Human papillomavirus infection in B owen disease: Negative p53 expression, not p16 INK 4a overexpression, is correlated with human papillomavirus‐associated B owen disease

Genital B owen disease ( BD ) has been linked to the high‐risk types of human papillomavirus ( HPV ) infection. Recently, it has been recognized that HPV also can be associated with extragenital BD . HPV oncoproteins E 6 and E 7 interfere with the function of p53 and p R b, respectively, leading carcinogenesis. p16 INK 4a overexpression induced by inactivation of p R b is recognized as a surrogate marker for HPV ‐associated cervical cancer. In this study, we examined the presence of HPV DNA in 142 BD lesions by polymerase chain reaction ( PCR ), and determined the type of HPV by PCR restriction fragment length polymorphism or direct DNA sequencing. HPV DNA was detected in 66.7% of genital BD and 8.3% of extragenital BD . The types of HPV detected were HPV types 6, 16, 33, 52, 56, 58 and 59. We also investigated the expression of p16 INK 4a , p R b and p53 by immunohistochemistry. Positive expression was detected in 88.6% for p16 INK 4a , 25.2% for p R b, and 63.8% for p53. There was no significant difference in p16 INK 4a and p R b expression between HPV ‐positive and ‐negative BD . However, a strong correlation of HPV positivity with p53 negativity was found. A total of 66.7% of HPV ‐positive BD showed no p53 expression, whereas the corresponding rate was 32.8% of HPV ‐negative BD . This study demonstrated that HPV can participate in the development of BD , not only in the genital lesion, but also in extragenital lesion. p16 INK 4a overexpression is not a marker for HPV infection in BD . Instead, negative p53 expression is correlated with HPV ‐associated BD .