Squamous intraepithelial lesions of the anal squamocolumnar junction: Histopathological classification and HPV genotyping

Abstract

BackgroundHuman papillomavirus (HPV)-related anal cancer lesions are often found adjacent to the squamocolumnar junction (SCJ). We have assessed the histopathology and associated HPV genotypes in anal SCJ lesions in surgically excised anal warts in HIV-negative and –positive patients.MethodsHistopathology identified 47 squamous intraepithelial lesions (SILs) adjacent to the SCJ amongst a total of 145 cases of clinically diagnosed anal condylomata. The anal SCJ lesions were further analyzed with p16, CK7 and p63 immunohistochemistry and HPV genotyping.ResultsSixteen (16/47) of the excised anal wart lesions contained HSIL; Three were HSIL and exclusively associated with oncogenic HPVs. A further thirteen (13/47) were mixed lesions. Of these eight were HSILs with LSIL and six were HSILs with papillary immature metaplasia (PIM); Ten of the mixed lesions were associated with one or more oncogenic HPVs, while three cases were exclusively associated with HPV6.ConclusionsClinically diagnosed anal warts cannot be assumed to be limited to low-grade lesions as anal warts of the SCJ often show heterogeneous lesions, with coexistence of LSIL, PIM, and HSIL. Lesions showing PIM, however, may mimic HSIL, because they are hypercellular, but lack the nuclear atypia and conspicuous mitotic activity of HSIL; and are p16 negative.

A Novel Model for Papillomavirus-Mediated Anal Disease and Cancer Using the Mouse Papillomavirus

“…6 ), which has previously been shown to be susceptible to MmuPV1 infection ( 28 , 40 ). We robustly demonstrate this localization effect by comparing viral infection biomarkers to p63 and K7 biomarkers characterizing the anal microanatomical zones ( 44 , 45 ). Notably, we find that areas of persistent MmuPV1 infection often correspond to areas with high levels of K7 expression in the suprabasal layers marking the transition zone, and that this effect is independent of infection methodology.…”

“…Disease was localized to the anal transition zone in seven of the eight (87.5%) mice with HSIL. The anal transition zone, also referred to as the squamocolumnar junction or the anorectal junction, is the microanatomical area where the epithelium transitions from the columnar epithelium of the rectum to the stratified squamous epithelium that comprises the most caudal region of the anal canal and the perianal skin ( 44 , 45 ) and had been previously shown by Cladel and colleagues to be susceptible to MmuPV1 infection ( 40 ).…”

“…Based on our initial observation that MmuPV1-mediated disease in NSG mice localized to the anal transition zone, we hypothesized that the transition zone and the stratified squamous epithelium immediately adjacent to it is a preferential site for the establishment of MmuPV1 infection and disease in the anal tract. The anal transition zone is characterized by a distinct pattern of expression of keratin 7 (K7) and p63 ( 44 , 45 ). Using these biomarkers, the microanatomy of the anal canal can be broken down into three distinct regions: the caudal, stratified squamous epithelium characterized by p63-positive nuclei in the basal layer and K7-negative suprabasal layers, the anal transition zone characterized by K7 expression in the suprabasal layers and p63-positive nuclei in the basal layer, and the columnar epithelium characterized by p63-negative nuclei ( Fig.…”

p16 immunostaining in histological grading of anal squamous intraepithelial lesions: a systematic review and meta-analysis

“…All studies included were observational. Most of them were conducted in USA (10 studies) [6,7,[15][16][17][18][19][20][21][22], two were performed in Germany [23,24], and one study each in Spain [25], Portugal [26], and Ireland [27]. Six did not describe the population from which ASIL samples were obtained [7,[16][17][18][19]22].…”

mRNA Detection in Anal Cytology: A Feasible Approach for Anal Cancer Screening in Men Who Have Sex with Men Living With HIV

“…p16 immunohistochemical staining was performed in all the cervical samples obtained. A positive block staining for p16 in the dysplastic area was required for the diagnosis of HSIL/AIN2-3 [23].…”