The relationship between human papillomavirus and penile cancer over the past decade: a systematic review and meta-analysis

Human papillomavirus (HPV) infection appears to play an important role in the development of penile cancer (PeCa), but their relationship remains unclear. Therefore, we performed a systematic review and meta-analysis to elucidate their relationship. We systematically searched Embase, PubMed, Cochrane Library, and Web of Science for case-control studies and cross-sectional studies using polymerase chain reaction (PCR) technology on formalin-fixed paraffin-embedded (FFPE) or paraffin-embedded (PE) PeCa tissues to detect HPV (published between January 1, 2007, and December 29, 2017; no language restrictions). Twenty-two studies were identified, and 1664 cases were available for analysis. The combined HPV infectious risk of PeCa is 51.0% (95% confidence interval [CI]: 43.0%–60.0%). The three most common subtypes of HPV were HPV16 (28.5%), HPV18 (2.3%), and HPV6 (2.3%). The virus was relevantly associated with basaloid (85.5%, 95% CI: 77.2%–93.8%) and warty (50.0%, 95% CI: 35.2%–64.8%) carcinomas. The invasiveness of PeCa was not associated with HPV (χ(2) = 0.181, df = 1, P < 0.671). HPV infection in PeCa tended to be moderately differentiated (54.4%, 95% CI: 47.7%–61.1%). This study found that almost half of PeCa patients are associated with HPV. The most commonly associated genotype is HPV16, but several other genotypes were also detected. In addition to types 6 and 11, other single low-risk HPV infections have been found to contribute to PeCa to a lesser degree. HPV-positive tumors tend to exhibit warty and/or basaloid features, corresponding to a moderate histological grade. The role of HPV in PeCa should be revisited to provide evidence for the development of PeCa in the presence of HPV infection.