Human Papillomavirus Genotypes in Anal High-Grade Squamous Intraepithelial Lesion (HSIL): Anal Intraepithelial Neoplasia Grades 2 (AIN2) and 3 (AIN3) Are Different

Abstract

Background: Anal high-grade squamous intraepithelial lesion (HSIL) can be histomorphologically categorized into anal intraepithelial neoplasia (AIN) grade 2 (AIN2) and grade 3 (AIN3). Different risk factors for these two categories have been described. We investigated whether there were also differences in lesion-specific human papillomavirus (HPV) genotypes.

Methods: The Study of the Prevention of Anal Cancer (SPANC) recruited 617 gay and bisexual men (GBM); 36% of participants were HIV positive. At baseline, 196 men (31.8%) had histologic HSIL lesions. Tissue was available for genotyping in 171, with a total of 239 HSIL lesions (183 AIN3 and 56 AIN2). Using laser capture microdissection, each lesion revealed a maximum of one genotype.

Results: High-risk HPV (HR-HPV) genotypes were found in 220 (92.1%) HSIL lesions, with no significant difference between AIN3 (93.4%) and AIN2 (87.5%). AIN3 lesions had significantly more HPV16 (42.1%) than AIN2 lesions (12.5%; P < 0.001) and AIN2 lesions had significantly more non-16 HR-HPV types (75.0%) than AIN3 lesions (51.4%; P = 0.002). These associations were similar for HIV-negative men with HPV16 in 51.1% AIN3 and 18.2% AIN2 (P = 0.001) and non-16 HR-HPV in 40.0% AIN3 and 75.8% AIN2 (P < 0.001). For HIV-positive men, HPV16 remained more frequently detected in AIN3 (33.3% vs. 4.4% for AIN2; P = 0.004), but there was no difference between AIN3 and AIN2 for non-16 HR-HPV (62.4% vs. 73.9%; P = 0.300).

Conclusions: As HPV16 has the strongest link with anal cancer, the subcategorization of HSIL may enable stratification of lesions for anal cancer risk and guide anal HSIL management.

Impact: Stratification of anal cancer risk by histologic HSIL grade.