Human papillomavirus genotypes in anal high-grade squamous intraepithelial lesion (HSIL): anal intraepithelial neoplasia grades 2(AIN2) and 3(AIN3) are different.

Background:Anal high-grade squamous intraepithelial lesion (HSIL) can be histomorphologically categorised 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% 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=.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 subcategorisation of HSIL may enable stratification of lesions for anal cancer risk and guide anal HSIL management. Impact:Stratification of anal cancer risk by histological HSIL grade.