title: Oncogenic human papillomavirus-infected immature metaplastic cells and cervical neoplasia.
abstract: Persistent cervical high-risk human papillomavirus (HR-HPV) infection results in high-grade cervical intraepithelial neoplasia (CIN2/3) and cervical carcinoma. The susceptibility of the cervix to HPV carcinogenesis and the importance of HPV18 in cervical carcinoma despite relative infrequency in CIN2/3 could be linked to HR-HPV infection of immature metaplasia (IM) at the squamocolumnar junction. Atypical IM (AIM) is an equivocal category used to describe changes in IM suggestive of high-grade neoplasia, which causes diagnostic and management problems. We used laser capture microscopy combined with polymerase chain reaction in 24 women with HPV18, HPV16, or other HPV infections on cytologic analysis and a cervical loop electrosurgical excision procedure to locate HR-HPV in cervical tissue. HPV18-positive AIM and CIN2/3 were present in 7/12 cases with HPV18 on cytologic analysis. In 2 cases with HPV18 and other HPV types, HPV18 was only present in AIM and not in CIN2/3. HPV16-positive AIM was present in 3/7 and HPV16-positive CIN2/3 in 5/7 cases with HPV16. No cases had HPV16 AIM without CIN2/3. Other HR-HPV-positive AIM and CIN2/3 cases were present, respectively, in 1/6 and 5/6 cases positive for HR-HPV types other than HPV16/18. In a subset, 94% HPV18 AIM regions showed CK17 and p16 positivity, and 41% were CK7 positive. CIN2/3 and AIM with other HR-HPVs showed similar patterns. AIM was a particular feature of HPV18 infection in women with CIN2/3. HR-HPV infection of CK7/17-positive AIM expressing p16 was particularly seen for HPV18 with and without classical CIN2/3 and should be regarded as a high-grade precancer.
authors: *DDL Diagnostic Laboratory, Rijswijk ‡Roosevelt Kliniek §Leids Cytologisch Pathologisch Laboratorium, Leiden ∥Department of Pathology, Reinier de Graaf Groep, Delft, The Netherlands †Institut Clinic of Gynecology, Obstetrics and Neonatology, IDIBAPS (Institut d´Investigacions Biomèdiques August Pi i Sunyer)-Hospital Clínic ¶Department of Pathology, CRESIB (Centre de Recerca en Salut Internacional de Barcelona)-Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors: Jacolien
authors: J
authors: van der Marel
authors: Romy
authors: R
authors: van Baars
authors: Inmaculada
authors: I
authors: Alonso
authors: Marta
authors: M
authors: del Pino
authors: Miekel
authors: M
authors: van de Sandt
authors: Jan
authors: J
authors: Lindeman
authors: Bram
authors: B
authors: ter Harmsel
authors: Mathilde
authors: M
authors: Boon
authors: Frank
authors: F
authors: Smedts
authors: Jaume
authors: J
authors: Ordi
authors: Aureli
authors: A
authors: Torné
authors: David
authors: D
authors: Jenkins
authors: Wim
authors: W
authors: Quint
mesh_terms: D002584:Cervix Uteri / Q000473:pathology / Q000821:virology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D061346:Laser Capture Microdissection; D008679:Metaplasia / Q000821:virology*; D065006:Papanicolaou Test; D030361:Papillomavirus Infections / Q000150:complications / Q000821:virology*; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000821:virology*; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000821:virology*