Flat penile lesions: the infectious "invisible" link in the transmission of human papillomavirus.

Although it has been widely accepted that high-risk human papillomavirus (hrHPV) is sexually transmitted, limited insight is available about the clinical manifestations of hrHPV infection in men and their contribution in the viral spread. Here, we reviewed the literature on the relationship between hrHPV and the presence of penile lesions. Flat penile lesions have similar predilection sites as HPV, often contain hrHPV as identified by DNA in situ hybridization in biopsy specimens, show a high association with hrHPV as identified by PCR in penile scrapes of lesional sites and are associated with high viral copy numbers. Absence of flat lesions is generally associated with very low HPV copy numbers or absence of HPV. Therefore, we argue that these lesions form the reservoir of hrHPV in men and contribute to the viral spread. Their bare visibility with the naked eye and their high degree of spontaneous healing explain why flat penile lesions have slipped the attention of the clinician. Combining an HPV DNA test with a visual inspection after acetic acid application offers a more reliable interpretation of a positive HPV test in men, as it helps to distinguish positivity that is very likely to reflect a productive HPV infection from potentially HPV infections with very low copy numbers or HPV contamination by the sex partner. Future trials of HPV vaccines in men should take into account not only the presence of penile HPV but also the presence of flat penile lesions as an outcome measure for the efficacy of a vaccine.