title: A Composite Cytology-Histology Endpoint Allows a More Accurate Estimate of Anal High-Grade Squamous Intraepithelial Lesion Prevalence.
abstract: There is debate about the accuracy of anal cytology and high-resolution anoscopy (HRA), in the diagnosis of anal human papillomavirus (HPV)-related squamous intraepithelial lesions (SIL). Few studies have performed both simultaneously in a large sample of high-risk individuals.
  
  
  
  At baseline in a community-based cohort of HIV-infected and uninfected homosexual men ages ≥35 years in Sydney, Australia, all men underwent anal swabbing for cytology and HPV genotyping, and HRA-guided biopsy. We evaluated the separate and combined diagnostic accuracy of cytology and histology, based on a comparison with the prevalence of HPV16 and other high-risk (HR) HPV. We examined trends in HPV prevalence across cytology-histology combinations.
  
  
  
  Anal swab, HRA, and HPV genotyping results were available for 605 of 617 participants. The prevalence of cytologically predicted high-grade SIL (HSIL, 17.9%) was lower than histologically diagnosed HSIL (31.7%, P < 0.001). The prevalence of composite-HSIL (detected by either method) was 37.7%. HPV16 prevalence was similar in men with HSIL by cytology (59.3%), HSIL by histology (51.0%), and composite-HSIL (50.0%). HPV16 prevalence was 31.1% in men with composite-atypical squamous cells suggestive of HSIL, to 18.5% in men with composite-low-grade SIL, to 12.1% in men with composite-negative results (Ptrend < 0.001).
  
  
  
  Significantly more HSIL was detected when a composite cytology-histology endpoint was used. Increasing grade of composite endpoint was associated with increasing HPV16 prevalence.
  
  
  
  These data suggest that a composite cytology-histology endpoint reflects meaningful disease categories and is likely to be an important biomarker in anal cancer prevention. Cancer Epidemiol Biomarkers Prev; 25(7); 1134-43. ©2016 AACR.
authors.affiliation: HIV Epidemiology and Prevention Program, The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia. Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Melbourne, Australia. Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Dorothy A
authors.initials: DA
authors.lastname: Machalek
authors.affiliation: HIV Epidemiology and Prevention Program, The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia.
authors.forename: I Mary
authors.initials: IM
authors.lastname: Poynten
authors.affiliation: HIV Epidemiology and Prevention Program, The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia.
authors.forename: Fengyi
authors.initials: F
authors.lastname: Jin
authors.affiliation: Western Sydney Sexual Health Centre, University of Sydney, Sydney, Australia. St Vincent's Hospital, Sydney, Australia.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hillman
authors.affiliation: HIV Epidemiology and Prevention Program, The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia. RPA Sexual Health, Sydney Local Health District, Sydney, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Templeton
authors.affiliation: St Vincent's Hospital, Sydney, Australia.
authors.forename: Carmella
authors.initials: C
authors.lastname: Law
authors.affiliation: Douglass Hanly Moir Pathology, Sydney, Australia.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Roberts
authors.affiliation: Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Melbourne, Australia. Murdoch Childrens Research Institute, Melbourne, Australia. Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Australia.
authors.forename: Sepehr N
authors.initials: SN
authors.lastname: Tabrizi
authors.affiliation: Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Melbourne, Australia. Murdoch Childrens Research Institute, Melbourne, Australia. Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Australia.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Garland
authors.affiliation: Douglass Hanly Moir Pathology, Sydney, Australia.
authors.forename: Annabelle
authors.initials: A
authors.lastname: Farnsworth
authors.affiliation: Melbourne Sexual Health Centre, Alfred Health, Melbourne, Australia. Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Fairley
authors.affiliation: HIV Epidemiology and Prevention Program, The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia. agrulich@kirby.unsw.edu.au.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Grulich
mesh_terms: D000328:Adult; D001005:Anus Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000821:virology; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000453:epidemiology / Q000821:virology; D016022:Case-Control Studies; D015331:Cohort Studies; D023381:Endpoint Determination; D006801:Humans; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis*; D011230:Precancerous Conditions / Q000175:diagnosis; D015995:Prevalence; D011446:Prospective Studies; D012680:Sensitivity and Specificity