Histopathologic Examination of Penile Epithelial Lesions Is of Limited Diagnostic Value in Human Papillomavirus Infection

Background and Objectives: Guidelines for the histopathologic diagnosis of human papillomavirus (HPV) infection have been drawn from changes seen in cervical specimens not necessarily applicable to penile epithelium. Goal: To evaluate histopathologic examination as a means of diagnosing HPV infection of the male genital tract. Study Design: Ninety‐two consecutive male patients seen at the sexually transmitted diseases clinic. Twelve had condyloma acuminatum, and 80 had papular lesions, macular lesions, or both. Fifteen men without signs of HPV infection served as controls. Biopsy specimens were evaluated morphologically by light microscopy, and HPV DNA detection was performed by in situ hybridization and polymerase chain reaction. Results: All acuminate lesions were HPV DNA positive with in situ hybridization. Forty papular and/or macular lesions harbored HPV DNA, 28 (35%) of them positive with in situ hybridization and the other 12 (15%) positive with polymerase chain reaction. Morphologic signs attributed to HPV infection were found in HPV‐positive and HPV‐negative penile lesions, as well as in normal epithelium. In papular and macular lesions, the only criterion associated with HPV DNA positivity was neoplastic changes, which was present in 16 (40%) HPV DNA‐positive specimens, compared to 4 (10%) HPV DNA‐negative specimens (P < 0.01). Of the 16 lesions with neoplasia, 15 (94%) had detectable HPV DNA of a potentially oncogenic type. Conclusions: Histopathologic signs of HPV infection other than neoplasia seem to be of limited value. Detection of the infectious agent, in this case HPV, should be the gold standard for the diagnosis as it is for other infectious diseases. The strong association between neoplasia and potentially oncogenic HPV types makes this issue even more important.