Relationship Between Human Papillomavirus and Penile Cancer

Implications for Prevention and Treatment

Laura C. Kidd; Sharon Chaing; Juan Chipollini; Anna R. Giuliano; Philippe E. Spiess; Pranav Sharma


Transl Androl Urol. 2017;6(5):791-802. 

In This Article

HPV and Pre-neoplastic Lesions

HPV infection can result in two types of external genital lesions depending on how the virus affects the squamous epithelium. One type is condyloma acuminata (genital warts), which are low grade lesions resulting from the production of virus in the squamous epithelium due to a transient HPV viral infection. The other type of external genital lesions are undifferentiated PeIN, which are HPV viral-associated precancerous lesions, a result of viral genome integration into the host genome leading to overexpression of oncogene, driving cell proliferation leading to malignant transformation.[34] PeIN lesions have a broad range of morphology and can be classified as differentiated and undifferentiated.[59] Differentiated PeIN is usually associated with nonviral factors (e.g., chronic inflammation, lichen sclerosis, phimosis) and is anticipated to progress to well-differentiated and keratinized SCC.[60] Undifferentiated PeIN is usually associated with HPV infection and is considered to be a precancerous lesion that progresses to basaloid and warty subtypes of SCC.[61] Alemany et al. executed a large international study from 25 countries to explore HPV prevalence in penile cancer tumors and precancerous lesions. This study diagnosed 85 precancerous lesions and 1,010 penile cancers in which HPV DNA was found in 87.1% of precancerous lesions and 33.1% of penile tumors.[62]

Aynaud et al. found HPV DNA in approximately 75% of Grade I PeIN, 93% of Grade II PeIN, and 100% of Grade III PeIN.[63] Sudenga et al. studied 1,788 HPV-positive men and found that 92 acquired external genital lesions, with 9 developing PeIN and 86 developing condyloma.[39] In both of these studies, HPV-16 was found in a vast majority of PeIN lesions. In a study of males from varying age groups, the prevalence of HPV in prepuce samples absent of external lesions were examined for high-risk HPV subtypes. High-risk HPV subtypes were found in 45.5% of children (0–10 years old), 60.6% of adolescents (11–20 years old), and 58.3% in adults (>20 years old). The highest prevalence (59.8%) was shown in age groups that had estimated higher rates of sexual activity (>14 years old).[64] These results indicate that although PeIN transformation is a rare event, high-risk HPV infection is common in males and supports vaccination protocols in boys and young adults.