title: Absence of high-risk human papillomavirus (HPV) detection in endocervical adenocarcinoma with gastric morphology and phenotype.
abstract: A subset of endocervical-type mucinous adenocarcinomas (ACs) of the uterine cervix exhibit a gastric phenotype and morphology, as reported in cases of minimal deviation AC in which the presence of human papillomavirus (HPV) has been rarely detected. To investigate the HPV-independent pathway of carcinogenesis in cases of gastric-type AC, we investigated the common high-risk HPV (hr-HPV) status in 52 nonsquamous cell carcinomas, using a PCR-based typing method and immunohistochemistry of p16INK4a (a cyclin-dependent kinase inhibitor that is overexpressed in both cancerous and precancerous cervical tissue, making it an ideal biomarker for cervical cancer cases). Using novel morphological criteria, seven of 52 (13.5%) carcinomas were designated as gastric-type ACs, all of which were negative for both hr-HPV DNA and p16INK4a. Nongastric-type ACs were frequently positive for both hr-HPV DNA (90%, 28/31) and p16INK4a (94%, 29/31) with adenosquamous and neuroendocrine carcinomas demonstrating the presence of hr-HPV DNA in 86% (6/7) and 83% (5/6) of cases, respectively. In these two types of carcinoma, 86% (6/7) and 100% (6/6) were positive for p16INK4a, respectively. Our data suggests that gastric-type AC appears to represent an oncogenic hr-HPV-independent neoplasm and therefore is a potential pitfall of HPV DNA testing and vaccination.
authors.affiliation: Department of Obstetrics and Gynecology, Ehime University Graduate School of Medical Science, Toon, Ehime, Japan.
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Kusanagi
authors.forename: Atsumi
authors.initials: A
authors.lastname: Kojima
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Mikami
authors.forename: Takako
authors.initials: T
authors.lastname: Kiyokawa
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sudo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Nishimura
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000821:virology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007564:Japan / Q000453:epidemiology; D027383:Papillomaviridae / Q000235:genetics / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000473:pathology*; D039781:PubMed; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000821:virology*
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral