title: The variable clinicopathological categories and role of human papillomavirus in cervical adenocarcinoma: A hospital based nation-wide multi-center retrospective study across China.
abstract: We investigated HPV in adenocarcinoma presenting and managed as cervical adenocarcinoma (CADC) at seven major representative regional cancer centres across China. From 1,051 CADC cases diagnosed locally in 2005-2010, 881 had available paraffin embedded tissue. Initial review excluded 154 cases as other diagnoses or inappropriate specimens. In 718 eligible cases consensus panel pathology diagnosis was made using an algorithm incorporating p16 and progesterone receptor immunohistochemistry (IHC). Classification of cervical adenocarcinoma categories was subject to substantial pathological disagreement. High-risk human papillomaviruses (HR-HPV) DNA was studied by the sensitive SPF10 PCR-DEIA-LiPA25 version 1 for L1 genes and type-specific HR-HPV E6/7 gene PCR's. HR-HPV prevalence in whole tissue samples in eligible tested CADC was 74.5%: 100.0% in neuro-endocrine carcinoma (NEC), 82.2% in classical cervical adenocarcinoma (ADC-CX), 40.0% in adenocarcinoma-not otherwise specified (ADC-NOS) and 33.3% in endometrioid adenocarcinoma (ADC-ENDO). Higher mean age at diagnosis correlated with histological categories showing low HPV prevalence (Linear regression: β= -13.794, p < 0.001). HPV-16 and 18 were associated with early development of CADC and a lower mean age correlated with carcinogenic risk of associated HPV (β = -0.1829, p < 0.001). HPV-16 or HPV-18 was found in 88.2% of all HPV positive cases including multiple-infections. HPV-18 was the commonest HPV type in NEC (58.3%), ASC (40.2%) and ADC-CX (40.9%). The proportion of HPV-unrelated CADC and in different final histological categories varied geographically and by age. Although HPV negativity was predominantly associated with special categories of CADC, some HPV-negative usual adenocarcinomas indistinguishable by adjudicated microscopic diagnosis from ADC-CX were found and varied in frequency across China.
authors.affiliation: Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.affiliation: DDL Diagnostic Laboratory, Visseringlaan 25, 2288 ER, Rijswijk, The Netherlands.
authors.forename: Anco
authors.initials: A
authors.lastname: Molijn
authors.affiliation: Minzu University of China, Haidian District, Beijing, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Enqi
authors.affiliation: Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: DDL Diagnostic Laboratory, Visseringlaan 25, 2288 ER, Rijswijk, The Netherlands.
authors.forename: David
authors.initials: D
authors.lastname: Jenkins
authors.affiliation: Jiangxi Women and Children's Hospital, Jiangxi.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yu
authors.affiliation: DDL Diagnostic Laboratory, Visseringlaan 25, 2288 ER, Rijswijk, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Quint
authors.affiliation: GlaxoSmithKline Vaccines, Avenue Fleming 20, Wavre, Belgium.
authors.forename: Johannes E
authors.initials: JE
authors.lastname: Schmidt
authors.affiliation: Department of Occupational and Environmental Health, West China School of Public Health, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Weill Medical College of Cornell University, 525 E 68th Street, New York.
authors.forename: Edyta
authors.initials: E
authors.lastname: Pirog
authors.affiliation: Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. qiaoy@cicams.ac.cn.
authors.forename: Youlin
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: Chinese HPV typing group.
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D002681:China / Q000453:epidemiology; D004279:DNA, Viral; D005260:Female; D005838:Genotype; D006761:Hospitals; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications* / Q000453:epidemiology / Q000821:virology; D011159:Population Surveillance; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004279:DNA, Viral
keywords: cervical adenocarcinoma; human papillomavirus; immunohistochemical staining