{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T03:02:05Z","timestamp":1773889325186,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,9,3]],"date-time":"2015-09-03T00:00:00Z","timestamp":1441238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology","award":["2013R1A1A2009971"],"award-info":[{"award-number":["2013R1A1A2009971"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Although patients found to have atypical squamous cells of undetermined significance (ASC\u2010US) and low\u2010grade squamous intraepithelial lesions (LSILs) on Papanicolaou (Pap) testing are treated conservatively, 5.2% to 18.8% of them progress to high\u2010grade squamous intraepithelial lesions (HSILs). The objective of the current study was to identify predictors of progression to HSIL and determine what percentage of ASC\u2010US\/LSIL cases harbor cervical intraepithelial neoplasia of grade 2 or higher.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>The current study included 381 consecutive cases with ASC\u2010US\/LSIL. After the exclusion of 87 cases because of a history of dysplasia or loss to follow\u2010up, 165 cases with follow\u2010up cytology were used to analyze predictive factors of progression to HSIL, and 129 cases that underwent immediate tissue biopsy were subjected to correlation analysis between cytology and histology. Disease regression was defined as a reversion to normal or benign cellular changes, disease persistence as maintenance at ASC\u2010US\/LSIL, and disease progression as progression to HSIL. Data regarding clinical parameters were obtained from medical records. Methylation\u2010specific polymerase chain reaction was performed using cytology samples to evaluate methylation of the p16 promoter.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Of 165 cases, 131 (79.4%) regressed, 23 (13.9%) were persistent, and 11 cases (6.7%) progressed. Human papillomavirus infection was more common in women with disease progression than in those with disease regression or persistence (<jats:italic>P\u2009=<\/jats:italic>\u2009.033). Promoter methylation of p16 in the cytology sample was more common in cases that progressed (5 of 6 cases) than in cases that regressed (0 of 8 cases). Twenty\u2010three of 129 cases (17.8%) were found to harbor cervical intraepithelial neoplasia of grade 2 or higher on immediate tissue biopsy.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Human papillomavirus infection and p16 promoter methylation might be valuable surrogate markers of disease progression from ASC\u2010US\/LSIL to HSIL. <jats:bold><jats:italic>Cancer (Cancer Cytopathol)<\/jats:italic> 2016;124:58\u201365.<\/jats:bold> \u00a9 <jats:italic>2015 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.21615","type":"journal-article","created":{"date-parts":[[2015,9,3]],"date-time":"2015-09-03T11:40:47Z","timestamp":1441280447000},"page":"58-65","source":"Crossref","is-referenced-by-count":13,"title":["HPV infection and p16 promoter methylation as predictors of ASC\u2010US\/LSIL progression"],"prefix":"10.1002","volume":"124","author":[{"given":"Hee","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Chung\u2010Ang University Hospital Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun\u2010Ju","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Chung\u2010Ang University Hospital Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,9,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.5858\/2003-127-946-FTDFTA"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19980225)84:1<5::AID-CNCR2>3.0.CO;2-Q"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/LGT.0b013e3182730fec"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(03)00418-6"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(03)00413-7"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1994.03510470070037"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.171"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2012.06.095"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.21240"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066587"},{"key":"e_1_2_7_12_1","first-page":"4525","article-title":"Inactivation of the CDKN2\/p16\/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers","volume":"55","author":"Herman JG","year":"1995","journal-title":"Cancer Res."},{"key":"e_1_2_7_13_1","first-page":"584","article-title":"Aberrant methylation during cervical carcinogenesis","volume":"7","author":"Virmani AK","year":"2001","journal-title":"Clin Cancer Res."},{"key":"e_1_2_7_14_1","first-page":"1982","article-title":"Promoter hypermethylation of multiple genes in carcinoma of the uterine cervix","volume":"7","author":"Dong SM","year":"2001","journal-title":"Clin Cancer Res."},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2003.09.036"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2011.113"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/PDM.0b013e3181aa8f64"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/IGC.0b013e31821091ea"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2005.20.4.636"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/030089160709300610"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.16.2114"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.656.11.2"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e3182883a34"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2015.01.007"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.1174"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65689-1"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2014.07.007"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3181709fbf"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.22.12754"},{"key":"e_1_2_7_30_1","first-page":"229","article-title":"Common problems in Papanicolaou smear interpretation","volume":"121","author":"DeMay RM","year":"1997","journal-title":"Arch Pathol Lab Med."},{"key":"e_1_2_7_31_1","first-page":"263","article-title":"Cervical cytologic reports of ASCUS and LSIL. 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