Ancillary studies in determining human papillomavirus status of squamous cell carcinoma of the oropharynx: a review

Abstract

Squamous cell carcinoma (SCC) of the oral cavity and pharynx represents the sixth most common form of malignancy worldwide. A significant proportion of these cases are related to human papillomavirus (HPV) infection. In general, HPV-associated SCC is more commonly nonkeratinizing and poorly differentiated, whereas non-HPV-associated SCC is typically keratinizing and moderately differentiated. Nevertheless, significant overlap in morphology is seen between these two forms of SCC. The purpose of this paper is to highlight the utility of ancillary studies in the establishment of HPV status of oropharyngeal SCC, including p16 immunohistochemistry, high-risk HPV in situ hybridization, polymerase chain reaction, and newer HPV detection modalities.

Figure 1

Poorly-differentiated squamous cell carcinoma lacking clear evidence of squamous differentiation (hematoxylin and eosin) (a). In the oropharynx, these are typically HPV-associated neoplasms. Immunohistochemical stain demonstrates diffuse nuclear and cytoplasmic staining for p16 (b), while in situ hybridization highlights the presence of HPV DNA.

Figure 2

Moderately differentiated squamous cell carcinoma (hematoxylin and eosin) (a) lacking evidence of HPV infection by p16 immunohistochemical stain (b) or in situ hybridization (c). Though well and moderately-differentiated lesions tend to be negative for HPV, and poorly-differentiated lesions are typically HPV positive, there is significant morphologic overlap between HPV positive and negative tumors.