P16INK4/Ki-67 Dual-Staining Expression as a Prognostic Indicator in Laryngeal Cancer

Abstract

Human Papilloma Virus (HPV) infection is thought to play a role in laryngeal carcinogenesis; particularly, p16 expression has been reported as a surrogate marker for high-risk HPV (HR-HPV) infection, associated with a subgroup of laryngeal cancers showing favourable prognosis. To evaluate HPV status, different detection molecular tests have been used and a large variation of HPV prevalence has been reported. The aim of the study was to detect HPV status by an immunohistochemical retrospective study conducted on seventy-three T1 N0 or carcinoma in situ (CIS) laryngeal biopsies, using a new established dual-staining test (p16/Ki-67), which might improve the specificity of the assay. Overall, 18 of 73 cases (25%) were p16-positive: Verrucoid carcinomas showed p16 expression in almost all samples (87.5%), whereas all G3 tumours were p16-negative. Patients with p16-negative tumours were more likely to relapse (83%) than p16-positive cancers (17%). Moreover, HPV genotyping detection was conducted on all 73 cases: 25% were classified as HPV+ and 75% were classified as HPV-; HPV+/p16+ cases were associated to HR-HPV whereas HPV+/p16- samples (2 cases) were associated to LR-HPV. In consideration of these findings, investigation of p16 expression by the dual-staining test is sought as technically simple and potentially reliable assay for HR-HPV induced laryngeal cancers thus to be predictive of clinical outcome.