Human Papilloma Virus–Associated Squamous Neoplasia of the Lower Anogenital Tract

HPV-associated squamous neoplasias of the lower anogenital tract are biologically and morphologically equivalent; a unified, two-tiered nomenclature system is recommended to reflect this. Low-grade squamous intraepithelial lesion represents the morphologic manifestation of transient HPV infection with high rate of regression. High-grade squamous intraepithelial lesion (HSIL) represents the morphologic manifestation of persistent high-risk HPV infection and viral integration with a significant rate of progression to invasive carcinoma. Despite these shared attributes, SILs encounter unique diagnostic challenges by anatomic site. This article discusses the LAST project recommendations, challenges associated with their application, and site specific diagnostic challenges in their relevant clinical context.