Human papilloma virus testing in head and neck squamous cell carcinoma: how far can we go with cytology specimens?

Human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma is the most common HPV-associated head and neck carcinoma. It is biologically unique and has a better prognosis than HPV-independent squamous cell carcinoma. The most common histomorphology of HPV-associated oropharyngeal squamous cell carcinoma is nonkeratinizing basaloid form of squamous cell carcinoma. Head and neck squamous cell carcinomas clinically often present as a neck mass and cytological sample obtained by fine needle aspiration is a crucial part of diagnostic work-up and it can be the only diagnostic material available. Several cytological samples including direct smears, cytospins, cell blocks and liquid-based material can be used for p16 immunohistochemistry, high-risk (hr) HPV DNA in situ hybridization (ISH), E6/E7 hrHPV RNA ISH, and hrHPV polymerase chain reaction. Quality control issues must be considered in all detection methodologies applied in cytological material. The selection of method depends on material type, turnaround time, standardization, sensitivity, and specificity. p16 immunohistochemistry should be applied and interpreted in conjunction with squamous cell morphology and caution should arise in cases with unusual morphology. p16 positivity alone is not recommended as a diagnostic indicator.