Detection of human papillomavirus in branchial cleft cysts.

High-risk human papillomavirus (HPV) DNA has been reported to be present in branchial cleft cysts, but further information is required to clarify the role of HPV infection in branchial cleft cysts. The presence of HPV, the viral load and the physical statuses in samples from six patients with branchial cleft cysts were investigated using the polymerase chain reaction (PCR), quantitative PCR, in situ hybridization (ISH) using HPV DNA probes and p16(INK4a) immunohistochemical analysis. High-risk type HPV-16 DNA was identified in four of the six branchial cleft cysts analyzed. Of the HPV-positive branchial cleft cysts, three exhibited mixed-type integration of HPV. HPV DNA was distributed among the basal-to-granular layers of the cystic wall in ISH analysis, and p16(INK4a) was weakly expressed in the nuclei and cytoplasm of the same layers in patients with integration. ISH revealed that one patient with episomal-type infection exhibited HPV DNA in the cyst wall and did not express p16(INK4a). Two patients without evidence of HPV infection exhibited weak p16(INK4a) expression in the superficial cyst-lining cells of branchial cleft cysts. These results indicate that infection with high-risk HPV types may be common in branchial cleft cysts. In addition, p16(INK4a) is not a reliable surrogate marker for HPV infection in branchial cleft cysts.