p16INK4/Ki-67 Dual-Staining Expression as a Prognostic Indicator in Laryngeal Cancer

Abstract

Among head and neck Squamous cell carcinomas (HNSCCs), the larynx is one of the sites most involved, being traditionally associated with tobacco and alcohol use, especially when in combination [1]. As squamous carcinoma develops throughout a step progression in various stages of dysplasia, many molecular changes have been described [2]. The implication of Human Papilloma Virus (HPV) in HNSCC development [3,4], particularly, the infection with high-risk HPV types (HR-HPV) has also been etiologically linked with a subset of laryngeal carcinoma [5] thus suggesting a different carcinogenetic pathway. Studies regarding HPV induced laryngeal cancers indicate that they are associated with improved outcomes [6], moreover they have more favorable prognosis when treated with surgery alone [7]. At present, the causal role of HR-HPV in laryngeal carcinogenesis is controversial, mainly because no unanimously accepted detection method exists. Commonly used HPV detection methods for formalin fixed paraffin embedded tissue include: HPV consensus PCR method, type specific HPV detection by fluorescence in situ hybridization (FISH) and real-time PCR assays. Alternatively, the role of p16INK4a protein has been reported to identify HPVrelated laryngeal cancers [8]: hypermethylation and underp16INK4/Ki-67 Dual-Staining Expression as a