title: Human Papillomavirus Genotyping of Incidental Malignant and Premalignant Lesions on Hemorrhoidectomy Specimens.
abstract: Routine histopathologic examination of hemorrhoidectomy specimens is controversial having been described as not useful and expensive with few of these common cases demonstrating incidental lesions. However, unexpected premalignant and malignant lesions have been detected on excised hemorrhoids. The high-risk human papillomavirus (HR-HPV) types associated with these incidentally identified high-grade lesions are presently unknown. We aimed to identify cases of incidental high-grade anal intraepithelial neoplasia (HG-AIN) and anal squamous cell carcinoma incidentally discovered on hemorrhoidectomy specimens, genotype HR-HPVs from these lesions, and assess p53 and p16 expression by immunohistochemistry to identify risk factors for their development. With institutional approval, cases with associated demographics from 1995 to 2015 were reviewed to identify and confirm incidental HG-AIN or squamous cell carcinoma in hemorrhoidectomy specimens. Genotyping for HR-HPV types and immunohistochemical staining for p53 and p16 was performed. Statistical analysis comparing HPV genotypes, p53 and p16 staining, and potential risk factors by the Fisher exact test was performed. In the largest series of incidental high-grade lesions on hemorrhoidectomy, HPV 16 was the most common HR-HPV detected though multiple-type infections were common including some HPV 16/18-negative cases. By genotyping, HPV 39 was significantly associated with IV-drug abuse history (P=0.0015) and HIV-positive status (P=0.037), whereas HPV 58 detection correlated with chemotherapy-induced immunosuppression (P=0.029). There was frequent overlap between p53 staining and HPV positivity, particularly when HPV 31 was detected. We also identified several mimickers of HG-AIN that may present diagnostic challenges in these specimens. Our data support continued routine examination of hemorrhoidectomy specimens and suggest that adjunctive studies such as immunohistochemistry for challenging cases may be useful.
authors.affiliation: Departments of *Pathology and Laboratory Medicine, Rhode Island Hospital †Pathology and Laboratory Medicine, Women and Infants Hospital of Rhode Island ‡Pathology and Laboratory Medicine §Pathology and Laboratory Medicine, The Miriam Hospital, Alpert Medical School of Brown University, Providence, RI.
authors.forename: Yiang
authors.initials: Y
authors.lastname: Hui
authors.forename: M Ruhul
authors.initials: MR
authors.lastname: Quddus
authors.forename: Jayasimha N
authors.initials: JN
authors.lastname: Murthy
authors.forename: Dongfang
authors.initials: D
authors.lastname: Yang
authors.forename: C James
authors.initials: CJ
authors.lastname: Sung
authors.forename: Shaolei
authors.initials: S
authors.lastname: Lu
authors.forename: Murray B
authors.initials: MB
authors.lastname: Resnick
authors.forename: Li Juan
authors.initials: LJ
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D001005:Anus Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000821:virology*; D002278:Carcinoma in Situ / Q000175:diagnosis / Q000473:pathology / Q000821:virology*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000473:pathology / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques; D061865:Hemorrhoidectomy; D006801:Humans; D033162:Incidental Findings; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics* / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis* / Q000821:virology; D011230:Precancerous Conditions / Q000175:diagnosis / Q000473:pathology / Q000821:virology*; D012189:Retrospective Studies
chemical_list: D004279:DNA, Viral