Leeman A, et al. - In this investigation, researchers sought to discriminate transforming and productive high-grade anal squamous intraepithelial lesions (HSIL) as a potential basis for more selective treatment by classifying immunohistochemical (IHC) biomarkers p16 and E4 in lr- and hr-HPV- associated SIL. In 183 biopsies from 108 HIV+ MSM, immunostaining for p16 and HPV E4 was performed and graded. In the HSIL group identified by the Lower Anogenital Squamous Terminology guidelines, the combined p16/E4 IHC identifies productive and non-productive HSIL associated with hrHPV. This makes it possible to investigate the selective treatment of advanced transforming HSIL caused by hrHPV and a policy of "wait and see" for productive HSIL.