Evaluating the Strength of Association of Human Papillomavirus Infection With Penile Carcinoma: A Meta-Analysis

Background Human papillomavirus (HPV) is a common sexually transmitted infection that is strongly associated with cervical cancer. A link to penile cancers has been suggested by case series. We sought to assess the strength of the association between HPV infection and penile cancer by meta-analysis. Methods A literature search to identify population-based studies evaluating the risk of HPV infection with penile cancer was conducted via PubMed and Google Scholar databases through December 2020. Studies were included in the pooled analyses if they presented relative risk (RR) estimates comparing penile cancer cases with noncases by HPV exposure status. They were stratified by (1) type of HPV, (2) test used to determine past HPV infection, and (3) the penile cancer type. Pooled analyses were conducted for stratum with at least 2 independent studies using fixed-effects and random-effects models. Results Fourteen articles representing 9 study populations fit the inclusion criteria and were included in the pooled analysis. Based on these studies, the pooled RRs are 2.9 (95% confidence interval [CI], 1.7–5.0; n = 4 studies) for invasive penile cancer and seropositivity to HPV16 L1, 4.5 (95% CI, 1.3–15.5; n = 2) for seropositivity to HPV18, and 8.7 for anogenital warts (95% CI, 5.1–14.8; n = 5). For the 3 studies reporting invasive and in situ penile cancer, the risk was 7.6 for anogenital warts. Conclusions The pooled RRs indicate up to a 4.5-fold increased risk between seropositivity for HPV infection and invasive penile cancer. This is much lower than associations seen between HPV and cervical cancer.