A Composite Cytology-Histology Endpoint Allows a More Accurate Estimate of Anal High-Grade Squamous Intraepithelial Lesion Prevalence.

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 composite-negative 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. Cancer Epidemiol Biomarkers Prev; 25(7); 1134-43. ©2016 AACR. ©2016 American Association for Cancer Research.