title: Anal verrucous carcinoma is not related to infection with human papillomaviruses and should be distinguished from giant condyloma (Buschke-Löwenstein tumour).
abstract: OBJECTIVE
  Verrucous carcinoma (VC) is a variant of well-differentiated squamous cell carcinoma and in the anal region is regarded as synonymous with giant condyloma (Buschke-Löwenstein tumour) (BLT). Aetiology, diagnostic criteria and clinical behaviour of both lesions are controversial. Recent studies suggest that VC at other sites is not associated with human papillomaviruses (HPV). We hypothesized that anal VC is also not related to HPV, while BLT is a HPV-induced lesion.
  
  
  RESULTS
  Ten cases of VC and four cases of BLT were included. Several techniques were used for HPV detection: in-situ hybridization for HPV6, 11, 16 and 18, six different polymerase chain reaction (PCR) protocols for detection of at least 89 HPV types from alpha-, beta-, gamma- and mu-PV genera and in-situ hybridization for high-risk HPV E6/E7 mRNA; p16 immunohistochemistry and morphometric analysis were also performed. Alpha-, gamma- and mu-PVs were not found in any case of VC, while HPV6 was detected in all cases of BLT. p16 overexpression was not present in any of the lesions. Among microscopic features, only the absence of koilocytosis and enlarged spinous cells seem to be useful to distinguish VC from BLT.
  
  
  CONCLUSIONS
  Our results suggest that anal VC, similarly to VC at other sites, is not associated with HPV infection, and must be distinguished from BLT, which is associated with low-risk HPV. Only with well-set diagnostic criteria will it be possible to ascertain clinical behaviour and optimal treatment for both lesions.
authors.affiliation: Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Nina
authors.identifier: http://orcid.org/0000-0001-6866-3220
authors.initials: N
authors.lastname: Zidar
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Cord
authors.initials: C
authors.lastname: Langner
authors.affiliation: Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Odar
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Lea
authors.initials: L
authors.lastname: Hošnjak
authors.affiliation: University Hospital in Hradec Kralove, Hradec Králové, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Kamarádová
authors.affiliation: Sikl's Department of Pathology, Medical Faculty Hospital, Charles University, Pilsen, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Daum
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Marion J
authors.initials: MJ
authors.lastname: Pollheimer
authors.affiliation: Medical Centre IATROS, Ljubljana, Slovenia.
authors.forename: Pavle
authors.initials: P
authors.lastname: Košorok
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Mario
authors.initials: M
authors.lastname: Poljak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001005:Anus Neoplasms / Q000473:pathology / Q000821:virology*; D062688:Buschke-Lowenstein Tumor / Q000473:pathology / Q000821:virology*; D018289:Carcinoma, Verrucous / Q000473:pathology / Q000821:virology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications / Q000453:epidemiology; D016133:Polymerase Chain Reaction
keywords: Buschke-Löwenstein tumour; anal giant condyloma; anal verrucous carcinoma; human papillomaviruses