Laser capture microdissection-identified HPV genotypes associated with intra-anal high and low-grade intraepithelial lesions

Abstract

Background: Intra-anal lesions caused by human papillomavirus (HPV) can be classified as low-grade squamous intraepithelial lesions (LSIL) or high-grade squamous intraepithelial lesion (HSIL). The latter can be further subclassified histomorphologically as anal intraepithelial neoplasia (AIN)2 or AIN3. It is not known whether morphological differences within and between these categories are associated with different high-risk HPV (HR-HPV) genotypes. Methods: In a natural history study of anal HPV-related lesions in gay and bisexual men, we identified the presumed causal genotype of all HSIL present at baseline, utilizing laser capture microdissection. For comparison, we also analyzed randomly selected flat LSIL (fLSIL) and negative biopsies. Results: 244 distinct lesions from 175 men were analyzed: 149 AIN3, 64 AIN2 and 31 flat LSIL (fLSIL). HR-HPV genotypes were found in 139 (93.3%) AIN3, 55 (85.9%) AIN2 and 8 (25.8%) fLSIL. HPV16 was found in 59 (39.6%) AIN3, 11 (17.2%) AIN2 and 1 (3.2%) fLSIL. HR-HPV types were not significantly more common in AIN3 than AIN2 (p=0.08) but HPV16 was (p=0.001). HR-HPV genotypes were significantly more common in HSIL than in LSIL (p<0.001) as was HPV16 (p<0.001). None of 24 negative biopsies contained HR-HPV. Conclusions: There were differences observed between the two subdivisions of HSIL, namely AIN3 and AIN2, in proportions of causal HPV16 but not in proportions of HR-HPV overall. As HPV16 is the most carcinogenic HPV subtype, histomorphologic differences within the category of HSIL could have prognostic significance.