091802","type":"journal-article","created":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T10:09:53Z","timestamp":1692871793000},"page":"1802","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Efficiency of CIN2+ Detection by Thyrotropin-Releasing Hormone (TRH) Site-Specific Methylation"],"prefix":"10.3390","volume":"15","author":[{"given":"Arkom","family":"Chaiwongkot","sequence":"first","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Center of Excellence in Applied Medical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Supranee","family":"Buranapraditkun","sequence":"additional","affiliation":[{"name":"King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand"},{"name":"Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Center of Excellence in Vaccine Research and Development (Chula Vaccine Research Center-(Chula VRC)), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3738-7061","authenticated-orcid":false,"given":"Shina","family":"Oranratanaphan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thanaporn","family":"Chuen-Im","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Science, Silpakorn University, Nakhon Pathom 73000, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nakarin","family":"Kitkumthorn","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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