A composite cytology-histology endpoint allows a more accurate estimate of anal high-grade squamous intraepithelial lesion prevalence

Dorothy A. Machalek, I. Mary Poynten, Fengyi Jin, Richard J. Hillman, David J. Templeton, Carmella Law, Jennifer M. Roberts, Sepehr N. Tabrizi, Suzanne M. Garland, Annabelle Farnsworth, Christopher K. Fairley, Andrew E. Grulich*, Brian Acraman, Marjorie Adams, Andrew Carr, Susan Carroll, David Cooper, Alyssa Cornall, Leonie Crampton, Deborah EkmanKit Fairley, Lance Feeney, Eddie Fraissard, Kirsten Howard, Matthew Law, Kirsten McCaffery, Ross McDonald, Patrick McGrath, Robert Mellor, Richard Norris, Matthew O'Dwyer, Susan Pendlebury, Kathy Petoumenos, Samuel Phillips, Garrett Prestage, Adele Richards, Lance Schema, Daniel Seeds, Eva Segelov, Dave Templeton, Julia Thurloe, Winnie Tong, Rick Varma

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


Background: 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. Methods: 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. Results: 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 compositenegative results (Ptrend < 0.001). Conclusions: Significantly more HSIL was detected when a composite cytology-histology endpoint was used. Increasing grade of composite endpoint was associated with increasing HPV16 prevalence. Impact: 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.

Original languageEnglish
Pages (from-to)1134-1143
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Issue number7
Publication statusPublished - Jul 2016
Externally publishedYes


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