A comparison of p16 INK4A immunohistochemistry, chromogenic in situ hybridization, and polymerase chain reaction genotyping for screening for human papillomavirus in basaloid squamous carcinoma.

Human papillomaviruses (HPV) can promote tumorigenesis at various anatomical sites in the body. Screening for dysplastic changes caused by HPV has decreased the morbidity and mortality due to invasive cervical cancer. Over the last two decades, HPV detection has included molecular methods as an adjunct to traditional Papanicolaou test for cervical cancer screening. HPV-positive HNSCC, specifically high risk HPV-16, have been recognized as a distinct molecular, behavioral and clinical subtype than HPV-negative tumors and therefore the importance of HPV detection in the head and neck region is becoming clear. On the molecular level, oncogenic HPV has two viral genes that synergistically cause deregulation of the cell cycle and malignant transformation. Specifically, viral proteins E6 and E7 act to degrade p53 and retinoblastoma gene family proteins (Rb), respectively. Inhibition of these tumor suppressor genes provokes a cascade of events that causes two points of interest: cell proliferation that escapes normal DNA check points and p16INK4A over-expression. Physiologically, p16INK4A is a cyclin-dependent kinase inhibitor that acts to offset the downstream actions of E6. With increase E6 activity, there is increase p16INK4A expression. Through another mechanism, with the degradation of Rb by E7, the transcription factor E2F is released and this also promotes p16INK4A synthesis. The purpose of this study was to evaluate correlation of HPV detection when using polymerase chain reaction (PCR), chromogenic in situ hybridization (CISH) or p16 immunohistochemistry (IHC), to determine p16INK4A could be used as a surrogate marker for HPV detection. Figure 1: Focal p16 IHC pattern (A) vs. diffuse p16 IHC pattern (B). Both at 40x magnification.